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篠山 大明  ササヤマ ダイメイ

教員組織学術研究院(医学系)電話番号
教育組織医学部 医学科 精神医学FAX番号
職名准教授メールアドレス
住所〒390-8621 長野県松本市旭3-1-1ホームページURL

プロフィール

研究分野
キーワード:自閉スペクトラム症
現在の研究課題
自閉症
キーワード:自閉スペクトラム症 , 神経発達症
所属学会
所属学会
信州精神神経学会
学歴
出身大学院
2013 , 信州大学大学院 , 医学系研究科 , 医学系
2004 , 信州大学 , 医学部 , 医学科
1998 , 東京大学 , 理学部 , 地球惑星物理学科

出身学校・専攻等(大学院を除く)
2004 , 信州大学 , 医学部 , 医学科
1998 , 東京大学 , 理学部 , 地球惑星物理学科

取得学位
博士(医学) , 信州大学

免許・資格等
2004 , 医師免許

研究活動業績

研究業績(著書・
発表論文等)
書籍等出版物
Trait Loci Mapping and CSF Proteome, Methods Mol Biol. 2044 , 365-376
2019
Author:Sasayama D, Hattori K, Kunugi H.


論文
Improvement of catatonia-induced rapid respiratory failure with electroconvulsive therapy: A case report.
Asian journal of psychiatry,78:103280-103280 2022(Oct. 06)
Author:Toshinori Nakamura; Misaki Shimizu-Ichikawa; Kazuhito Takahashi; Sari Shimizu; Takashi Ichiyama; Keisuke Todoroki; Masataka Konno; Daisuke Amada; Daimei Sasayama; Shinsuke Washizuka
Abstract:We encountered a case of sudden respiratory failure during treatment of catatonia that required intensive care. Electroconvulsive therapy (ECT) was administered in the intensive care unit while the patient was under systemic control. The catatonia symptom was relieved, and respiratory failure improved. Although a proximal venous thrombus was observed, anticoagulation therapy was continued during ECT, and the patient was successfully treated without causing a pulmonary embolism. It is crucial to monitor the patient's physical and psychological symptoms because respiratory status may deteriorate rapidly in a catatonic state.


Altered levels of salivary cytokines in patients with major depressive disorder.
Clinical neurology and neurosurgery,221:107390-107390 2022(Oct.)
Author:Sumie Yui; Daimei Sasayama; Masaki Yamaguchi; Shinsuke Washizuka
Abstract:OBJECTIVE: Accumulating evidence indicate the involvement of inflammation in the pathogenesis of mental disorders. Numerous studies have shown that proinflammatory cytokines were elevated in peripheral blood of patients with major depressive disorder (MDD). A few recent research have explored the possibility of using saliva as a biomarker for depressive symptoms. The objective of this study is to examine the salivary cytokine levels in patients with MDD and healthy controls. METHODS: Participants were 19 patients with MDD and 50 healthy controls. The levels of 27 cytokines in saliva were measured by multiplex bead array assay. RESULTS: The Mann-Whitney U-test showed that the levels of IL-1β, IL-6, IL-9, IL-12p70, IL-13, Chemokine CCL11 (Eotaxin), MIP-1α, RANTES, and VEGF were significantly higher in patients than controls. The quantile regression analysis showed that IL-1β, IL-12p70, CCL11, and VEGF remained significant after controlling for possible confounding factors. CONCLUSION: The findings were in line with previous studies that showed elevated peripheral levels of cytokines in patients with MDD. Our present data provide preliminary support for altered salivary cytokine levels in patients with MDD and suggest that salivary cytokines may serve as a novel target for elucidating the pathophysiology underlying MDD.


Trends in Diagnosed Attention-Deficit/Hyperactivity Disorder Among Children, Adolescents, and Adults in Japan From April 2010 to March 2020.
JAMA network open,5(9):e2234179 2022(Sep. 01)
Author:Daimei Sasayama; Rie Kuge; Yuki Toibana; Hideo Honda


Twenty-year longitudinal birth cohort study of individuals diagnosed with autism spectrum disorder before seven years of age.
Journal of child psychology and psychiatry, and allied disciplines 2022(Apr. 11)
Author:Mitsuaki Iwasa; Yasuo Shimizu; Daimei Sasayama; Miho Imai; Hiroko Ohzono; Miori Ueda; Ikuko Hara; Hideo Honda
Abstract:BACKGROUND: Previous longitudinal studies have demonstrated that psychosocial outcomes for autistic adults are very limited. However, most studies are clinic-based and liable to selection bias and major methodological problems. METHODS: We conducted a long-term follow-up study with 278 autistic individuals from our previous birth cohort study comprising 31,426 individuals. All participants were born in northern Yokohama between 1988 and 1996, diagnosed with autism spectrum disorder (ASD) by age seven, and followed up over 20 years. A total of 170 consented to participate in the study. Outcome measures included overall social functioning based on work, independent living, and friendships. Moreover, the time-use data concerning social participation and activities of daily living were compared with the general population. RESULTS: Psychosocial outcomes in adulthood (average age 25) were very good in 13.7%, good in 25.0%, fair in 31.0%, poor in 25.6%, and very poor in 4.8% of the participants. The majority participated in major life areas of and work and education (96.4%), sports (82.1%), and recreational activities and/or hobbies (98.8%). The proportion of participants who engaged in housework and self-care was comparable to that of the general population. Participants with IQ < 50 at age five had significantly worse outcomes than those with higher IQ; however, for those with IQ ≥ 50, outcomes were not significantly associated with IQ levels. CONCLUSIONS: Although complete independence was difficult to accomplish, many autistic adults engaged in organized community activities and housework and self-care. Time-use survey could offer a variety of data in investigating psychosocial outcomes of ASD cross-culturally.


Psychological Distress and Personality Dimensions Associated with Romantic Orientation Among Japanese Adults.
LGBT health 2022(Jan. 04)
Author:Daimei Sasayama; Miyuki Chijiiwa; Shun Nogawa; Kenji Saito; Hiroshi Kunugi
Abstract:Purpose: Evidence is scarce regarding the associations of romantic orientation with mental health and personality. The aims of the present study, therefore, were to examine psychological distress among homoromantic, biromantic, and heteroromantic adults and to investigate how personality dimensions influence their distress. Methods: A cross-sectional survey study was conducted between August 2018 and January 2021. Psychological distress, personality, and romantic orientation were assessed with the 6-item Kessler Psychological Distress Scale (K6), the Ten-Item Personality Inventory (TIPI), and a question about romantic orientation, respectively, in a web-based survey distributed to 11,922 participants. Saliva samples were collected for DNA extraction. After excluding those who did not cluster with Japanese ancestry and those whose genotypic sex did not match their reported sex, 11,662 individuals were included in further analyses. Results: The prevalence of being homoromantic or biromantic was 1.0% and 2.0% for females and 1.5% and 1.2% for males, respectively. Homoromantic males, but not females, had significantly higher K6 scores than their heteroromantic counterparts. Both male and female biromantic participants had significantly higher K6 scores than their heteroromantic counterparts. Furthermore, a significant association was found between romantic orientation and TIPI scores. Accounting for personality profiles did not alter the observed association between romantic orientation and psychological distress. Conclusion: Biromantic adults and homoromantic male adults of genetically confirmed Japanese ancestry living in Japan experienced higher psychological distress than heteroromantic individuals. The mental health disparities of the romantic minority individuals were irrespective of their personality profiles, suggesting the involvement of other factors such as minority stress in Japan.


Improved response to electroconvulsive therapy after switching from haloperidol to blonanserin in a patient with treatment-resistant schizophrenia.
Psychiatry and clinical neurosciences 2021(Dec. 18)
Author:Kazuhito Takahashi; Saeko Yokotsuka-Ishida; Toshinori Nakamura; Daimei Sasayama; Shinsuke Washizuka


Reduced functional connectivity in the prefrontal cortex of elderly catatonia patients: A longitudinal study using functional near-infrared spectroscopy
NEUROSCIENCE RESEARCH,170:322-329 2021(Sep.)
Author:Nakamura, Toshinori; Sasayama, Daimei; Hagiwara, Tetsuya; Kito, Hisashi; Washizuka, Shinsuke


Hyperactive/impulsive symptoms and autistic trait in institutionalized children with maltreatment experience.
New directions for child and adolescent development,2021(179):29-39 2021(Sep.)
Author:Junko Imai; Daimei Sasayama; Rie Kuge; Hideo Honda; Shinsuke Washizuka
Abstract:The present study examined how maltreatment experience was associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) symptoms in children under institutional care. The key caregivers of children and adolescents aged 6 to 18 years who were under institutional care in Nagano prefecture, Japan were asked to answer the background questionnaire, ADHD-Rating Scale, and the Japanese children's version of the Autism-Spectrum Quotient. A total of 378 valid responses were obtained, of which 222 reported maltreatment experience prior to institutionalization. Both hyperactive/impulsive and inattentive scores were significantly higher in the maltreated group. Maltreatment experience was significantly associated with the presence of hyperactive/impulsive symptoms (p = 0.003) and inattentive symptoms (p = 0.027). Particularly, those who had experienced physical abuse were significantly more likely to have hyperactive/impulsive symptoms (p = 0.012) and autistic trait (p = 0.002). Thorough assessment of neurodevelopmental symptoms should be performed when placing children with maltreatment experience into institutional care.


Trends in Autism Spectrum Disorder Diagnoses in Japan, 2009 to 2019.
JAMA network open,4(5):e219234 2021(May 03)
Author:Daimei Sasayama; Rie Kuge; Yuki Toibana; Hideo Honda
Abstract:JAMA NETWORK OPEN


Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans
METABOLITES,11(5):--268 2021(May)
Author:Saito, Kosuke; Hattori, Kotaro; Hidese, Shinsuke; Sasayama, Daimei; Miyakawa, Tomoko; Matsumura, Ryo; Tatsumi, Megumi; Yokota, Yuuki; Ota, Miho; Hori, Hiroaki; Kunugi, Hiroshi
Abstract:METABOLITES


Brief Report: Cumulative Incidence of Autism Spectrum Disorder Before School Entry in a Thoroughly Screened Population
J Autism Dev Disord,51(4):1400-1405 2021(Apr.)
Author:Sasayama D, Kudo T, Kaneko W, Kuge R, Koizumi N, Nomiyama T, Washizuka S, Honda H.
Abstract:J Autism Dev Disord


Possible utilization of salivary IFN-γ/IL-4 ratio as a marker of chronic stress in healthy individuals
Neuropsychopharmacol Rep,41(1):65-72 2021(Mar.)
Author:Takemori Y, Sasayama D, Toida Y, Kotagiri M, Sugiyama N, Yamaguchi M, Washizuka S, Honda H
Abstract:Neuropsychopharmacol Rep


Sex differences in serum levels of 5α-androstane-3β, 17β-diol, and androstenediol in the young adults: A liquid chromatography-tandem mass spectrometry study.
PloS one,16(12):e0261440 2021
Author:Haruka Tanabe; Hitoshi Mutai; Daimei Sasayama; Hidehiko Sasamoto; Yoshimichi Miyashiro; Nobuhiro Sugiyama; Shinsuke Washizuka
Abstract:Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERβ include 5α-androstane-3β, 17β-diol (3βAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3βAdiol and Δ5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17β-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3βAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3βAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3βAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3βAdiol and E2 levels, not by Δ5-diol level.


ORTHOSTATIC HYPOTENSION: UNCOMMON SIDE EFFECT OF ARIPIPRAZOLE
PSYCHIATRIA DANUBINA,33(1):63-64 2021
Author:Takahashi, Kazuhito; Nakamura, Toshinori; Sasayama, Daimei; Washizukac, Shinsuke
Abstract:PSYCHIATRIA DANUBINA


Cerebrospinal Fluid Inflammatory Cytokine Levels in Patients With Major Psychiatric Disorders: A Multiplex Immunoassay Study
FRONTIERS IN PHARMACOLOGY,11:- 2021
Author:Hidese, Shinsuke; Hattori, Kotaro; Sasayama, Daimei; Tsumagari, Takuya; Miyakawa, Tomoko; Matsumura, Ryo; Yokota, Yuuki; Ishida, Ikki; Matsuo, Junko; Yoshida, Sumiko; Ota, Miho; Kunugi, Hiroshi
Abstract:FRONTIERS IN PHARMACOLOGY


Lower cerebrospinal fluid CRH concentration in chronic schizophrenia with negative symptoms
JOURNAL OF PSYCHIATRIC RESEARCH,127:13-19 2020(Aug.)
Author:Ishiwata, Sayuri; Hattori, Kotaro; Hidese, Shinsuke; Sasayama, Daimei; Miyakawa, Tomoko; Matsumura, Ryo; Yokota, Yuuki; Yoshida, Sumiko; Kunugi, Hiroshi
Abstract:JOURNAL OF PSYCHIATRIC RESEARCH


Increased apolipoprotein E and decreased TNF-α in the cerebrospinal fluid of nondemented APOE-ε4 carriers
Neuropsychopharmacol Rep.,40(2):201-205 2020(Jun.)
Author:Sasayama D, Hattori K, Yokota Y, Matsumura R, Teraishi T, Yoshida S, Kunugi H.
Abstract:Neuropsychopharmacol Rep.


Cerebrospinal fluid neuroplasticity-associated protein levels in patients with psychiatric disorders: a multiplex immunoassay study
TRANSLATIONAL PSYCHIATRY,10(1):--161 2020
Author:Hidese, Shinsuke; Hattori, Kotaro; Sasayama, Daimei; Tsumagari, Takuya; Miyakawa, Tomoko; Matsumura, Ryo; Yokota, Yuuki; Ishida, Ikki; Matsuo, Junko; Yoshida, Sumiko; Ota, Miho; Kunugi, Hiroshi
Abstract:TRANSLATIONAL PSYCHIATRY


Possible association between photic sneeze syndrome and migraine and psychological distress.
Neuropsychopharmacol Rep.,39(3):217-222 2019(Sep.)
Author:Sasayama D, Asano S, Nogawa S, Takahashi S, Saito K, Kunugi H.
Abstract:Neuropsychopharmacol Rep.


Associations of Autism Spectrum Quotient and Personality Profiles with Eating Behaviors in Patients with Anorexia Nervosa and in a Non-clinical Population
信州医学雑誌,67(3):157-166 2019(Jun.)
Author:Takahashi-Asai, Yuka; Sasayama, Daimei; Sugiyama, Nobuhiro; Maruyama, Fumi; Washizuka, Shinsuke
Abstract:信州医学雑誌


Lysophosphatidic acid levels in cerebrospinal fluid and plasma samples in patients with major depressive disorder
Heliyon,5(5):e01699-e01699 2019(May)
Author:Leo Gotoh; Misa Yamada; Kotaro Hattori; Daimei Sasayama; Takamasa Noda; Sumiko Yoshida; Hiroshi Kunugi; Mitsuhiko Yamada


Levels of lysophosphatidic acid in cerebrospinal fluid and plasma of patients with schizophrenia.
Psychiatry research,273:331-335 2019(Mar.)
Author:Leo Gotoh; Misa Yamada; Kotaro Hattori; Daimei Sasayama; Takamasa Noda; Sumiko Yoshida; Hiroshi Kunugi; Mitsuhiko Yamada
Abstract:It is suggested that lysophosphatidic acid (LPA) plays a key role in the pathophysiology of schizophrenia. In this study, we measured LPA levels by enzyme-linked immunosorbent assay in cerebrospinal fluid (CSF) and plasma samples. The participants were 49 patients with schizophrenia and 49 normal healthy controls for CSF study, and 42 patients and 44 controls for plasma study. We found that LPA levels in the patients were not significantly different from those of controls in CSF (controls: 0.189 ± 0.077 µM, patients: 0.175 ± 0.067 µM; P = 0.318) and plasma samples (controls: 0.131 ± 0.067 µM, patients: 0.120 ± 0.075 µM; P = 0.465). On the other hand, CSF levels in medicated patients (0.162 ± 0.061 µM) were significantly lower than those observed in unmedicated patients (0.224 ± 0.067 µM, P = 0.038), suggesting that our findings could be masked by the influence of medication with antipsychotics. Interestingly, we detected significant negative correlation between PANSS scores and plasma LPA levels, especially in males and in unmedicated patients. Our result suggests that LPA levels in CSF and plasma samples would not serve as a diagnostic biomarker, but plasma levels could be used for symptomatic assessment of schizophrenia.


Trait Loci Mapping and CSF Proteome.
Methods in molecular biology (Clifton, N.J.),2044:365-376 2019
Author:Daimei Sasayama; Kotaro Hattori; Hiroshi Kunugi
Abstract:Recent advance in high-throughput proteome analysis has enabled genome-wide and proteome-wide analyses of associations between single nucleotide polymorphisms and protein expression levels. Protein quantitative trait locus (pQTL) studies using cerebrospinal fluid (CSF) and DNA samples may provide valuable insights into the genetic basis and molecular mechanisms regulating protein expression in the central nervous system. In this chapter, we describe a step-by-step procedures of CSF collection and pQTL analysis, by using PLINK and R software.


中村和彦(編)『児童・青年期精神疾患の薬物治療ガイドライン』
児童青年精神医学とその近接領域,60(3):376-377 2019
Author:篠山 大明
Abstract:児童青年精神医学とその近接領域


Reduced plasma orexin-A levels in patients with bipolar disorder.
Neuropsychiatric disease and treatment,15:2221-2230 2019
Author:Shoko Tsuchimine; Kotaro Hattori; Miho Ota; Shinsuke Hidese; Toshiya Teraishi; Daimei Sasayama; Hiroaki Hori; Takamasa Noda; Sumiko Yoshida; Fuyuko Yoshida; Hiroshi Kunugi
Abstract:Purpose: Orexins are hypothalamic neuropeptides involved in the regulation of sleep, appetite and arousal. An altered orexin system has been implicated in the pathophysiology of psychiatric disorders. This study aimed to examine whether plasma orexin-A levels differ in patients with schizophrenia, major depressive disorder (MDD), or bipolar disorder (BD) compared to in healthy controls. We also examined the possible correlations between plasma orexin-A levels and clinical variables. Patients and methods: All participants were Japanese. The sample consisted of 80 patients with schizophrenia (42 women, 52.5%; mean age 36.8 years), 80 patients with MDD (43 women, 53.8%; 43.7 years), and 40 patients with BD (24 women, 60%; 41.1 years), as well as 80 healthy controls (48 women, 60%; 47.0 years). Plasma orexin-A levels were quantified by an enzyme-linked immunosorbent assay. Results: Mean orexin-A levels were significantly different across the four diagnostic groups (F=4.09; df=3; p=0.007, η2 =0.06). In particular, the patients with BD showed significantly lower orexin-A levels than did the controls. When the median value of the control group (109.8 pg/ml) was set as a cut-off value, subjects whose orexin-A levels were below the cut-off were more common in all psychiatric groups (schizophrenia: 73.8%, x2 =9.56, df=1, p=0.003, OR=2.81, 95% CI: 1.45 to 5.45, d=0.57; MDD: 78.5%, x2 =14.02, df=1, p<0.001, OR=3.65, 95% CI: 1.82 to 7.29, d=0.72; BD: 87.5%, x2 =16.0, df=1, p<0.001, OR=7.00, 95% CI: 2.49 to 19.70, d=1.07). We found no association between plasma orexin-A levels and any clinical symptoms, depression severity, or medication doses. Conclusion: Our results suggest that plasma orexin-A levels are reduced in patients with BD.


Integrated profiling of phenotype and blood transcriptome for stress vulnerability and depression.
Journal of psychiatric research,104:202-210 2018(Sep.)
Author:Hori H; Nakamura S; Yoshida F; Teraishi T; Sasayama D; Ota M; Hattori K; Kim Y; Higuchi T; Kunugi H
Abstract:Etiology of depression and its vulnerability remains elusive. Using a latent profile analysis on dimensional personality traits, we previously identified 3 different phenotypes in the general population, namely stress-resilient, -vulnerable, and -resistant groups. Here we performed microarray-based blood gene expression profiling of these 3 groups (n = 20 for each group) in order to identify genes involved in stress vulnerability as it relates to the risk of depression. Identified differentially expressed genes among the groups were most markedly enriched in ribosome-related pathways. These ribosomal genes, which included ribosomal protein L17 (RPL17) and ribosomal protein L34 (RPL34), were upregulated in relation to the stress vulnerability. Protein-protein interaction and correlational co-expression analyses of the differentially expressed genes/non-coding RNAs consistently showed that functional networks involving ribosomes were affected. The significant upregulation of RPL17 and RPL34 was also observed in depressed patients compared to healthy controls, as confirmed in 2 independent case-control datasets by using pooled microarray data and qPCR experiments (total number of subjects was 122 and 166, respectively). Moreover, the upregulation of RPL17 and RPL34 was most marked in DSM-IV major depressive disorder, followed by in bipolar disorder, and then in schizophrenia, suggesting some diagnostic specificity of these markers as well as their general roles in stress vulnerability. These results suggest that ribosomal genes, particularly RPL17 and RPL34, can play integral roles in stress vulnerability and depression across nonclinical and clinical conditions. This study presents an opportunity to understand how multiple psychological traits and underlying molecular mechanisms interact to render individuals vulnerable to depression.


Association of depression with body mass index classification, metabolic disease, and lifestyle: A web-based survey involving 11,876 Japanese people
Journal of Psychiatric Research,102:23-28 2018(Jul. 01)
Author:Shinsuke Hidese; Shinya Asano; Kenji Saito; Daimei Sasayama; Hiroshi Kunugi
Abstract:Body mass index (BMI) and lifestyle-related physical illnesses have been implicated in the pathology of depression. We aimed to investigate the association of depression wih BMI classification (i.e., underweight, normal, overweight, and obese), metabolic disease, and lifestyle using a web-based survey in a large cohort. Participants were 1000 individuals who have had depression (mean age: 41.4 ± 12.3 years, 501 men) and 10,876 population-based controls (45.1 ± 13.6 years, 5691 men). The six-item Kessler scale (K6) test was used as a psychological distress scale. Compared to in the controls, obesity and hyperlipidemia were more common and frequency of a snack or night meal consumption was higher, whereas frequencies of breakfast consumption and vigorous and moderate physical activities were lower in the patients. K6 test scores were higher for underweight or obese people compared to normal or overweight people. A logistic regression analysis showed that the K6 test cut-off score was positively associated with being underweight, hyperlipidemia, and the frequency of a snack or night meal consumption, whereas it was negatively associated with the frequency of breakfast consumption in the patients. Logistic regression analyses showed that self-reported depression was positively associated with metabolic diseases and the frequency of a snack or night meal consumption, whereas it was negatively associated with the frequency of breakfast consumption. The observed associations of depression with BMI classification, metabolic disease, and lifestyle suggest that lifestyle and related physical conditions are involved in at least a portion of depressive disorders.


Manual dexterity and brain structure in patients with schizophrenia: A whole-brain magnetic resonance imaging study
Psychiatry Research - Neuroimaging,276:9-14 2018(Jun. 30)
Author:Shinsuke Hidese; Miho Ota; Daimei Sasayama; Junko Matsuo; Ikki Ishida; Moeko Hiraishi; Toshiya Teraishi; Kotaro Hattori; Hiroshi Kunugi
Abstract:The Purdue Pegboard Test (PPT) is a motor coordination task used to assess manual dexterity. Although several brain regions are thought to be involved in PPT performance, the relationship of the task with decreased insular volume has not been investigated. The PPT was administered to 83 subjects diagnosed with schizophrenia (mean ± standard deviation age: 38.6 ± 11.2 years 47 males, 36 females) and 130 healthy controls (42.1 ± 15.2 years 67 males, 63 females). All subjects were Japanese and right-handed. Gray matter volume was analyzed using voxel-based morphometry in statistical parametric mapping, while white matter measures were analyzed using diffusion tensor imaging in tract-based spatial statistics. For the patients with schizophrenia, the left-hand scores positively correlated with the right insular and bilateral operculum volumes, while the summation score (sum of left-, right-, and both-hands scores) positively correlated with the right insular volume, and the summation and assembly (number of assemblies completed) scores correlated with the diffuse white matter fractional anisotropy, axial diffusivity, and radial diffusivity values. In contrast, no significant correlations were found for the controls. These results suggested that decreased insular volume and white matter measures contributed to the impairments in manual dexterity observed in subjects with schizophrenia.


A genome-wide association study on photic sneeze syndrome in a Japanese population
Journal of Human Genetics,63(6):765-768 2018(Jun. 01)
Author:Daimei Sasayama; Shinya Asano; Shun Nogawa; Shoko Takahashi; Kenji Saito; Hiroshi Kunugi
Abstract:Photic sneeze syndrome (PSS) is characterized by a tendency to sneeze when the eye is exposed to bright light. Recent genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) associated with PSS in Caucasian populations. We performed a GWAS on PSS in Japanese individuals who responded to a web-based survey and provided saliva samples. After quality control, genotype data of 210,086 SNPs in 11,409 individuals were analyzed. The overall prevalence of PSS was 3.2%. Consistent with previous reports, SNPs at 3p12.1 were associated with PSS at genome-wide significance (p < 5.0 × 10-8). Furthermore, two novel loci at 9q34.2 and 4q35.2 reached suggestive significance (p < 5.0 × 10-6). Our data also provided evidence supporting the two additional SNPs on 2q22.3 and 9q33.2 reportedly associated with PSS. Our study reproduced previous findings in Caucasian populations and further suggested novel PSS loci in the Japanese population.


Low cocaine- and amphetamine-regulated transcript (CART) peptide levels in human cerebrospinal fluid of major depressive disorder (MDD) patients
Journal of Affective Disorders,232:134-138 2018(May 01)
Author:Hyung Shin Yoon; Kotaro Hattori; Daimei Sasayama; Hiroshi Kunugi
Abstract:Background: Cocaine- and amphetamine-regulated transcript (CART) peptide is a candidate neuropeptide as a biomarker for major depressive disorder (MDD) because of its effects on emotion and distribution covering brain areas involved in the pathophysiology of MDD symptoms. However, it is unknown whether CART peptide levels are altered in the cerebrospinal fluid (CSF) of patients with MDD patients and are correlated with MDD symptoms. Methods: Subjects were 24 patients with MDD and 25 healthy controls matched for age, gender and ethnicity (Japanese). We measured CSF CART levels by a commercially available immunoassay kit and analyzed the relationships of the levels with antidepressant dose and symptoms assessed with the 21 item Hamilton Depression Rating Scale (HAMD-21). Results: CSF CART levels were significantly decreased in the patients than in the controls (p < 0.05). In MDD patient group, the CART levels had a negative correlation with antidepressant dose (imipramine-equivalent dose) (ρ = −0.55, p < 0.01) and significantly decreased in antidepressant-treated group (AD-treated group) compared to controls (p < 0.05). CSF CART levels showed significant negative correlations with psychomotor retardation, somatic anxiety, and general somatic symptoms (all p < 0.05) and a positive correlation with obsessive and compulsive symptoms (p < 0.05). Limitations: In our analysis, all classes of antidepressants were combined together and the effects of medication use in a longitudinal manner did not confirm. Conclusions: We report for the first time that CSF CART peptide levels are reduced in patients with MDD compared with healthy controls. The CART levels showed negative correlations with antidepressant dose and some symptoms, supporting the possibility that CART peptide is involved in the development of depressive symptoms.


13C-phenylalanine breath test and serum biopterin in schizophrenia, bipolar disorder and major depressive disorder
Journal of Psychiatric Research,99:142-150 2018(Apr. 01)
Author:Toshiya Teraishi; Masahiro Kajiwara; Hiroaki Hori; Daimei Sasayama; Shinsuke Hidese; Junko Matsuo; Ikki Ishida; Yasuhiro Kajiwara; Yuji Ozeki; Miho Ota; Kotaro Hattori; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Phenylalanine is required for the synthesis of the neurotransmitters dopamine, noradrenaline, and adrenaline. The rate-limiting step for phenylalanine metabolism is catalyzed by phenylalanine hydroxylase (PAH) and its cofactor tetrahydrobiopterin. We aimed to detect altered phenylalanine metabolism in major psychiatric disorders using the L-[1-13C]phenylalanine breath test (13C-PBT) and serum biopterin levels. We also investigated association of PAH mutations with schizophrenia and phenylalanine metabolism. 13C-phenylalanine (100 mg) was orally administered, and the breath 13CO2/12CO2 ratio was monitored for 120 min in four groups: 103 patients with schizophrenia (DSM-IV), 39 with bipolar disorder, 116 with major depressive disorder (MDD), and 241 healthy controls. Serum biopterin levels were measured by high performance liquid chromatography. Mutation screening of PAH exons was performed by direct sequencing in 46 schizophrenia patients. Association analysis was performed using six tag single nucleotide polymorphisms and the PAH Arg53His mutation by TaqMan assays in 616 schizophrenia patients and 1194 healthy controls. Analyses of covariance controlling for age, sex, and body weight showed that the index for the amount of exhaled 13CO2 was significantly lower in the schizophrenia group than in the other three groups (all p < 0.05). Biopterin levels in schizophrenia and MDD were significantly lower than those in controls. Biopterin levels correlated with 13C-PBT indices in controls. PAH polymorphisms were not associated with schizophrenia or 13C-PBT indices. 13C-PBT revealed reduced phenylalanine metabolism in schizophrenia, though we obtained no evidence of involvement of PAH polymorphism. Serum biopterin levels were lower in schizophrenia and MDD, warranting further investigation.


Increased cerebrospinal fluid complement C5 levels in major depressive disorder and schizophrenia
Biochemical and Biophysical Research Communications,497(2):683-688 2018(Mar. 04)
Author:Takashi Ishii; Kotaro Hattori; Tomoko Miyakawa; Kentaro Watanabe; Shinsuke Hidese; Daimei Sasayama; Miho Ota; Toshiya Teraishi; Hiroaki Hori; Sumiko Yoshida; Akihiko Nunomura; Kazuyuki Nakagome; Hiroshi Kunugi
Abstract:Inflammation has been implicated in a variety of psychiatric disorders. We aimed to determine whether levels of complement C5 protein in the cerebrospinal fluid (CSF), which may reflect activation of the complement system in the brain, are altered in patients with major psychiatric disorders. Additionally, we examined possible associations of CSF C5 levels with clinical variables. Subjects comprised 89 patients with major depressive disorder (MDD), 66 patients with bipolar disorder (BPD), 96 patients with schizophrenia, and 117 healthy controls, matched for age, sex, and ethnicity (Japanese). Diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. CSF C5 levels were measured by enzyme-linked immunosorbent assay. CSF C5 levels were significantly increased in the patients with MDD (p < 0.001) and in the patients with schizophrenia (p = 0.001), compared with the healthy controls. The rate of individuals with an “abnormally high C5 level” (i.e., above the 95th percentile value of the control subjects) was significantly increased in all psychiatric groups, relative to the control group (all p < 0.01). Older age, male sex, and greater body mass index tended to associate with higher C5 levels. There was a significantly positive correlation between C5 levels and chlorpromazine-equivalent dose in the patients with schizophrenia. Thus, we found, for the first time, elevated C5 levels in the CSF of patients with major psychiatric disorders. Our results suggest that the activated complement system may contribute to neurological pathogenesis in a portion of patients with major psychiatric disorders.


Plasma amino acid profile in major depressive disorder: Analyses in two independent case-control sample sets
Journal of Psychiatric Research,96:23-32 2018(Jan. 01)
Author:Shintaro Ogawa; Norie Koga; Kotaro Hattori; Junko Matsuo; Miho Ota; Hiroaki Hori; Daimei Sasayama; Toshiya Teraishi; Ikki Ishida; Fuyuko Yoshida; Sumiko Yoshida; Takamasa Noda; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Some amino acids act as neurotransmitters themselves, or are precursors of neurotransmitters. Previous studies reported inconsistent results regarding their changes in blood in major depressive disorder (MDD), which prompted us to examine plasma levels of amino acids and related molecules in two independent case-control sample sets. In total, 511 subjects were recruited. Sample set A consisted of 164 patients with MDD (147 currently depressed [dMDD] 17 in remission, DSM-IV) and 217 healthy controls. Sample set B consisted of 65 patients (51 dMDD 14 in remission) and 65 controls. Plasma amino acid levels were measured using high-performance liquid chromatography for set A and liquid chromatography/mass spectrometry for set B. We further analyzed the relationships between plasma amino acid levels and clinical variables. In sample set A, plasma asparagine, histidine+1-methylhistidine, methionine, phenylalanine, tryptophan, and tyrosine levels were decreased, while plasma glutamate and phosphoethanolamine were elevated in dMDD compared to controls (all P < 0.0005), even after correcting for multiple testing. Plasma leucine levels were associated with “psychic anxiety.” In sample set B, glutamate and methionine levels were also altered in the same direction to that in sample set A (both P < 0.05). In the integrative analysis, plasma glutamate and methionine levels were found to be significantly associated with the diagnosis of MDD with small to medium effect sizes (both P < 1.0E-6). In conclusion, several amino acids and related molecules were altered in patients with MDD. Decreased methionine and increased glutamate levels were found consistently in the two sample sets, suggesting their involvement in MDD. Further investigations are warranted on the possible role of amino acids in the pathophysiology of MDD.


Cerebrospinal fluid D-serine concentrations in major depressive disorder negatively correlate with depression severity
JOURNAL OF AFFECTIVE DISORDERS,226:155-162 2018(Jan.)
Author:Sayuri Ishiwata; Kotaro Hattori; Daimei Sasayama; Toshiya Teraishi; Tomoko Miyakawa; Yuuki Yokota; Ryo Matsumura; Toru Nishikawa; Hiroshi Kunugi
Abstract:Background: D-serine is an endogenous co-agonist of N-methyl-D-aspartate receptor (NMDAR) and plays an important role in glutamate neurotransmission. Several studies suggested the possible involvement of D-serine related in the pathophysiology of psychiatric disorders including major depression disorders (MDD). We tried to examine whether cerebrospinal fluid (CSF) or plasma D-serine concentrations are altered in MDD and whether D-serine concentrations correlated with disease severity. Methods: 26 MDD patients and 27 healthy controls matched for age, sex and ethnicity were enrolled. We measured amino acids in these samples using by high-performance liquid chromatography with fluorometric detection. Results: D-serine and L-serine, precursor of D-serine, levels in CSF or plasma were not significantly different in patients of MDD compared to controls. Furthermore, a significant correlation between D-serine levels in CSF and Hamilton Depression Rating Scale (HAMD)-17 score was observed (r = -0.65, p = 0.006). Furthermore, we found a positive correlation between CSF D-serine and HVA concentrations in MDD patients (r = 0.54, p = 0.007). CSF D-serine concentrations were correlated with those of plasma in MDD (r = 0.61, p = 0.01) but not in controls. In CSF, we also confirmed a significant correlation between D-serine and L-serine levels in MDD (r = 0.72, p < 0.0001) and controls (r = 0.70, p < 0.0001). Conclusions: The study has some limitations; sample size was relatively small and most patients were medicated. We revealed that CSF D-serine concentrations were correlated with depression severity and HVA concentrations and further investigation were required to reveal the effect of medication and disease heterogeneity.


Association of body mass nindex-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population
ACTA NEUROPSYCHIATRICA,29(5):299-308 2017(Oct.)
Author:Midori Ninomiya-Baba; Junko Matsuo; Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Miho Ota; Kotaro Hattori; Takamasa Noda; Ikki Ishida; Shigenobu Shibata; Hiroshi Kunugi
Abstract:Objective: Obesity is a risk factor for psychiatric diseases. Recently, a number of single nucleotide polymorphisms (SNPs) have been shown to be related to body mass index (BMI). In this study, we investigated the association of BMI-related SNPs with psychiatric diseases and one of their endophenotypes, memory performance, in a Japanese population. Methods: The subjects were 1624 patients with one of three psychiatric diseases (799 patients with major depressive disorder, 594 with schizophrenia, and 231 with bipolar disorder) and 1189 healthy controls. Memory performance was assessed using the Wechsler Memory Scale Revised (WMS-R). Genomic DNA was prepared from venous blood and used to genotype 23 BMI-related SNPs using the TaqMan 5'-exonuclease allelic discrimination assay. We then analysed the relationships between the SNPs and psychiatric disease and various subscales of the WMS-R. Results: Three SNPs (rs11142387, rs12597579, and rs6548238) showed significant differences in the genotype or allele frequency between patients with any psychiatric diseases and controls. Furthermore, six SNPs (rs11142387, rs12597579, rs2815752, rs2074356, rs4776970, and rs2287019) showed significant differences in at least one subscale of the WMS-R depending on the genotypes of the healthy controls. Interestingly, rs11142387 near the Kruppel-like factor 9 (KLF9) was significantly associated with psychiatric disease and poor memory function. Conclusions: We identified three and six BMI-related SNPs associated with psychiatric disease and memory performance, respectively. In particular, carrying the A allele of rs11142387 near KLF9 was found to be associated with psychiatric disease and poor memory performance, which warrants further investigations.


Relationships of Cerebrospinal Fluid Monoamine Metabolite Levels With Clinical Variables in Major Depressive Disorder
JOURNAL OF CLINICAL PSYCHIATRY,78(8):E947-+ 2017(Sep.)
Author:Hyung Shin Yoon; Kotaro Hattori; Shintaro Ogawa; Daimei Sasayama; Miho Ota; Toshiya Teraishi; Hiroshi Kunugi
Abstract:Objective: Many studies have investigated cerebrospinal fluid (CSF) monoamine metabolite levels in depressive disorders. However, their clinical significance is still unclear. We tried to determine whether CSF monoamine metabolite levels could be a state-dependent marker for major depressive disorder (MDD) based on analyses stratified by clinical variables in a relatively large sample. Methods: Subjects were 75 patients with MDD according to DSM-IV criteria and 87 healthy controls, matched for age, sex, and ethnicity (Japanese). They were recruited between May 2010 and November 2013. We measured homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in CSF samples by high-performance liquid chromatography. We analyzed the relationships of the metabolite levels with age, sex, diagnosis, psychotropic medication use, and depression severity. Results: There was a weak positive correlation between age and 5-HIAA levels in controls (rho = 0.26, P < .016) and a similar trend in patients, while sex was unrelated to any metabolite. All monoamine metabolites in moderately to severely depressed patients (17-item Hamilton Depression Rating Scale score > 12) were significantly lower than those in controls (P < .0005 for all 3 metabolites). We found that antidepressants decreased the levels of 5-HIAA (rho = -0.39, P < .001) and MHPG (rho = -0.49, P < .0001) and that antipsychotics increased levels of HVA (rho = 0.24, P < .05). There was a strong correlation between HVA and 5-HIAA levels (controls: rho = 0.79, P = .000001; MDD: rho = 0.66, P = .000001). HVA levels (rho = -0.43, P < .001) and 5-HIAA levels (rho = -0.23, P < .05), but not MHPG levels (rho = -0.18, P > .1), were related to depression severity. Conclusions: CSF 5-HIAA and HVA levels could be state-dependent markers in MDD patients. Since 5-HIAA levels greatly decrease with the use of antidepressants, HVA levels might be more useful in the clinical setting. (C) Copyright 2017 Physicians Postgraduate Press, Inc.


Successful Readministration of Clozapine in a Patient With a History of Clozapine-Induced Elevation of Creatine Phosphokinase.
Primary Care Companion CNS Disorder,19(4) 2017(Aug.)
Author:Takahashi Y, Ogihara T, Sasayama D, Washizuka S.
Abstract:Primary Care Companion CNS Disorder


Plasma and cerebrospinal fluid G72 protein levels in schizophrenia and major depressive disorder
PSYCHIATRY RESEARCH,254:244-250 2017(Aug.)
Author:Sayuri Ishiwata; Kotaro Hattori; Daimei Sasayama; Toshiya Teraishi; Tomoko Miyakawa; Yuuki Yokota; Ryo Matsumura; Fuyuko Yoshida; Tom Nishikawa; Hiroshi Kunugi
Abstract:G72 is a modulator of D-amino acid oxidase, the enzyme that degrades n-serine, an amino acid that plays a critical role in glutamate neurotransmission, and has been implicated in psychiatric disorders. The aim of this study was to examine whether plasma or cerebrospinal fluid (CSF) G72 protein levels were altered in either schizophrenia or major depressive disorder (MDD) and whether any correlation between G72 levels and disease severity existed. Initially, 27 schizophrenic patients, 26 MDD patients, and 27 healthy controls matched for age, sex, and ethnicity were enrolled. Compared to those of controls, plasma or CSF G72 levels were not significantly different in patients with schizophrenia or MDD. Although we found a significant positive correlation between plasma G72 levels and a positive symptoms score on the positive and negative syndrome scale (PANSS), this was not replicated in the second study (40 schizophrenic patients). CSF G72 levels showed no significant correlation with PANSS scores. In MDD, neither plasma nor CSF G72 levels correlated significantly with depression severity. Since severity of our patients were relatively mild, further investigations in a large number of subjects including drug-free patients, younger patients, and more severely affected patients are warranted.


Novel oestrogen receptor beta-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice
SCIENTIFIC REPORTS,7:- 2017(Jul.)
Author:Daimei Sasayama; Nobuhiro Sugiyama; Shigeru Yonekubo; Akiko Pawlak; Hiroyasu Murasawa; Mie Nakamura; Morimichi Hayashi; Takashi Ogawa; Makoto Moro; Shinsuke Washizuka; Naoji Amano; Kazuhiro Hongo; Hideki Ohnota
Abstract:Hormonal changes due to menopause can cause various health problems including weight gain and depressive symptoms. Multiple lines of evidence indicate that oestrogen receptors (ERs) play a major role in postmenopausal obesity and depression. However, little is known regarding the ER subtype-specific effects on obesity and depressive symptoms. To delineate potential effects of ER beta activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor beta-selective ligand (C-1) in ovariectomized mice. Uterine weight, depressive behaviour, and weight gain were examined in sham-operated control mice and ovariectomized mice administered placebo, C-1, or 17 beta-oestradiol (E2). Administration of C-1 or E2 reduced body weight gain and depressive-like behaviour in ovariectomized mice, as assessed by the forced swim test. In addition, administration of E2 to ovariectomized mice increased uterine weight, but administration of C-1 did not result in a significant increase in uterine weight. These results suggest that the selective activation of ERa in ovariectomized mice may have protective effects against obesity and depressive-like behaviour without causing an increase in uterine weight. The present findings raise the possibility of the application of ER beta-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.


Cerebrospinal fluid neural cell adhesion molecule levels and their correlation with clinical variables in patients with schizophrenia, bipolar disorder, and major depressive disorder
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY,76:12-18 2017(Jun.)
Author:Shinsuke Hidese; Kotaro Hattori; Daimei Sasayama; Tomoko Miyakawa; Ryo Matsumura; Yuuki Yokota; Ikki Ishida; Junko Matsuo; Takamasa Noda; Sumiko Yoshida; Toshiya Teraishi; Hiroaki Hori; Miho Ota; Hiroshi Kunugi
Abstract:Purpose: Neural cell adhesion molecule (NCAM) plays an important role in neural plasticity, and its altered function has been implicated in psychiatric disorders. However, previous studies have yielded inconsistent results on cerebrospinal fluid (CSF) NCAM levels in psychiatric disorders. The aim of our study was to examine CSF NCAM levels in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD), and their possible relationship with clinical variables. Methods: The participants comprised 85 patients with schizophrenia, 57 patients with BD, 83 patients with MDD and 111 healthy controls, all matched for age, sex, and Japanese ethnicity. The CSF samples were drawn using a lumbar puncture and NCAM levels were quantified by an enzyme-linked immunosorbent assay. Results: Analysis of covariance controlling for age and sex revealed that CSF NCAM levels were lower in all patients (p = 0.033), and in those with BD (p = 0.039), than in the controls. NCAM levels positively correlated with age in patients with BD (p < 0.01), MDD (p < 0.01), and the controls (p < 0.01). NCAM levels negatively correlated with depressive symptom scores in patients with BD (p = 0.040). In patients with schizophrenia, NCAM levels correlated negatively with negative symptom scores (p = 0.029), and correlated positively with scores for cognitive functions such as category fluency (p = 0.011) and letter fluency (p = 0.023) scores. Conclusion: We showed that CSF NCAM levels were lower in psychiatric patients, particularly bipolar patients than in the controls. Furthermore, we found correlations of NCAM levels with clinical symptoms in patients with BD and in those with schizophrenia, suggesting the involvement of central NCAM in the symptom formation of severe psychiatric disorders. (C) 2017 Elsevier Inc. All rights reserved.


Negative Correlation between Serum Cytokine Levels and Cognitive Abilities in Children with Autism Spectrum Disorder
Journal of Intelligence,5(2):19 2017(May)
Author:Sasayama D, Kurahashi K, Oda K, Yasaki T, Yamada Y, Sugiyama N, Inaba Y, Harada Y, Washizuka S, Honda H.
Abstract:Journal of Intelligence


Genome-wide quantitative trait loci mapping of the human cerebrospinal fluid proteome
HUMAN MOLECULAR GENETICS,26(1):44-51 2017(Jan.)
Author:Daimei Sasayama; Kotaro Hattori; Shintaro Ogawa; Yuuki Yokota; Ryo Matsumura; Toshiya Teraishi; Hiroaki Hori; Miho Ota; Sumiko Yoshida; Hiroshi Kunugi
Abstract:Cerebrospinal fluid (CSF) is virtually the only one accessible source of proteins derived from the central nervous system (CNS) of living humans and possibly reflects the pathophysiology of a variety of neuropsychiatric diseases. However, little is known regarding the genetic basis of variation in protein levels of human CSF. We examined CSF levels of 1,126 proteins in 133 subjects and performed a genome-wide association analysis of 514,227 single nucleotide polymorphisms (SNPs) to detect protein quantitative trait loci (pQTLs). To be conservative, Spearman's correlation was used to identify an association between genotypes of SNPs and protein levels. A total of 421 cis and 25 trans SNP-protein pairs were significantly correlated at a false discovery rate (FDR) of less than 0.01 (nominal P<7.66 x 10(-9)). Cis-only analysis revealed additional 580 SNP-protein pairs with FDR<0.01 (nominal P<2.13 x 10(-5)). pQTL SNPs were more likely, compared to non-pQTL SNPs, to be a disease/trait-associated variants identified by previous genome-wide association studies. The present findings suggest that genetic variations play an important role in the regulation of protein expression in the CNS. The obtained database may serve as a valuable resource to understand the genetic bases for CNS protein expression pattern in humans.


A case of severe parkinsonism in an elderly person induced by valproic acid
PSYCHOGERIATRICS,17(1):76-77 2017(Jan.)
Author:Haruka Tada; Tomomi Ogihara; Toshinori Nakamura; Daimei Sasayama; Nobuhiro Sugiyama; Yuka Takahashi; Shinsuke Washizuka; Naoji Amano


Jitteriness/Anxiety Syndrome Developing Immediately following Initiation of Oral Administration of Sertraline.
Case Rep Psychiatry,2017:1319505 2017
Author:Nakamura T, Sugiyama N, Sasayama D, Hagiwara T, Washizuka S.
Abstract:Case Rep Psychiatry


Effective Treatment of Night Terrors and Sleepwalking with Ramelteon
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY,26(10):948-948 2016(Dec.)
Author:Daimei Sasayama; Shinsuke Washizuka; Hideo Honda


Patterns of hippocampal atrophy differ among Alzheimer's disease, amnestic mild cognitive impairment, and late-life depression
Psychogeriatrics,16(6):355-361 2016(Nov.)
Author:Taisuke Joko; Shinsuke Washizuka; Daimei Sasayama; Shin Inuzuka; Tomomi Ogihara; Takehiko Yasaki; Tetsuya Hagiwara; Nobuhiro Sugiyama; Tohru Takahashi; Tomoki Kaneko; Tokiji Hanihara; Naoji Amano
Abstract:AimThis study investigated whether the characteristic changes in hippocampal atrophy seen in coronal scans are useful for differentiating Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and major depressive disorder (MDD). MethodsSubjects included 58 patients with AD, 33 with aMCI, 20 with MDD, and 22 normal controls, all aged 60 years or older. For each subject, eight coronal short TI inversion recovery images perpendicular to the hippocampal longitudinal axis were obtained. Images were manually measured using the conventional region of interest method of quantitative analysis. ResultsThe overall trend in the corrected volumes of the hippocampus was AD < aMCI < MDD < normal controls. We found atrophy in all slices in AD, atrophy centred on the hippocampal head in aMCI, and atrophy in the slice of the hippocampal body 12 mm from the amygdala in MDD. ConclusionsThe present study suggested that our method of comparing hippocampal atrophy by region may be useful in distinguishing AD, aMCI, MDD, and normal controls.


Suvorexant induced restless legs syndrome; a case report
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,19:285-285 2016(Jun.)
Author:Tomomi Ogihara; Daimei Sasayama; Shinsuke Washizuka


Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,19:118-119 2016(Jun.)
Author:Shintaro Ogawa; Kotaro Hattori; Teruhiko Higuchi; Hiroaki Hori; Hiroshi Kunugi; Ryo Matsumura; Junko Matsuo; Nobutaka Motohashi; Takamasa Noda; Yoshiaki Ohashi; Miho Ota; Daimei Sasayama; Hajime Sato; Toshiya Teraishi; Yuki Yokota; Sumiko Yoshida


Parkinsonism induced by valproic acid: a case report and review of literature
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,19:66-66 2016(Jun.)
Author:Haruka Tada; Tomomi Ogihara; Daimei Sasayama; Toshinori Nakamura; Nobuhiro Sugiyama; Yuka Takahashi; Shinsuke Washizuka


Evaluation of plasma and cerebrospinal fluid G72 protein levels and their correlations with psychiatric symptoms in schizophrenia and major depression
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,19:244-245 2016(Jun.)
Author:Sayuri Ishiwata-Matsushima; Kotaro Hattori; Hiroshi Kunugi; Ryo Matsumura; Tomoko Miyakawa; Toru Nishikawa; Daimei Sasayama; Toshiya Teraishi; Yuuki Yokota


Association between peripheral cytokine levels and cognitive abilities in children with autism spectrum disorder
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,19:175-175 2016(Jun.)
Author:Daimei Sasayama; Hideo Honda; Yuji Inaba; Kana Kurahashi; Kayoko Oda; Shinsuke Washizuka


Altered balance between monoamine metabolites in human cerebrospinal fluid with major depressive disorder.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY,19:133-134 2016(Jun.)
Author:Hyung Shin Yoon; Kotaro Hattori; Hiroshi Kunugi; Shintaro Ogawa; Miho Ota; Daimei Sasayama; Toyisha Teraishi


Sex differences in the serum level of endogenous ligands for estrogen receptor beta in the elderly population
SCIENTIFIC REPORTS,6:- 2016(May)
Author:Miyuki Kobayashi; Nobuhiro Sugiyama; Daimei Sasayama; Hidehiko Sasamoto; Yoshimichi Miyashiro; Kunimasa Arima; Shinsuke Washizuka
Abstract:Animal studies suggest that estrogen receptor beta (ER beta)-agonists, but not ER alpha-agonists, are antidepressants. Several endogenous ligands for ER beta have been proposed, including 5 alpha-androstane-3 beta,17 beta-diol (3 beta Adiol), Androstenediol (Delta 5-diol), and 7 alpha-hydroxydehydroepiandrosterone (7 alpha-OH-DHEA). The aim of this study was to determine the serum and salivary levels of natural ER beta ligands in men and women with and without past depressive episodes in the elderly population. DHEA (a precursor of 3 beta Adiol, Delta 5-diol, and 7 alpha-OH-DHEA), 17 beta-estradiol (E2), and cortisol (F) were also measured. Samples were collected from 51 subjects and liquid chromatography tandem mass spectrometry was used for measurement. Comparisons were made between groups based on sex and depression history. E2, 3 beta Adiol, and Delta 5-diol levels were significantly lower in women than in men regardless of depression history. There were no significant differences between men and women in DHEA or 7 alpha-OH-DHEA levels. DHEA was significantly lower in women with depression than in women without depression. Reduced DHEA levels may be related to depression vulnerability in women. Further studies are needed to determine the mechanism underlying sex differences in the prevalence of depression and increased risk of depression during menopause. Not only E2 but also two other estrogenic steroids (3 beta Adiol and Delta 5-diol) should be involved in these studies.


Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses
SCIENTIFIC REPORTS,6:--199 2016(Jan.)
Author:Hiroaki Hori; Daimei Sasayama; Toshiya Teraishi; Noriko Yamamoto; Seiji Nakamura; Miho Ota; Kotaro Hattori; Yoshiharu Kim; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Several microarray-based studies have investigated gene expression profiles in major depressive disorder (MDD), yet with highly variable findings. We examined blood-based genome-wide expression signatures of MDD, focusing on molecular pathways and networks underlying differentially expressed genes (DEGs) and behaviours of hypothesis-driven, evidence-based candidate genes for depression. Agilent human whole-genome arrays were used to measure gene expression in 14 medication-free outpatients with MDD who were at least moderately ill and 14 healthy controls matched pairwise for age and sex. After filtering, we compared expression of entire probes between patients and controls and identified DEGs. The DEGs were evaluated by pathway and network analyses. For the candidate gene analysis, we utilized 169 previously prioritized genes and examined their case-control separation efficiency and correlational co-expression network in patients relative to controls. The 317 screened DEGs mapped to a significantly over-represented pathway, the "synaptic transmission" pathway. The protein-protein interaction network was also significantly enriched, in which a number of key molecules for depression were included. The co-expression network of candidate genes was markedly disrupted in patients. This study provided evidence for an altered molecular network along with several key molecules in MDD and confirmed that the candidate genes are worthwhile targets for depression research.


自閉スペクトラム症と児童精神科医療
信州医学雑誌,64(6):329-339 2016
Author:篠山 大明
Abstract:信州医学雑誌


Effect of electroconvulsive therapy on gray matter volume in major depressive disorder
JOURNAL OF AFFECTIVE DISORDERS,186:186-191 2015(Nov.)
Author:Miho Ota; Takamasa Noda; Noriko Sato; Mitsutoshi Okazaki; Masatoshi Ishikawa; Kotaro Hattori; Hiroaki Hori; Daimei Sasayama; Toshiya Teraishi; Daichi Sone; Hiroshi kunugi
Abstract:Background: Although the clinical efficacy of electroconvulsive therapy (ECT) is well established, the underlying mechanisms of action remain elusive. The aim of this study was to elucidate structural changes of the brain following ECT in patients with major depressive disorder (MDD).Method: Fifteen patients with MDD underwent magnetic resonance imaging scanning before and after ECT. Their gray matter volumes were compared between pre- and post-ECT. Results: There were significant volume increases after ECU in the bilateral medial temporal cortices, inferior temporal cortices, and right anterior cingulate. Further, the increase ratio was correlated with the clinical improvement measured by the Hamilton Depression Rating scale. Limitation: All subjects were treated with antidepressants that could have a neurotoxic or neuroprotective effect on the brain. Conclusions: We found that there were significant increases of gray matter volume in medial temporal lobes following ECU, suggesting that a neurotrophic effect of ECT could play a role in its therapeutic effect. (C) 2015 Elsevier B.V. All rights reserved.


C-13-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder
SCIENTIFIC REPORTS,5:- 2015(Nov.)
Author:Toshiya Teraishi; Hiroaki Hori; Daimei Sasayama; Junko Matsuo; Shintaro Ogawa; Miho Ota; Kotaro Hattori; Masahiro Kajiwara; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Altered tryptophan-kynurenine (KYN) metabolism has been implicated in major depressive disorder (MDD). The L-[1-C-13] tryptophan breath test (C-13-TBT) is a noninvasive, stable-isotope tracer method in which exhaled (CO2)-C-13 is attributable to tryptophan catabolism via the KYN pathway. We included 18 patients with MDD (DSM-IV) and 24 age-and sex-matched controls. C-13-tryptophan (150 mg) was orally administered and the (CO2)-C-13/ (CO2)-C-12 ratio in the breath was monitored for 180 min. The cumulative recovery rate during the 180-min test (CRR0-180; %), area under the Delta(CO2)-C-13-time curve (AUC; %* min), and the maximal Delta(CO2)-C-13 (C-max; %) were significantly higher in patients with MDD than in the controls (p = 0.004, p = 0.008, and p = 0.002, respectively). Plasma tryptophan concentrations correlated negatively with Cmax in both the patients and controls (p = 0.020 and p = 0.034, respectively). Our results suggest that the C-13-TBT could be a novel biomarker for detecting a subgroup of MDD with increased tryptophan-KYN metabolism.


精神医学のフロンティア 健常者の感覚運動フィルター機構に対するL-テアニンの影響
精神神経学雑誌,117(10):813-819 2015(Oct.)
Author:太田 深秀; 若林 千里; 松尾 淳子; 木下 裕紀子; 堀 弘明; 服部 功太郎; 篠山 大明; 寺石 俊也; 大部 聡子; 小澤 隼人; 大久保 勉; 功刀 浩
Abstract:L-テアニンは日本で1950年に玉露から発見されたアミノ酸の一種である.これまでの研究からL-テアニンは認知機能に影響を及ぼすことが明らかになっている.これまでに我々のグループは,感覚運動フィルター機構の指標の1つであるプレパルス抑制試験(PPI)をMK-801により障害したマウスにL-テアニンを投与するとPPIが改善することを明らかにした.今回我々は健常被験者を対象にL-テアニンがもつPPIへの影響を検討した.14名の被験者(男性7名,女性7名,平均年齢31.0±7.0歳)を対象に,各被験者にL-テアニンを0,200,400,もしくは600mgの計4回,単回摂取をしていただき,内服後90分のPPIを測定した.被験者には摂取量がわからないように行った.その結果,200mg,400mgを摂取した際には,プラセボのみを摂取したときと比較してPPI抑制率に改善がみられた.しかし600mgを摂取したときには有意な改善は認められなかった.他にstartleに対する反応性や,繰り返し検査による習慣性はL-テアニン摂取量と有意な関連は認められなかった.このことからL-テアニンはある一定の濃度範囲においてPPIを改善する効果を示すことが明らかとなった.(著者抄録)


A case-control study of the difficulties in daily functioning experienced by children with depressive disorder
JOURNAL OF AFFECTIVE DISORDERS,179:167-174 2015(Jul.)
Author:Masahide Usami; Yoshitaka Iwadare; Kyota Watanabe; Hirokage Ushijima; Masaki Kodaira; Takashi Okada; Daimei Sasayama; Nobuhiro Sugiyama; Kazuhiko Saito
Abstract:Objective: The parent-assessed children-with-difficulties questionnaire (Questionnaire-Children with Difficulties; QCD) is designed to evaluate a child's difficulties in functioning during specific periods of the day. This study aimed to use the QCD to evaluate the difficulties in daily functioning experienced by children with depressive disorders. Methods: A case-control design was used. The cases comprised 90 junior high school students with depressive disorder, whereas a community sample of 363 junior high school students was enrolled as controls. Behaviors were assessed using the QCD, Depression Self-Rating Scale (DSRS), Tokyo Autistic Behavior Scale (TABS), attention deficit hyperactivity disorder-rating scale (ADHD-RS), and Oppositional Defiant Behavior Inventory (ODBI). We then analyzed the effects of sex and diagnosis on the QCD scores as well as the correlation coefficients between the QCD and the other questionnaires. Results: We included 90 cases (33 boys, 57 girls) with depressive disorders and 363 controls (180 boys, 183 girls). The QCD scores for the children with depressive disorders were significantly lower compared with those from the community sample (P< 0.001). The morning, school-time, and night subscores of the QCD were lower for the children with both depressive disorders and truancy problems than for those with depressive disorders alone (P< 0.001). Significant correlations were observed between the following: the night QCD subscore and the DSRS scores among boys, the morning QCD subscore and ADHD-RS inattention scores for all groups, and the evening QCD subscore and the TABS score. Conclusions: Parents reported that children with depressive disorders experienced greater difficulties in completing basic daily activities compared with community controls. These difficulties were dependent on sex, symptoms, and the time of day. The use of QCD to assess children with depressive disorders enables clinicians to clarify the Lime periods at which the children face difficulties. (C) 2015 Elsevier By. All rights reserved.


White matter abnormalities in major depressive disorder with melancholic and atypical features: A diffusion tensor imaging study
PSYCHIATRY AND CLINICAL NEUROSCIENCES,69(6):360-368 2015(Jun.)
Author:Miho Ota; Takamasa Noda; Noriko Sato; Kotaro Hattori; Hiroaki Hori; Daimei Sasayama; Toshiya Teraishi; Anna Nagashima; Satoko Obu; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:AimThe DSM-IV recognizes some subtypes of major depressive disorder (MDD). It is known that the effectiveness of antidepressants differs among the MDD subtypes, and thus the differentiation of the subtypes is important. However, little is known as to structural brain changes in MDD with atypical features (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us to examine possible differences in white matter integrity assessed with diffusion tensor imaging (DTI) between these two subtypes. MethodsSubjects were 21 patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared fractional anisotropy and mean diffusivity value derived from DTI data on a voxel-by-voxel basis among the two diagnostic groups and healthy subjects. ResultsThere were significant decreases of fractional anisotropy and increases of mean diffusivity in patients with MDD compared with healthy subjects in the corpus callosum, inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. However, we detected no significant difference in any brain region between mMDD and aMDD. ConclusionOur results suggest that patients with MDD had reduced white matter integrity in some regions; however, there was no major difference between aMDD and mMDD.


Increased protein and mRNA expression of resistin after dexamethasone administration.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme,47(6):433-438 2015(Jun.)
Author:Sasayama D; Hori H; Nakamura S; Yamamoto N; Hattori K; Teraishi T; Ota M; Kunugi H


Increased cerebrospinal fluid fibrinogen in major depressive disorder
SCIENTIFIC REPORTS,5:- 2015(Jun.)
Author:Kotaro Hattori; Miho Ota; Daimei Sasayama; Sumiko Yoshida; Ryo Matsumura; Tomoko Miyakawa; Yuuki Yokota; Shinobu Yamaguchi; Takamasa Noda; Toshiya Teraishi; Hiroaki Hori; Teruhiko Higuchi; Shinichi Kohsaka; Yu-ichi Goto; Hiroshi Kunugi
Abstract:Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9-39.1, p = 0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.


Concerns Expressed by Parents of Children with Pervasive Developmental Disorders for Different Time Periods of the Day: A Case-Control Study
PLOS ONE,10(4):- 2015(Apr.)
Author:Yoshinori Sasaki; Masahide Usami; Daimei Sasayama; Takashi Okada; Yoshitaka Iwadare; Kyota Watanabe; Hirokage Ushijima; Tetsuya Tanaka; Maiko Harada; Hiromi Tanaka; Masaki Kodaira; Nobuhiro Sugiyama; Tetsuji Sawa; Kazuhiko Saito
Abstract:Background/Aim The Questionnaire: Children with Difficulties (QCD) is a parent-assessed questionnaire designed to evaluate child's difficulties in functioning during specific periods of the day. This study aimed to evaluate difficulties in daily functioning of children and adolescents with pervasive developmental disorder (PDD) using the QCD. Results were compared with those for a community sample. Methods A case-control design was used. The cases comprised elementary school students (182 males, 51 females) and junior high school students (100 males, 39 females) with PDD, whereas a community sample of elementary school students (568 males, 579 females) and junior high school students (180 males, 183 females) was enrolled as controls. Their behavior was assessed using the QCD, the Tokyo Autistic Behavior Scale (TABS), the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI) for elementary and junior high school students, respectively. Effects of gender and diagnosis on the QCD scores were analyzed. Correlation coefficients between QCD and TABS, ADHD-RS, and ODBI scores were analyzed. Results The QCD scores for the children with PDD were significantly lower compared with those from the community sample (P < 0.001). Significantly strong correlations were observed in more areas of the ADHD-RS and ODBI scores compared with the TABS scores. Conclusions Children with PDD experienced greater difficulties in completing basic daily activities; moreover, their QCD scores revealed stronger associations with their ADHD-RS and ODBI scores in comparison with their TABS scores. The difficulties of PDD, ADHD and OBDI symptoms combined in children makes it necessary to assess all diagnoses before any therapy for PDD is initiated in order to be able to evaluate its results properly.


Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder
SCIENTIFIC REPORTS,5:- 2015(Jan.)
Author:Shintaro Ogawa; Kotaro Hattori; Daimei Sasayama; Yuki Yokota; Ryo Matsumura; Junko Matsuo; Miho Ota; Hiroaki Hori; Toshiya Teraishi; Sumiko Yoshida; Takamasa Noda; Yoshiaki Ohashi; Hajime Sato; Teruhiko Higuchi; Nobutaka Motohashi; Hiroshi Kunugi
Abstract:Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients withMDD(42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the depressed patients and controls. After Bonferroni correction, only ethanolamine (EA) levels remained significantly reduced in depressed patients (nominal P = 0.0000011). A substantial proportion of the depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1 mu M) (P = 0.000033; OR = 11.6, 95% CI: 3.1-43.2). When patients with low EA and those with high EA levels were compared, the former had higher scores for overall depression severity (P = 0.0033) and 'Somatic Anxiety' symptoms (P = 0.00026). In unmedicated subjects, CSF EA levels showed a significant positive correlation with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P = 0.019). To our knowledge, this is the first study showing that patients with MDD have significantly lower CSF EA concentrations compared with control subjects. CSF EA could be a state-dependent biomarker for a subtype of MDD.


Personality in remitted major depressive disorder with single and recurrent episodes assessed with the Temperament and Character Inventory
PSYCHIATRY AND CLINICAL NEUROSCIENCES,69(1):3-11 2015(Jan.)
Author:Toshiya Teraishi; Hiroaki Hori; Daimei Sasayama; Junko Matsuo; Shintaro Ogawa; Ikki Ishida; Anna Nagashima; Yukiko Kinoshita; Miho Ota; Kotaro Hattori; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:AimPrevious studies consistently reported increased harm avoidance (HA) assessed with the Temperament and Character Inventory (TCI) in patients with major depressive disorder (MDD). However, such findings may have been related with depression severity and number of depressive episodes. The aims of the present study were twofold: to examine TCI personality profile in remitted MDD (DSM-IV) patients and to compare TCI personality between MDD patients with single episode (SGL-MDD) and those with recurrent episodes (REC-MDD) in order to elucidate personality profile associated with recurrence. MethodsTCI was administered to 86 outpatients with remitted SGL-MDD (12 male and 17 female patients; mean age 43.212.1 years) and REC-MDD (26 male and 31 female patients; 40.311.6 years), and 529 healthy controls (225 men and 304 women; 43.4 +/- 15.5 years), matched for age, sex and education years. Logistic regression analyses were performed in which single/recurrent episodes of depression were the dependent variable and age, sex, age of onset, family history of psychiatric disease and TCI scores were entered as possible predictors. ResultsThe remitted MDD patients had significantly higher scores on HA (P<0.001) and lower scores on self-directedness (P<0.001), compared with the controls. HA (P=0.03), its subscore, fatigability (P=0.03), and family history of psychiatric disease were found to be positive predictors for recurrence. ConclusionThere are differences in personality profile between remitted MDD patients and controls, and between remitted REC-MDD and SGL-MDD patients, suggesting that they are trait markers. HA and fatigability might be useful to assess risk for recurrence of depression.


Association between the common functional FKBP5 variant (rs1360780) and brain structure in a non-clinical population
JOURNAL OF PSYCHIATRIC RESEARCH,58:96-101 2014(Nov.)
Author:Takashi Fujii; Miho Ota; Hiroaki Hori; Kotaro Hattori; Toshiya Teraishi; Daimei Sasayama; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:FK506 binding protein 5 (FKBP5) is induced by stress and regulates glucocorticoid receptor sensitivity. The T allele of the single nucleotide polymorphism (SNP) FKBP5 rs1360780 (C/T) is associated with an increased risk of post-traumatic stress disorder (PTSD) and reduced hippocampal volume in traumatized or depressed subjects. To examine whether this SNP affects brain structures that regulate stress response, we obtained magnetic resonance imaging data of the brain in 162 healthy subjects using a 1.5 T system. Gray matter volumes and diffusion tensor imaging data were compared between individuals with and without the T allele, using optimized voxel-based morphometry. We found that the dorsal anterior cingulate cortex (dACC) volume was smaller in T carriers than in non-T carriers (P < 0.001). T carriers also showed significantly higher mean diffusivity values in the dACC and posterior cingulate cortex (PCC) compared with non-T carriers (P < 0.001). Our results suggest that carrying the T allele of FKBP5 rs1360780 is associated with smaller gray matter volumes in the dACC and altered white matter integrity in the dACC and PCC in the non-clinical population, which might constitute the structural basis of stress-related psychiatric disorders including PTSD. (C) 2014 Elsevier Ltd. All rights reserved.


子どもの日常生活チェックリストの開発と児童精神科臨床
日本児童青年精神医学会総会抄録集,55回:9-9 2014(Oct.)
Author:宇佐美 政英; 篠山 大明; 杉山 暢宏; 細金 奈奈; 金 樹英; 山下 裕史郎; 小平 雅基; 渡部 京太; 岩垂 喜貴; 沢 哲司; 齊藤 万比古


Relationship between Lifetime Suicide Attempts and Schizotypal Traits in Patients with Schizophrenia
PLOS ONE,9(9):- 2014(Sep.)
Author:Toshiya Teraishi; Hiroaki Hori; Daimei Sasayama; Junko Matsuo; Shintaro Ogawa; Ikki Ishida; Anna Nagashima; Yukiko Kinoshita; Miho Ota; Kotaro Hattori; Hiroshi Kunugi
Abstract:Patients with schizophrenia are at increased risk for suicide. Various risk factors for suicide have been reported in schizophrenia; however, few studies have examined the association between personality traits and suicidal behavior. We administered the Schizotypal Personality Questionnaire (SPQ) to 87 Japanese patients with schizophrenia (49 males; mean age 38.1 +/- 10.6 years) with and without a history of suicide attempts (SA and nSA groups, respectively), and 322 controls (158 males; mean age 40.8 +/- 13.9 years). As expected, an analysis of covariance (ANCOVA) controlling for age and sex showed that all SPQ indices (total SPQ score and all three factors, i.e., cognitive-perceptual, interpersonal, and disorganized) were significantly higher in patients with schizophrenia (SA+nSA groups), than controls (p<0.001 for all comparisons). Furthermore, there were significant differences in the total score and the interpersonal and disorganized factors between the SA and nSA groups (nSA<SA, p<0.01 for all comparisons). Receiver operating characteristic analysis showed that a total SPQ score of 33.5 was the optimal cut-off value to discriminate the SA group from the nSA group (chi(2)[1] = 10.6, p = 0.002, odds ratio: 4.7, 95% confidence interval: 1.8-12.1, sensitivity: 0.70, specificity: 0.67). These results suggest that high schizotypy is associated with lifetime suicide attempts, and that the total SPQ score might be useful to assess the risk of suicide attempt in patients with schizophrenia.


Effect of L-theanine on sensorimotor gating in healthy human subjects
PSYCHIATRY AND CLINICAL NEUROSCIENCES,68(5):337-343 2014(May)
Author:Miho Ota; Chisato Wakabayashi; Junko Matsuo; Yukiko Kinoshita; Hiroaki Hori; Kotaro Hattori; Daimei Sasayama; Toshiya Teraishi; Satoko Obu; Hayato Ozawa; Hiroshi Kunugi
Abstract:Aim l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea. Growing evidence has suggested the possible effects of l-theanine on cognition. Previously, we found that l-theanine attenuates MK-801-induced deficit in prepulse inhibition (PPI) in mice. In this study, we examined the effect of l-theanine in increasing the PPI in healthy humans. Methods The subjects were 14 healthy adults who underwent PPI testing as a measure of sensorimotor gating 90min after an oral intake of l-theanine (0, 200, 400, or 600mg). PPI tests were done by examiners who were blind to the dose. Results The administration of 200mg of l-theanine and that of 400mg, but not 600mg, significantly increased the % PPI compared to the baseline (0mg). There was no significant relation between the dose of l-theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of l-theanine correlated with the dose of l-theanine. Conclusion The observed effect with 200-400mg of l-theanine on PPI suggested that l-theanine at a particular dose range increases sensorimotor gating in humans.


POSSIBLE ASSOCIATION BETWEEN ITIH3 GENE POLYMORPHISM AND SCHIZOPHRENIA IN A JAPANESE POPULATION
SCHIZOPHRENIA RESEARCH,153:S362-S362 2014(Apr.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Masahiko Tatsumi; Kotaro Hattori; Miho Ota; Teruhiko Higuchi; Hiroshi Kunugi


Effect of the common functional FKBP5 variant (rs1360780) on the hypothalamic-pituitary-adrenal axis and peripheral blood gene expression
PSYCHONEUROENDOCRINOLOGY,42:89-97 2014(Apr.)
Author:Takashi Fujii; Hiroaki Hori; Miho Ota; Kotaro Hattori; Toshiya Teraishi; Daimei Sasayama; Noriko Yamamoto; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Regulation of hypothalamic-pituitary-adrenal (HPA) axis reactivity plays an important role in the development of stress-related psychiatric disorders. FK506 binding protein 5 (FKBP5) modulates HPA axis reactivity via glucocorticoid receptor (GR; NR3C1) sensitivity and signaling. The T allele of the single nucleotide polymorphism, FKBP5 rs1360780 (C/T), is associated with higher FKBP5 induction by glucocorticoids. In the present study, we performed the dexamethasone/corticotropin releasing hormone (DEX/CRH) test and quantitative real-time PCR analysis of peripheral blood mononuclear cell (PBMC) cDNA samples in 174 and 278 non-clinical individuals, respectively. We found increased suppression of the stress hormone (cortisol) response to the DEX/CRH test (P = 0.0016) in aged (>50 years) individuals carrying the Tallele compared with aged non-T allele carriers. Tcarriers showed significant age-related changes in GR and FKBP5 mRNA expression levels in PBMCs (P = 0.0013 and P = 0.00048, respectively). Our results indicate that FKBP5 rs1360780 regulates HPA axis reactivity and expression levels of GR and FKBP5 in PBMCs in an age-dependent manner. Because these phenotypes of aged Tcarriers are similar to endophenotypes of people with post-traumatic stress disorder, our findings may be useful for determining the molecular mechanisms, treatment, and preventive strategies for this disease. (C) 2014 Elsevier Ltd. All rights reserved.


Cognitive effects of the ANK3 risk variants in patients with bipolar disorder and healthy individuals
JOURNAL OF AFFECTIVE DISORDERS,158:90-96 2014(Apr.)
Author:Hiroaki Hori; Noriko Yamamoto; Toshiya Teraishi; Miho Ota; Takashi Fujii; Daimei Sasayama; Junko Matsuo; Yukiko Kinoshita; Kotaro Hattori; Anna Nagashima; Ikki Ishida; Norie Koga; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Background: Genetic variants within the ankyrin 3 gene (ANK3) have been identified as a risk factor for bipolar disorder. ANK3 influences action potential generation by clustering sodium gated channels and plays an integral role in neurotransmission. Thus, this gene may influence cognition, a process compromised in bipolar disorder. We investigated whether genetic variants of ANK3 would be associated with an array of cognitive functions in patients with bipolar disorder and healthy individuals. Methods: In a sample of 49 patients with bipolar disorder and 633 healthy subjects, we examined possible effects of 2 risk variants within ANK3, rs10994336 and rs10761482, on 7 neurocognitive domains. Results: Compared to healthy subjects, patients with bipolar disorder demonstrated significantly poorer performance on most of the cognitive domains examined. The risk C-allele of rs10761482 was significantly associated with worse performance on verbal comprehension, logical memory and processing speed in patients. This allele was significantly associated with worse performance on executive function and visual memory in healthy individuals. No significant association was observed between rs10994336 and cognition either in patients or healthy individuals. Limitations: The sample size of patients with bipolar disorder was small, and most of the patients wcrc on psychotropic medication. Conclusions: These results indicate that a risk variant within ANK3 may have an impact on neurocognitive function, suggesting a mechanism by which ANK3 confers risk for bipolar disorder. (C) 2014 Elsevier B.V. All rights reserved


CEREBROSPINAL FLUID BIOMARKERS FOR SCHIZOPHRENIA REVEALED BY A CICAT PROTEOMIC ANALYSES
SCHIZOPHRENIA RESEARCH,153:S98-S99 2014(Apr.)
Author:Hattori, Kotaro; Goto, Yuichi; Yoshida, Sumiko; Sasayama, Daimei; Komurasaki, Toshi; Chaki, Shigeyuki; Fujii, Yasuyuki; Yoshimizu, Takao; Kunugi, Hiroshi
Abstract:SCHIZOPHRENIA RESEARCH


ITIH3 polymorphism may confer susceptibility to psychiatric disorders by altering the expression levels of GLT8D1
JOURNAL OF PSYCHIATRIC RESEARCH,50:79-83 2014(Mar.)
Author:Daimei Sasayama; Hiroaki Hori; Noriko Yamamoto; Seiji Nakamura; Toshiya Teraishi; Masahiko Tatsumi; Kotaro Hattori; Miho Ota; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations. The aim of the study was to replicate the association of rs2535629 with schizophrenia and major depressive disorder (MDD) in Japanese subjects. A total of 611 patients with schizophrenia, 868 with MOD, and 1193 healthy controls were successfully genotyped for rs2535629. A significant difference in allele distribution was found between patients with schizophrenia and controls (odds ratio [OR] = 1.21, 95% confidence interval [Cl]: 1.05-1.39, P = 0.0077). A similar trend was found for patients with MDD (OR = 1.11,95% CI: 0.98-1.26, P = 0.092). The allele distribution in the combined patient group (schizophrenia and MDD) was significantly different from that of the control group (OR = 1.15, 95% CI: 1.03-1.28, P = 0.011). Gene expression microarray analysis of whole blood samples in 39 MDD patients and 40 healthy controls showed that rs2535629 has a strong influence on the expression levels of ITIH4 and GLT8D1. The expression levels of GLT8D1 were significantly higher in patients with MDD than in controls (P = 0.021). To our knowledge, the present study showed for the first time the association of rs2535629 with psychiatric disorders in an Asian population. Our findings suggest that rs2535629 influences the susceptibility to psychiatric disorders by affecting the expression level of GLT8D1. (C) 2013 Elsevier Ltd. All rights reserved.


Comparison of alterations in cerebral hemoglobin oxygenation in late life depression and Alzheimer's disease as assessed by near-infrared spectroscopy
BEHAVIORAL AND BRAIN FUNCTIONS,10:- 2014(Mar.)
Author:Hisashi Kito; Akiko Ryokawa; Yoshihiro Kinoshita; Daimei Sasayama; Nobuhiro Sugiyama; Tomomi Ogihara; Takehiko Yasaki; Tetsuya Hagiwara; Shin Inuzuka; Tohru Takahashi; Hirokazu Genno; Hiroshi Nose; Tokiji Hanihara; Shinsuke Washizuka; Naoji Amano
Abstract:Background: Patients with Alzheimer's disease (AD) often present with apathy symptoms resembling the decreased motivation observed in depressed patients. Therefore, differentiating the initial phase of AD from late life depression may be difficult in some cases. Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that uses near-infrared light to measure changes in hemoglobin concentration on the cortical surface during activation tasks. The objective of this study was to investigate differences in brain activation associated with late life depression and with AD by means of NIRS. Methods: NIRS was performed in 30 patients with depression, 28 patients with AD, and 33 healthy controls, all aged 60 years or older. During two tasks, a verbal fluency task and a visuospatial task, changes in oxygenated hemoglobin concentration in the frontal and parietal cortices were investigated. Results: In the visuospatial task, cortical activation was lower in the depressed group than in the AD group, and significant differences were observed in the parietal cortex. Conclusions: NIRS can detect differences in brain activation between patients with late life depression and those with AD. NIRS is a promising tool for the differential diagnosis of late life depression and AD.


Benzodiazepines, benzodiazepine-like drugs, and typical antipsychotics impair manual dexterity in patients with schizophrenia
JOURNAL OF PSYCHIATRIC RESEARCH,49:37-42 2014(Feb.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Junko Matsuo; Yukiko Kinoshita; Mitsutoshi Okazaki; Kunimasa Arima; Naoji Amano; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia. (C) 2013 Elsevier Ltd. All rights reserved.


A latent profile analysis of schizotypy, temperament and character in a nonclinical population: Association with neurocognition
JOURNAL OF PSYCHIATRIC RESEARCH,48(1):56-64 2014(Jan.)
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Junko Matsuo; Yukiko Kinoshita; Miho Ota; Kotaro Hattori; Hiroshi Kunugi
Abstract:Schizotypy is conceptualized as a latent personality construct that confers liability for schizophrenia, while it is also suggested that schizotypy can relate to certain favorable aspects. Investigating individual-level interactions between schizotypy and broader personality characteristics might give a clue to this question. We aimed to identify homogeneous classes of individuals based on schizotypy, temperament and character and to validate this classification using comprehensive neurocognitive data. We studied 455 nonclinical adults using the Schizotypal Personality Questionnaire, the Temperament and Character Inventory, and an array of neuropsychological tests. A latent profile analysis (LPA) of schizotypy, temperament and character was conducted, and cognitive performance was compared as a function of latent class membership. LPA provided a 3-class solution. Of the sample, 15% was classified into a "highpositive-schizotypy/adaptive" group characterized by high cognitive-perceptual but low interpersonal schizotypy, together with low harm avoidance and high self-directedness, cooperativeness and selftranscendence; 18% was classified into a "high-schizotypy/maladaptive" group characterized by overall high schizotypy, together with high harm avoidance and low self-directedness and cooperativeness; and 67% was classified into a "low-schizotypy/adaptive" group characterized by overall low schizotypy, together with intermediate-to-low harm avoidance, high self-directedness and intermediate-to-high cooperativeness. Overall cognitive performance of the high-positive-schizotypy/adaptive group was comparable to that of the low-schizotypy/adaptive group and superior to that of the high-schizotypy/maladaptive group. The present LPA clearly defines a group of individuals who have adaptive personality traits and intact neuropsychological functions despite high positive schizotypy, suggesting that there may be complex, nonlinear relationships between schizotypal traits and psychopathology. (C) 2013 Elsevier Ltd. All rights reserved.


Hypothalamic-pituitary-adrenal axis hyperactivity and brain differences in healthy women
Neuropsychobiology,68(4):205-211 2013(Dec.)
Author:Miho Ota; Hiroaki Hori; Noriko Sato; Daimei Sasayama; Kotaro Hattori; Toshiya Teraishi; Satoko Obu; Yasuhiro Nakata; Hiroshi Kunugi
Abstract:Background: Previous studies have suggested that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis leads to brain changes. However, few studies have examined the whole brain configuration for an association with HPA axis activity. We examined the relationship between HPA axis activity and the whole brain configuration. Methods: The subjects in this study were 34 healthy female volunteers. HPA axis activity was assessed by the dexamethasone/ corticotropin-releasing hormone test. Structural volumes of the brain and diffusion tensor images were obtained, and correlations were evaluated voxel-wise. Results: There was a significantly negative correlation between fractional anisotropy value and cortisol levels at 16:00 h (CL-2) in the anterior cingulum, left parahippocampus and right occipital region. There were significantly positive correlations between mean diffusivity value and CL-2 in the left hippocampus and bilateral parahippocampal regions. Conclusions: Our data suggest that reduced feedback of the HPA axis is associated with reduced neural connectivity throughout the brain, and such an association may be strong in the anterior cingulate, the hippocampus and the parahippocampal regions. © 2013 S. Karger AG, Basel.


What time periods of the day are concerning for parents of children with attention deficit hyperactivity disorder?
PLoS ONE,8(11):- 2013(Nov. 05)
Author:Masahide Usami; Takashi Okada; Daimei Sasayama; Yoshitaka Iwadare; Kyota Watanabe; Hirokage Ushijima; Masaki Kodaira; Nobuhiro Sugiyama; Tetsuji Sawa; Kazuhiko Saito
Abstract:Background/Aim: The questionnaire-children with difficulties (QCD) is a parent-assessed questionnaire designed to evaluate a child's difficulties in functioning during specific time periods of the day. In this study, the QCD was applied to determine the time periods of the day that are concerning for the parents of children with attention deficit hyperactivity disorder (ADHD). The results were compared with those for a community sample. Methods: Elementary and junior high school students with ADHD (243 boys, 55 girls) and a community sample of children (518 boys, 618 girls) were enrolled in this study. Their behaviors were assessed by the QCD, the ADHD-rating scale (ADHD-RS), and the Oppositional Defiant Behavior Inventory (ODBI). The effects of gender (boy/girl) and diagnosis (ADHD/community sample) on the total QCD score were analyzed across each school grade (elementary/junior high school). Correlation coefficients between QCD and ADHD-RS/ODBI scores were analyzed. Results: The QCD score for the ADHD group was significantly lower than that for the community sample (P < 0.001). There were significantly strong correlations between "evening" and ADHD-RS and ODBI scores for all children with ADHD (r > 0.41, P < 0.001) and between "night" and inattention and oppositional symptoms for the girls with ADHD (r > 0.40, P < 0.001). Conclusions: Parents reported that children with ADHD faced greater difficulties in completing basic daily activities compared with the community controls, particularly in the evening. Furthermore, these difficulties were related to the severity of ADHD symptoms. The parents' perceptions depended on the gender, ADHD and oppositional symptoms, and the time period of the day. This study determined that children with ADHD face greater difficulties in daily functioning compared with community sample children, that these difficulties are time-dependent, and that these difficulties were particularly experienced in the evening. © 2013 Usami et al.


Moderating effect of schizotypy on the relationship between smoking and neurocognition
European Psychiatry,28(8):457-462 2013(Oct.)
Author:H. Hori; J. Matsuo; T. Teraishi; D. Sasayama; Y. Kawamoto; Y. Kinoshita; M. Ota; K. Hattori; H. Kunugi
Abstract:Purpose: Smoking rates in schizotypic individuals are shown to be elevated, as in patients with schizophrenia, although findings on the association of smoking with different symptomatology of schizotypy have been mixed. Moreover, possible moderating effects of schizotypy on the relationship between smoking and cognition have not been well documented. Subjects and methods: The Schizotypal Personality Questionnaire (SPQ) and the full version of the Wechsler Memory Scale-Revised (WMS-R) were administered to 501 healthy adults. Subjects were divided into smokers (n=85) and non-smokers (n=416) based on the presence/absence of current smoking. Results: The analysis of covariance (ANCOVA) on the three factor scores as well as the total score of the SPQ, controlling for age and gender, revealed that cognitive-perceptual factor was significantly associated with an increased rate of smoking (P=0.048). The ANCOVA on the WMS-R indices, with smoking group as a fixed factor and age, gender and total SPQ score as covariates, revealed that the schizotypy-by-smoking interaction was significant for attention/working memory (P=0.029). Discussion and conclusion: Positive schizotypy may be associated with more smoking. Schizotypy and smoking could interact with each other to negatively affect attention/working memory. © 2012 Elsevier Masson SAS.


Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and adolescents with high-functioning pervasive developmental disorders
ANNALS OF GENERAL PSYCHIATRY,12:- 2013(Oct.)
Author:Tetsuji Sawa; Masaki Kodaira; Arata Oiji; Daimei Sasayama; Yoshitaka Iwadare; Hirokage Ushijima; Masahide Usami; Kyota Watanabe; Kazuhiko Saito
Abstract:Background: Several lines of evidence suggest that dysfunction of the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) contributes to the pathophysiology of pervasive developmental disorders (PDD). The purpose of this study was to investigate neuropsychological dysfunctions in both the DLPFC and OFC of children and adolescents with high-functioning PDD. Methods: The Iowa gambling task (IGT), which reflects OFC function, and the Wisconsin Card Sorting Test (WCST), which reflects DLPFC function, were assigned to 19 children and early adolescents with high-functioning PDD and 19 healthy controls matched for gender, age, and intelligence. Results: Compared to healthy controls, patients with high-functioning PDD displayed poorer performance on the IGT and the WCST. Conclusions: These results indicate that both the DLPFC and OFC could be impaired in children and early adolescents with high-functioning PDD.


Possible association of CUX1 gene polymorphisms with antidepressant response in major depressive disorder
PHARMACOGENOMICS JOURNAL,13(4):354-358 2013(Aug.)
Author:D. Sasayama; A. Hiraishi; M. Tatsumi; K. Kamijima; M. Ikeda; W. Umene-Nakano; R. Yoshimura; J. Nakamura; N. Iwata; H. Kunugi
Abstract:Association between response to antidepressant treatment and genetic polymorphisms was examined in two independent Japanese samples of patients with major depressive disorder (MDD). Genome-wide approach using the Illumina Human CNV370-quad Bead Chip was utilized in the analysis of the 92 MDD patients in the first sample. In all, 11 non-intergenic single-nucleotide polymorphisms with uncorrected allelic P-value <0.0001 were selected for the subsequent association analyses in the second sample of 136 MDD patients. Difference in allele distribution between responders and nonresponders were found in the second-stage sample for rs365836 and rs201522 of the CUX1 gene (P=0.005 and 0.004, respectively). The allelic P-values for rs365836 and rs201522 in both samples combined were 0.0000023 and 0.0000040, respectively. Our results provide the first evidence that polymorphisms of the CUX1 gene may be associated with response to antidepressant treatment in Japanese patients with MDD.


Possible association between common variants of the phenylalanine hydroxylase (PAH) gene and memory performance in healthy adults
BEHAVIORAL AND BRAIN FUNCTIONS,9:- 2013(Jul.)
Author:Toshiya Teraishi; Daimei Sasayama; Hiroaki Hori; Noriko Yamamoto; Takashi Fujii; Junko Matsuo; Anna Nagashima; Yukiko Kinoshita; Kotaro Hattori; Miho Ota; Sayaka Fujii; Hiroshi Kunugi
Abstract:Background: Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Rare mutations in PAH are causal to phenylketonuria (PKU), an autosomal recessive disease characterized by neuropsychiatric symptoms including intellectual disability. We examined whether there is an association between common single nucleotide polymorphisms (SNPs) of PAH and memory performance in the Japanese population. Methods: Subjects were 599 healthy adults (166 males and 433 females; mean age 43.8 +/- 15.5 years). The Wechsler Memory Scale-Revised (WMS-R) was administered to all participants to assess memory performance. Genotyping was performed for 6 selected tagging SNPs of PAH (rs1722387, rs3817446, rs1718301, rs2037639, rs10860936 and rs11111419). Results: Analyses of covariance controlling for sex and education years, indicated a significant association between a SNP (rs2037639) and age-corrected verbal memory index of WMS-R (nominal p = 0.0013) which remained significant after correction for multiple testing (p = 0.0013 < 0.0017 = 0.05/30tests). Individuals with the GG genotype showed a significantly lower mean verbal memory score, compared with those individuals carrying the AA/AG genotype (106.0 +/- 16.0 vs. 111.7 +/- 13.4; p = 0.00099). A haplotype block containing two markers of rs2037639 and rs10860936 was associated with verbal memory index (permutation global p = 0.0091). Conclusions: Our findings suggest that common genetic variations in PAH are associated with verbal memory in healthy adults. Unknown functional polymorphisms in PAH or those in other genes nearby might affect memory performance.


Relationship of temperament and character with cortisol reactivity to the combined dexamethasone/CRH test in depressed outpatients
JOURNAL OF AFFECTIVE DISORDERS,147(1-3):128-136 2013(May)
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Kotaro Hattori; Miyako Hashikura; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Background: Evidence shows that depression is associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, although such findings are not entirely unequivocal. In contrast, various psychiatric conditions, including atypical depression, are associated with hypocortisolism. Another line of research has demonstrated that personality is associated with HPA axis alteration. It is thus hypothesized that different personality pathology in depression would be associated with distinct cortisol reactivity. Methods: Eighty-seven outpatients with DSM-IV major depressive disorder were recruited. Personality was assessed by the temperament and character inventory (TCI). HPA axis reactivity was measured by the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. According to our previous studies, two subgroups were considered based on their cortisol responses to the DEX/CRH test: incomplete-suppressors whose cortisol response was exaggerated and enhanced-suppressors whose cortisol response was blunted. Results: The analysis of covariance, controlling for age, gender and symptom severity, revealed that incomplete-suppressors scored significantly higher on cooperativeness than enhanced-suppressors (p=0.002). A multivariate stepwise logistic regression analysis predicting the cortisol suppression pattern from the seven TCI dimensions, controlling for age, gender and symptom severity, revealed that lower cooperativeness (p=0.001) and higher reward dependence (p=0.018) were significant predictors toward enhanced suppression. Limitations: The neuroendocrine challenge test was administered only once, based on a simple test protocol. Conclusions: Our findings suggest that (personality-related) subtypes of depression might be differentiated based on the different pattern of cortisol reactivity. Future studies are warranted to further characterize the HPA axis alteration in relation to various subtypes of depression. (C) 2012 Elsevier B.V. All rights reserved.


[Personality dimensions in major depressive disorder predict cortisol reactivity to the combined dexamethasone/CRH test].
Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology,33(2):61-63 2013(Apr.)
Author:Hori H; Teraishi T; Sasayama D; Hattori K; Hashikura M; Higuchi T; Kunugi H


Multimodal image analysis of sensorimotor gating in healthy women
BRAIN RESEARCH,1499:61-68 2013(Mar.)
Author:Miho Ota; Noriko Sato; Junko Matsuo; Yukiko Kinoshita; Yumiko Kawamoto; Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Kotaro Hattori; Satoko Obu; Yasuhiro Nakata; Hiroshi Kunugi
Abstract:Prepulse inhibition (PPI) deficits have been reported in individuals with schizophrenia and other psychiatric disorders with dysfunction of the cortico-striato-pallido-thalamic circuit. The purpose of this study was to investigate the structural neural correlates of PPI by using magnetic resonance imaging (MRI) metrics. The subjects were 53 healthy women (mean age; 40.7 +/- 11.3 years). We examined the possible relationships between PPI and diffusion tensor imaging (DTI) metrics to estimate white matter integrity and gray matter volume analyzed using the DARTEL (diffeomorphic anatomical registration through exponentiated lie) algebra method. There were significant correlations between DTI metrics and PPI in the parahippocampal region, the anterior limb of the internal capsule, the ventral tegmental area, the thalamus and anterior thalamic radiations, the left prefrontal region, the callosal commissural fiber, and various white matter regions. There were also positive correlations between PPI and gray matter volume in the bilateral parietal gyri and the left inferior prefrontal gyrus at a trend level. The present study revealed evidence of a relationship between PPI and the integrity of white matter. This result was compatible with the previous suggestion that PPI would be modulated by the cortico-striato-thalamic-pallido-pontine circuit. (c) 2013 Elsevier B.V. All rights reserved.


Identification of Single Nucleotide Polymorphisms Regulating Peripheral Blood mRNA Expression with Genome-Wide Significance: An eQTL Study in the Japanese Population
PLOS ONE,8(1):- 2013(Jan.)
Author:Daimei Sasayama; Hiroaki Hori; Seiji Nakamura; Ryo Miyata; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Noriko Yamamoto; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Several recent studies have reported that expression quantitative trait loci (eQTLs) may affect gene expression in a cell-dependent manner. In the current study, a genome-wide eQTL analysis was performed in whole blood samples collected from 76 Japanese subjects. RNA microarray analysis was performed for 3 independent sample groups that were genotyped in a genome-wide scan. The correlations between the genotypes of 534,404 autosomal single nucleotide polymorphisms (SNPs) and the expression levels of 30,465 probes were examined for each sample group. The SNP-probe pairs with combined correlation coefficients of all 3 sample groups corresponding to P<3.1x10(-12) (i.e., Bonferroni-corrected P<0.05) were considered significant. SNP-probe pairs with a high likelihood of cross-hybridization and SNP-in-probe effects were excluded to avoid false positive results. We identified 102 cis-acting and 5 trans-acting eQTL regions. The cis-eQTL regions were widely distributed both upstream and downstream of the gene, as well as within the gene. The eQTL SNPs identified were examined for their influence on the expression levels in lymphoblastoid cell lines by using a public database. The results showed that genetic variants affecting expression levels in whole blood may have different effects on gene expression in lymphoblastoid cell lines. Further studies are required to clarify how SNPs function in affecting the expression levels in whole blood as well as in other tissues.


[Distinguishing normal women from those with schizophrenia by means of MRI].
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica,115(12):1171-1177 2013
Author:Ota M; Sato N; Ishikawa M; Hori H; Sasayama D; Hattori K; Teraishi T; Obu S; Nakata Y; Nemoto K; Moriguchi Y; Hashimoto R; Kunugi H


The reliability and validity of the Questionnaire - Children with Difficulties (QCD)
CHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH,7:- 2013
Author:Masahide Usami; Daimei Sasayama; Nobuhiro Sugiyama; Nana Hosogane; Soo-Yung Kim; Yushiro Yamashita; Masaki Kodaira; Kyota Watanabe; Yoshitaka Iwadare; Tetsuji Sawa; Kazuhiko Saito
Abstract:Background: The aim of this study was to evaluate the reliability and validity of the Questionnaire-Children with Difficulties (QCD), which was developed for the evaluation of children's daily life behaviors during specified periods of the day. Methods: The subjects were 1,514 Japanese public elementary and junior high school students. For the examination of reliability, Cronbach's alpha was calculated to assess the internal consistency of the questionnaire. With regard to validity, correlation coefficients were calculated to examine whether QCD scores correlated with those of the ADHD-Rating Scale (ADHD-RS) and the Oppositional Defiant Behavior Inventory (ODBI). Results: Cronbach's alpha coefficient for the total score of the QCD was .876. The correlation coefficients of the QCD score with ADHD-RS and ODBI scores were -.514 and -.577, respectively. Conclusions: The internal consistency and validity of the QCD were demonstrated. The QCD is a reliable and valid instrument for evaluating daily life problems for children during different time periods of the day.


PHENYLALANINE KINETICS IN SCHIZOPHRENIA PATIENTS DETECTED BY C-13-PHENYLALANINE BREATH TEST
European Psychiatry,28 2013
Author:Teraishi T; Ozeki Y; Hori H; Sasayama D; Chiba S; Yamamoto N; Tanaka H; Iijima Y; Matsuo J; Kawamoto Y; Kinoshita Y; Hattori K; Ota M; Kajiwara M; Terada S; Higuchi T; Kunugi H


Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder
Journal of Psychiatric Research,47(3):401-406 2013
Author:Daimei Sasayama; Kotaro Hattori; Chisato Wakabayashi; Toshiya Teraishi; Hiroaki Hori; Miho Ota; Sumiko Yoshida; Kunimasa Arima; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027 MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded. © 2012 Elsevier Ltd.


Discrimination between schizophrenia and major depressive disorder by magnetic resonance imaging of the female brain
Journal of Psychiatric Research,47(10):1383-1388 2013
Author:Miho Ota; Masanori Ishikawa; Noriko Sato; Hiroaki Hori; Daimei Sasayama; Kotaro Hattori; Toshiya Teraishi; Takamasa Noda; Satoko Obu; Yasuhiro Nakata; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Background: Although schizophrenia and major depressive disorder (MDD) differ on a variety of neuroanatomical measures, a diagnostic tool to discriminate these disorders has not yet been established. We tried to identify structural changes of the brain that best discriminate between schizophrenia and MDD on the basis of gray matter volume, ventricle volume, and diffusion tensor imaging (DTI). Method: The first exploration sample consisted of 25 female patients with schizophrenia and 25 females with MDD. Regional brain volumes and fractional anisotropy (FA) values were entered into a discriminant analysis. The second validation sample consisted of 18 female schizophrenia and 16 female MDD patients. Results: The stepwise discriminant analysis resulted in correct classification rates of 0.80 in the schizophrenic group and 0.76 in MDD. In the second validation sample, the obtained model yielded correct classification rates of 0.72 in the schizophrenia group and 0.88 in the MDD group. Conclusion: Our results suggest that schizophrenia and MDD have differential structural changes in the examined brain regions and that the obtained discriminant score may be useful to discriminate the two disorders. © 2013 Elsevier Ltd.


Schizotypy and genetic loading for schizophrenia impact upon neuropsychological status in bipolar II and unipolar major depressive disorders
JOURNAL OF AFFECTIVE DISORDERS,142(1-3):225-232 2012(Dec.)
Author:Hiroaki Hori; Junko Matsuo; Toshiya Teraishi; Daimei Sasayama; Yumiko Kawamoto; Yukiko Kinoshita; Kotaro Hattori; Miyako Hashikura; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Background: Growing evidence suggests that schizotypy and genetic loading for schizophrenia both represent risk for the development of schizophrenia. Although these conditions are known to be associated with neurocognitive impairments, such an association has not been studied in patients with bipolar II disorder (BPII) or unipolar major depressive disorder (UP). Methods: Forty-one depressed patients with BPII, 131 patients with UP and demographically matched 225 healthy controls were recruited. Schizotypy was assessed by the Schizotypal Personality Questionnaire. Neuropsychological functioning was measured by the Wechsler Memory Scale-Revised, the Wechsler Adult Intelligence Scale-Revised and the Wisconsin Card Sorting Test. Results: Mood disorder patients performed significantly worse than controls in verbal and visual memory, working memory and processing speed. BPII patients performed significantly more poorly than UP patients in verbal memory and executive functioning. Both BPII and UP patients demonstrated significantly greater schizotypal traits than controls. Schizotypy was significantly negatively correlated with verbal comprehension both in BPII and UP patients and with working memory and processing speed in healthy controls. Patients who had one or more first-degree relatives with schizophrenia performed significantly more poorly than the remaining patients in all cognitive domains. Limitations: Most of our patients were on psychotropic medication, and the sample of BPII patients was not very large. Conclusions: Liability for schizophrenia could play a pivotal role in neurocognitive functioning in mood disorders, suggesting that such liability might lie on a continuum ranging from normality through mood disorders to full-blown schizophrenia. (C) 2012 Elsevier B.V. All rights reserved.


Schizotypal trait in healthy women is associated with a shift away from dextrality on a spatial motor control task, but not on a force control task
PSYCHIATRY RESEARCH,200(2-3):629-634 2012(Dec.)
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Kotaro Hattori; Miho Ota; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Hiroshi Kunugi
Abstract:It is generally acknowledged that schizophrenia and schizotypy lie on the same continuum, while there is an ongoing debate as to whether schizotypy represents true dimension or quasi-dimension. Evidence suggests that reduced hemispheric lateralization and mixed handedness are associated with both schizophrenia and schizotypy. However, the possible relationship of schizotypy with laterality as assessed with motor function tasks has not been well documented. A few studies using fine motor control tasks have demonstrated the relationship between schizotypy and reduced laterality among student populations, yet little has been done in community samples. Here we employed 249 healthy women and examined the association between schizotypal traits assessed with the Schizotypal Personality Questionnaire and motor functions assessed with the Purdue Pegboard test (as a measure of spatial motor control) and a handgrip force test. Correlational and categorical analyses both showed that schizotypal traits were significantly associated with leftward and bilateral bias in the fine motor control task, but not in the handgrip force test. Schizotypy did not significantly affect the performance level on either of these tasks. These results indicate that schizotypal traits in healthy women are associated with a shift away from dextrality, supporting the fully dimensional model of schizotypy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.


Discrimination of female schizophrenia patients from healthy women using multiple structural brain measures obtained with voxel-based morphometry
PSYCHIATRY AND CLINICAL NEUROSCIENCES,66(7):611-617 2012(Dec.)
Author:Miho Ota; Noriko Sato; Masanori Ishikawa; Hiroaki Hori; Daimei Sasayama; Kotaro Hattori; Toshiya Teraishi; Satoko Obu; Yasuhiro Nakata; Kiyotaka Nemoto; Yoshiya Moriguchi; Ryota Hashimoto; Hiroshi Kunugi
Abstract:Aim Although schizophrenia and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between the two groups are low. To identify the correlative pattern of brain changes that best discriminate schizophrenia patients from healthy subjects, discriminant analysis techniques using voxel-based morphometry were applied. Methods The first analysis was conducted to obtain a statistical model that classified 105 female healthy subjects and 38 female schizophrenia patients. First, the differences in gray matter and cerebrospinal fluid volume between the patients and healthy subjects were evaluated using optimized voxel-based morphometry. Then, a discriminant analysis reflecting the results of this evaluation was adopted. The second analysis was performed to prospectively validate the statistical model by successfully classifying a new group that consisted of 23 female healthy subjects and 23 female schizophrenia patients. Results The use of these variables resulted in correct classification rates of 0.72 in the control subjects and 0.76 in the schizophrenia patients. In the second validation analysis using these variables, correct classification rates of 0.70 in the control subjects and 0.74 in the schizophrenia patients were achieved. Conclusion Schizophrenia patients have structural deviations in multiple brain areas, and a combination of structural brain measures can distinguish between patients and controls.


Poor performance on the Iowa gambling task in children with obsessive-compulsive disorder
ANNALS OF GENERAL PSYCHIATRY,11:- 2012(Oct.)
Author:Masaki Kodaira; Yoshitaka Iwadare; Hirokage Ushijima; Arata Oiji; Motoichiro Kato; Nobuhiro Sugiyama; Daimei Sasayama; Masahide Usami; Kyota Watanabe; Kazuhiko Saito
Abstract:Background: Several lines of evidence implicate orbitofrontal cortex dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of this study was to investigate neuropsychological dysfunction of the orbitofrontal cortex in children with OCD. Methods: The Iowa Gambling Task (IGT), which reflects orbitofrontal cortex function, and the Wisconsin Card Sorting Test (WCST), which is associated with functioning of the dorsolateral prefrontal cortex, were administered to 22 children with OCD and 22 healthy controls matched for gender, age, and intelligence. Results: OCD patients displayed poor performance on the IGT. In contrast, performance on the WCST was not impaired in OCD patients compared to controls. Conclusions: These findings are in line with previous studies demonstrating that OCD in childhood is associated with a dysfunction of orbitofrontal-striatal-thalamic circuitry.


Effects of the CACNA1C risk allele on neurocognition in patients with schizophrenia and healthy individuals
SCIENTIFIC REPORTS,2:- 2012(Sep.)
Author:Hiroaki Hori; Noriko Yamamoto; Takashi Fujii; Toshiya Teraishi; Daimei Sasayama; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Miho Ota; Kotaro Hattori; Masahiko Tatsumi; Kunimasa Arima; Hiroshi Kunugi
Abstract:Recent genetic association studies have identified the A-allele of rs1006737 within CACNA1C as a risk factor for schizophrenia as well as mood disorders. Some evidence suggests that this polymorphism plays a role in cognitive function both in schizophrenia patients and healthy individuals; however, the precise nature of this association remains unclear. Here we investigated the possible association of this polymorphism with a wide range of neurocognitive functions in schizophrenia patients and in healthy subjects. Schizophrenia patients exhibited significantly poorer performance on all the cognitive domains as compared to healthy controls. In patients, A-allele carriers demonstrated significantly worse logical memory performance than the G-allele homozygotes. In controls, no significant association was observed between the genotype and any of the cognitive domains examined. These results add to the literature suggesting that rs1006737 may be associated with schizophrenia through its detrimental effect on endophenotypic traits.


Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY,38(2):341-344 2012(Aug.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Masahiko Tatsumi; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Background: The beta 3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression. Methods: The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MOD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls. Results: No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027). Conclusions: We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity. (C) 2012 Elsevier Inc. All rights reserved.


Negative correlation between cerebrospinal fluid oxytocin levels and negative symptoms of male patients with schizophrenia
SCHIZOPHRENIA RESEARCH,139(1-3):201-206 2012(Aug.)
Author:Daimei Sasayama; Kotaro Hattori; Toshiya Teraishi; Hiroaki Hori; Miho Ota; Sumiko Yoshida; Kunimasa Arima; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Background: Accumulating evidence indicates that oxytocin plays an important role in social interactions. Previous studies also suggest altered oxytocin function in patients with schizophrenia and depression. However, few studies have examined the central oxytocin levels in these disorders. Methods: Cerebrospinal fluid (CSF) oxytocin levels were measured by ELISA in male participants consisting of 27 patients with schizophrenia, 17 with major depressive disorder (MDD), and 21 healthy controls. Results: CSF oxytocin levels of patients with schizophrenia or MDD did not differ significantly with healthy controls. The antidepressant dose or the Hamilton depression rating scale score did not significantly correlate with the oxytocin levels in MDD patients. CSF oxytocin levels in schizophrenic patients significantly negatively correlated with second generation antipsychotic dose (r=-0.49, P=0.010) but not with first generation antipsychotic dose (r=-0.13, P=0.50). A significant correlation was observed between oxytocin levels and negative subscale of PANSS (r=-0.38, P=0.050). This correlation remained significant even after controlling for second generation antipsychotic dose (r=-0.47, P=0.016). Conclusions: We obtained no evidence of altered CSF oxytocin levels in patients with schizophrenia or those with MDD. However, lower oxytocin levels may be related to higher second generation antipsychotic dose and more severe negative symptoms in schizophrenia. (C) 2012 Elsevier B.V. All rights reserved.


Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation
ACTA PSYCHIATRICA SCANDINAVICA,126(1):72-78 2012(Jul.)
Author:M. Ota; M. Ishikawa; N. Sato; H. Hori; D. Sasayama; K. Hattori; T. Teraishi; Y. Nakata; H. Kunugi
Abstract:Ota M, Ishikawa M, Sato N, Hori H, Sasayama D, Hattori K, Teraishi T, Nakata Y, Kunugi H. Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation. Objective: Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. This study was aimed to examine several brain chemical mediators, including Glx (glutamate + glutamine), using 1H magnetic resonance spectroscopy (MRS) in medicated patients with schizophrenia, with and without psychotic exacerbation. Method: 1H MRS was acquired in 24 patients with schizophrenia, with psychotic exacerbation; 22 patients without exacerbation; and 27 age- and sex-matched healthy volunteers. The levels of metabolites were measured in the left frontal and inferior parietal white matter and compared across the three groups. Results: The Glx level was significantly elevated in the left inferior parietal white matter in the patients with psychotic exacerbation in comparison with that in the healthy volunteers and the patients without exacerbation (P < 0.05). We also detected that there was a significant correlation between Positive and Negative Syndrome Scale-positive scale and Glx level in the left parietal white matter (r = 0.51, P < 0.001). Conclusion: Higher than normal Glx levels indicate glutamatergic overactivity in the left inferior parietal white matter with schizophrenic exacerbation, a finding that is in accordance with the glutamatergic hypothesis in schizophrenia. The Glx level measured by 1H MRS could be a biomarker for exacerbation in schizophrenia.


C-13-phenylalanine breath test detects altered phenylalanine kinetics in schizophrenia patients
TRANSLATIONAL PSYCHIATRY,2(2):e119 2012(May)
Author:T. Teraishi; Y. Ozeki; H. Hori; D. Sasayama; S. Chiba; N. Yamamoto; H. Tanaka; Y. Iijima; J. Matsuo; Y. Kawamoto; Y. Kinoshita; K. Hattori; M. Ota; M. Kajiwara; S. Terada; T. Higuchi; H. Kunugi
Abstract:Phenylalanine is an essential amino acid required for the synthesis of catecholamines including dopamine. Altered levels of phenylalanine and its metabolites in blood and cerebrospinal fluid have been reported in schizophrenia patients. This study attempted to examine for the first time whether phenylalanine kinetics is altered in schizophrenia using L-[1-C-13]phenylalanine breath test (C-13-PBT). The subjects were 20 chronically medicated schizophrenia patients (DSM-IV) and the same number of age- and sex-matched controls. C-13-phenylalanine (99 atom% C-13; 100mg) was administered orally and the breath (CO2)-C-13/(CO2)-C-12 ratio was monitored for 120 min. The possible effect of antipsychotic medication (risperidone (RPD) or haloperidol (HPD) treatment for 21 days) on C-13-PBT was examined in rats. Body weight (BW), age and diagnostic status were significant predictors of the area under the curve of the time course of triangle(CO2)-C-13 (parts per thousand) and the cumulative recovery rate (CRR) at 120 min. A repeated measures analysis of covariance controlled for age and BW revealed that the patterns of CRR change over time differed between the patients and controls and that triangle(CO2)-C-13 was lower in the patients than in the controls at all sampling time points during the 120 min test, with an overall significant difference between the two groups. Chronic administration of RPD or HPD had no significant effect on C-13-PBT indices in rats. Our results suggest that C-13-PBT is a novel laboratory test that can detect altered phenylalanine kinetics in chronic schizophrenia patients. Animal experiments suggest that the observed changes are unlikely to be attributable to antipsychotic medication. Translational Psychiatry (2012) 2, e119; doi:10.1038/tp.2012.48; published online 22 May 2012


13C-phenylalanine breath test detects altered phenylalanine kinetics in schizophrenia patients
Translational Psychiatry,22(2):e119 2012(May)
Author:Teraishi T, Ozeki Y, Hori H, Sasayama D, Chiba S, Yamamoto N, Tanaka H, Iijima Y, Matsuo J, Kawamoto Y, Kinoshita Y, Hattori K, Ota M, Kajiwara M, Terada S, Higuchi T, Kunugi H
Abstract:Translational Psychiatry


Schizotypy and Genetic Loading for Schizophrenia Impact Upon Neuropsychological Status in Bipolar II and Unipolar Major Depressive Disorders
BIOLOGICAL PSYCHIATRY,71(8):88S-88S 2012(Apr.)
Author:Hiroaki Hori; Junko Matsuo; Toshiya Teraishi; Daimei Sasayama; Yumiko Kawamoto; Yukiko Kinoshita; Kotaro Hattori; Miyako Hashikura; Teruhiko Higuchi; Hiroshi Kunugi


SCHIZOTYPY AND GENETIC LOADING FOR SCHIZOPHRENIA IMPACT UPON NEUROPSYCHOLOGICAL STATUS IN BIPOLAR II AND UNIPOLAR MAJOR DEPRESSIVE DISORDERS
SCHIZOPHRENIA RESEARCH,136:S330-S331 2012(Apr.)
Author:Hori, Hiroaki; Matsuo, Junko; Teraishi, Toshiya; Sasayama, Daimei; Kawamoto, Yumiko; Kinoshita, Yukiko; Hattori, Kotaro; Hashikura, Miyako; Higuchi, Teruhiko; Kunugi, Hiroshi;


INTERLEUKIN-6 LEVELS IN CEREBROSPINAL FLUID OF PATIENTS WITH SCHIZOPHRENIA
SCHIZOPHRENIA RESEARCH,136:S230-S230 2012(Apr.)
Author:Daimei Sasayama; Kotaro Hattori; Haruko Tanaka; Hiroaki Hori; Toshiya Teraishi; Miho Ota; Naoji Amano; Hiroshi Kunugi


Association between the functional polymorphism (C3435T) of the gene encoding P-glycoprotein (ABCB1) and major depressive disorder in the Japanese population
JOURNAL OF PSYCHIATRIC RESEARCH,46(4):555-559 2012(Apr.)
Author:Takashi Fujii; Miho Ota; Hiroaki Hori; Daimei Sasayama; Kotaro Hattori; Toshiya Teraishi; Noriko Yamamoto; Miyako Hashikura; Masahiko Tatsumi; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Human P-glycoprotein (P-gp), which is encoded by ABCB1 (ATP-binding cassette, sub-family B member 1), is expressed in the blood brain barrier and protects the brain from many kinds of drugs and toxins including glucocorticoids by acting as an efflux pump. We examined whether functional polymorphisms of ABCB1 give susceptibility to major depressive disorder (MDD). The five functional single nucleotide polymorphisms (SNPs), A-41G (rs2188524), T-129C (rs3213619), C1236T (Gly412Gly: rs1128503). G2677A/T (Ala893Ser/Thr: rs2032582), and C3435T (Ile1145Ile: rs1045642) were genotyped in 631 MOD patients and 1100 controls in the Japanese population. A tri-allelic SNP, G2677A/T, was genotyped by pyrosequencing and the remaining SNPs were genotyped by the TaqMan 5'-exonuclease allelic discrimination assay. The minor T3435 allele was significantly increased in MDD patients than in the controls (chi(2) = 4.5, df = 1, p = 0.034, odds ratio [OR] 1.16, 95% confidential interval [CI] 1.01-1.34). Homozygotes for the T3435 allele was significantly more common in patients than in the controls (chi(2) = 7.5, df = 1, p = 0.0062, OR 1.43, 95%CI 1.11-1.85). With respect to the other 4 SNPs, there was no significant difference in genotype or allele distribution. In the haplotype-based analysis, the proportion of individuals with the TT1236-TT3435 haploid genotype was significantly increased in patients than in controls (chi(2) = 8.5, df = 1, p = 0.0037, OR 1.50, 95%CI 1.14-1.98). Our results suggest that the T3435 allele or carrying two copies of this allele confers susceptibility to MOD in the Japanese population. (C) 2012 Elsevier Ltd. All rights reserved.


ANALYSES OF MONOAMINE METABOLITES IN THE CEREBROSPINAL FLUID OF PATIENTS WITH SCHIZOPHRENIA
SCHIZOPHRENIA RESEARCH,136:S137-S137 2012(Apr.)
Author:Kotaro Hattori; Daimei Sasayama; Toshiya Teraishi; Takashi Fujii; Hiroshi Kunugi


Association of cognitive performance with interleukin-6 receptor Asp358Ala polymorphism in healthy adults
JOURNAL OF NEURAL TRANSMISSION,119(3):313-318 2012(Mar.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Naoji Amano; Hiroshi Kunugi
Abstract:Wechsler adult intelligence scale-revised was performed in 576 healthy adults to examine whether a functional polymorphism (Asp358Ala) of the IL-6 receptor (IL-6R) gene is associated with cognitive performance. Verbal intelligence quotient in Asp homozygotes was significantly higher compared to Ala carriers (P = 0.005). Compared to Ala carriers, Asp homozygotes performed better in the verbal subtests requiring long-term memory stores. Elevated IL-6 and soluble IL-6R levels in Ala carriers may have negative impact on acquiring verbal cognitive ability requiring long-term memory.


More severe impairment of manual dexterity in bipolar disorder compared to unipolar major depression
JOURNAL OF AFFECTIVE DISORDERS,136(3):1047-1052 2012(Feb.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Miyako Hashikura; Naoji Amano; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Background: Mood disorders are associated with various neurocognitive deficits. However, few studies have reported the impairment of motor dexterity in unipolar depression and bipolar disorder. In the present study, manual dexterity was compared between unipolar major depression, bipolar disorder, and healthy controls. Methods: Manual dexterity was assessed by the Purdue pegboard test in 98 patients with unipolar major depression, 48 euthymic or depressed patients with bipolar disorder, and 158 healthy controls, matched for age and gender. Results: Compared to healthy controls, sum of the scores of right, left, and both hands subtests (R + L+ B) was significantly lower in both patients with unipolar depression and bipolar disorder (P= 0.0034 and P<0.0001, respectively). Furthermore, R + L + B was significantly lower in bipolar disorder compared to unipolar depression (P=0.0016). Lithium dose and chlorpromazine equivalent dose of antipsychotics were significantly negatively correlated with some of the subtest scores. On the other hand, depression severity did not significantly correlate with any of the subtest scores. Difference in R + L+ B between unipolar depression and bipolar disorder remained statistically significant even after controlling for gender, age, lithium dose, and chlorpromazine equivalent dose (P = 0.0028). Limitations Bipolar patients during manic episode were not included in the study. Conclusions: Gross movement dexterity was impaired in both patients with unipolar depression and bipolar disorder. The severity of impairment was significantly greater in patients with bipolar disorder. The functional difference between unipolar and bipolar patients may suggest different pathological conditions between the two depressive disorders. (C) 2011 Elsevier B.V All rights reserved.


Relationships between season of birth, schizotypy, temperament, character and neurocognition in a non-clinical population
PSYCHIATRY RESEARCH,195(1-2):69-75 2012(Jan.)
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Hiroshi Kunugi
Abstract:While schizophrenia has been associated with a slight excess of winter/early spring birth, it is unclear whether there is such an association in relation to schizotypal personality traits. Season of birth has also been reported to relate to temperament and character personality dimensions and cognitive functioning. Moreover, non-clinical schizotypy has been shown to be associated with mild cognitive impairment, although its precise nature is yet to be elucidated. Here we examined the relationships between season of birth, schizotypal traits, temperament and character, and cognitive function. Four hundred and fifty-one healthy adults completed the Schizotypal Personality Questionnaire (SPQ). The Temperament and Character Inventory (TCI) and a neuropsychological test battery consisting of full versions of the Wechsler Memory Scale-Revised and the Wechsler Adult Intelligence Scale-Revised, and the Wisconsin Card Sorting Test, were also administered to most of the participants. The total SPQ score of those born in winter was significantly higher than that of the remaining participants. Season of birth was not significantly associated with any of the TCI dimensions or cognitive test results. Significant but mild relationships between higher SPQ scores and lower scores on some aspects of IQ were observed. These results support the notion that schizotypy and schizophrenia are neurodevelopmental conditions on the same continuum. (C) 2011 Elsevier Ireland Ltd. All rights reserved.


Schizotypy and genetic loading for schizophrenia impact upon neuropsychological status in bipolar II and unipolar major depressive disorders
JOURNAL OF AFFECTIVE DISORDERS,142(1-3):225-232 2012
Author:Hori, Hiroaki; Matsuo, Junko; Teraishi, Toshiya; Sasayama, Daimei; Kawamoto, Yumiko; Kinoshita, Yukiko; Hattori, Kotaro; Hashikura, Miyako; Higuchi, Teruhiko; Kunugi, Hiroshi;


Elevated cortisol level and cortisol/DHEAS ratio in schizophrenia as revealed by low-dose dexamethasone suppression test
Open Neuropsychopharmacology Journal,5(1):18-28 2012
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Takashi Fujii; Kotaro Hattori; Masanori Ishikawa; Hiroshi Kunugi
Abstract:Earlier studies have used the dexamethasone (DEX) suppression test (DST) to investigate the hypothalamicpituitary- adrenal (HPA) function in schizophrenia, although the findings are controversial. Recently there has been an increased interest in the role of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in HPA axis function. Several studies have investigated basal DHEA(S) levels and cortisol/DHEA(S) ratios in schizophrenia patients, while no attempts have been made to investigate DHEA(S) level in response to the DEX administration. We aimed to compare the post- DEX cortisol and DHEAS levels and the cortisol/DHEAS ratio between schizophrenia patients and healthy controls. Here we administered the DST to 43 patients with schizophrenia and 37 age- and sex-matched healthy controls. Plasma cortisol levels, serum DHEAS levels, and cortisol/DHEAS ratio after administration of 0.5 mg of DEX were compared between the two groups. Schizophrenia patients showed significantly higher cortisol level and cortisol/DHEAS ratio than controls, while DHEAS levels were not significantly different between groups. These results suggest that besides the cortisol level, cortisol/DHEAS ratio as assessed with the DST might reflect abnormal HPA axis function in schizophrenia. © Hori et al.


Support for association between the Ser205Leu polymorphism of p75(NTR) and major depressive disorder
JOURNAL OF HUMAN GENETICS,56(11):806-809 2011(Nov.)
Author:Takashi Fujii; Noriko Yamamoto; Hiroaki Hori; Kotaro Hattori; Daimei Sasayama; Toshiya Teraishi; Miyako Hashikura; Masahiko Tatsumi; Nagahisa Okamoto; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Altered neurotrophin functions have been implicated in major depressive disorder (MDD). Previously, we reported an association between MDD and a missense polymorphism (Ser205Leu: rs2072446) of the gene encoding the p75 neurotrophin receptor (p75(NTR)). However, contradictive negative results have also been reported. This study tried to replicate the association in an independent sample. Subjects were 668 patients with MDD and 1130 healthy controls. The proportion of individuals carrying the Leu205 allele was significantly decreased in the patients than in the controls (chi(2)=5.3, d.f.=1, P=0.021, odds ratio (OR) 0.74, 95% confidential interval (CI) 0.58-0.96). When allele frequencies were compared, the Leu205 allele was significantly reduced in the patients than in the controls (chi(2)= 4.4, d.f.=1, P=0.037, OR=0.78, 95% CI=0.61-0.99). When men and women were examined separately, there was a significant difference in genotype and allele distributions in women (genotype: chi(2)=8.3, d.f.=1, P=0.0039, OR=0.60, 95% CI=0.43-0.85; allele: chi(2)=7.3, d.f.=1, P 0.0069, OR=0.64, 95% CI=0.47-0.89), but not in men. The present study provided support for the previously reported association between the Ser205Leu polymorphism of the p75NTR gene and MDD, indicating that the Leu205 allele has a protective effect against the development of MDD, particularly in women. Journal of Human Genetics (2011) 56, 806-809; doi: 10.1038/jhg.2011.107; published online 22 September 2011


Association of plasma IL-6 and soluble IL-6 receptor levels with the Asp358Ala polymorphism of the IL-6 receptor gene in schizophrenic patients
JOURNAL OF PSYCHIATRIC RESEARCH,45(11):1439-1444 2011(Nov.)
Author:Daimei Sasayama; Chisato Wakabayashi; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Masanori Ishikawa; Kunimasa Arima; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Recent studies indicate a role of excessive interleukin-6 (IL-6) signaling in the pathogenesis of schizophrenia. A previous study reported a significant association of schizophrenia with the IL-6 receptor (IL-6R) gene Asp358Ala polymorphism, which is known to regulate circulating IL-6 and soluble IL-6R (sIL-6R) levels in healthy subjects. To further examine the influence of the polymorphism in schizophrenic patients, we compared the plasma levels of IL-6 and sIL-6R between schizophrenic patients and healthy controls for each genotype of the Asp358Ala polymorphism. Asp358Ala genotyping and plasma IL-6 level measurements were performed in 104 patients with schizophrenia and 112 healthy controls. Of these participants, 53 schizophrenic patients and 49 controls were selected for the measurement of plasma sIL-6R levels. A two-way factorial analysis of covariance was performed with the transformed plasma levels as the dependent variable, diagnosis and genotype as independent variables, and sex and age as covariates. No significant diagnosis x genotype interaction was observed for IL-6 and sIL-6R levels. The Ala allele of Asp358Ala was significantly associated with higher levels of both IL-6 and sIL-6R. IL-6 levels were significantly elevated in schizophrenic patients compared to those in controls, whereas no significant difference in sIL-6R levels was observed between schizophrenic patients and controls. Our findings suggest that the presence of schizophrenia is associated with elevated IL-6 levels, whereas sIL-6R levels are mainly predetermined by the Asp358Ala genotype and are not associated with the disease status. Increased IL-6 levels without alterations in sIL-6R levels may result in excessive IL-6 signaling in schizophrenia. (C) 2011 Elsevier Ltd. All rights reserved.


Poor sleep is associated with exaggerated cortisol response to the combined dexamethasone/CRH test in a non-clinical population
JOURNAL OF PSYCHIATRIC RESEARCH,45(9):1257-1263 2011(Sep.)
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Yuji Ozeki; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Kotaro Hattori; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Although sleep disturbance has been shown to be associated with psychological distress and the hypothalamic-pituitary-adrenal (HPA) axis function, the simultaneous relationship between sleep, distress and HPA axis function is less clear. Here we examined the relationship between sleep quality as assessed with the Pittsburgh Sleep Quality Index, psychological distress as assessed with the Hopkins Symptom Checklist, and cortisol responses to the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test in 139 non-clinical volunteers. Poor sleep was significantly correlated with greater cortisol response to the combined DEX/CRH challenge, but riot with the cortisol level just before CRH challenge. When subjects were divided into three groups based on the suppression pattern of cortisol (i.e., incomplete-, moderate-, and enhanced-suppressors), poor sleep was significantly associated with the incomplete suppression in women while no significant association was found between sleep and the enhanced suppression. The association between poor sleep and exaggerated cortisol response to the CRH challenge became more clear in the regression analysis where the confounding effect of psychological distress was taken into consideration. These results indicate that poor sleep would be associated with exaggerated cortisol reactivity. The observed association of poor sleep with reactive cortisol indices to the CRH challenge, but not with the cortisol level after DEX administration alone, might add to the well-established evidence demonstrating the role of CRH in the regulation of sleep. Our findings further suggest that the mediation model would work better than the bivariate approach in investigating the relationship between sleep, distress and HPA axis reactivity. (C) 2011 Elsevier Ltd. All rights reserved.


Possible association between Interleukin-1beta gene and schizophrenia in a Japanese population
BEHAVIORAL AND BRAIN FUNCTIONS,7:- 2011(Aug.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Yoshimi Iijima; Masahiko Tatsumi; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Background: Several lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1 beta) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms. Methods: A total of 533 patients with schizophrenia (302 males: mean age +/- standard deviation 43.4 +/- 13.0 years; 233 females; mean age 44.8 +/- 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 +/- 17.3 years; 748 females; 46.3 +/- 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1 beta gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia. Results: Significant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032). Conclusions: The present study shows the first evidence that the IL-1 beta gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1 beta gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1 beta in the etiology of schizophrenia.


Difference in Temperament and Character Inventory scores between depressed patients with bipolar II and unipolar major depressive disorders
JOURNAL OF AFFECTIVE DISORDERS,132(3):319-324 2011(Aug.)
Author:Daimei Sasayama; Hiroaki Hon; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Miyako Hashikura; Norie Koga; Nagahisa Okamoto; Kota Sakamoto; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Background: Although some core personality variables are known to be characteristic of unipolar or bipolar depression, few studies have compared the personality profile between these two disorders. Methods: Temperament and Character Inventory (TCI) was employed to assess the personality of 36 depressed patients with bipolar II disorder (BPII), 90 patients with unipolar major depressive disorder (UP), and 306 healthy controls. The TCI was administered during the depressive episode in BPII and UP patients so that the results can be applied in a clinical setting. Results: Significantly higher scores in harm avoidance (p<0.0001) and lower scores in self-directedness (p<0.0001) and cooperativeness (p<0.05) were observed in both BPII and UP patients compared to controls. Lower novelty seeking in UP patients compared to BPII patients and controls was observed in females (p<0.0001, p<0.01. respectively). A significant difference in self-transcendence score was observed between BPII and UP patients in females (p<0.0005), with higher scores in BPII (p = 0.009) and lower scores in UP (p = 0.046) patients compared to controls. A logistic regression model predicted BPII in depressed females based on novelty seeking and self-transcendence scores with a sensitivity of 89% and a specificity of 73%, but did not accurately predict BPII in males. Limitations: Patients in our study were limited to those receiving outpatient treatments, and bipolar patients were limited to those with BPII. Conclusions: Novelty seeking and self-transcendence scores of TCI might be useful in the differentiation of UP and BPII in female patients. (C) 2011 Elsevier B.V. All rights reserved.


Association of interleukin-1 beta genetic polymorphisms with cognitive performance in elderly females without dementia
JOURNAL OF HUMAN GENETICS,56(8):613-616 2011(Aug.)
Author:Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Interleukin-1 beta (IL-1 beta) is considered to have a role in age-related cognitive decline. A recent study has shown that a promoter polymorphism of the IL-1 beta gene (rs16944) is associated with cognitive performance in elderly males without dementia. In this study, we examined whether polymorphisms of the IL-1 beta gene also influence cognitive functions in elderly females. Cognitive functions were assessed by the Wechsler adult intelligence scale-revised (WAIS-R) in 99 elderly (>= 60 years) females without dementia. We selected five tagging polymorphisms from the IL-1 beta gene and examined the associations with the WAIS-R scores. Significant associations were found between verbal intelligence quotient (IQ) and the genotypes of rs1143634 and rs1143633 (P = 0.0037 and P = 0.010, respectively). No significant associations of rs16944 genotype were found with verbal or performance IQ. However, individuals homozygous for the G allele of rs16944 achieved higher scores in digit span compared with their counterpart, which is consistent with the previous findings in males. These results suggest that IL-1 beta gene variation may have a role in cognitive functions in aging females as well as males. Journal of Human Genetics (2011) 56, 613-616; doi:10.1038/jhg.2011.56; published online 26 May 2011


Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults
BEHAVIORAL AND BRAIN FUNCTIONS,7:- 2011(Jul.)
Author:Daimei Sasayama; Hiroaki Hori; Yoshimi Iijima; Toshiya Teraishi; Kotaro Hattori; Miho Ota; Takashi Fujii; Teruhiko Higuchi; Naoji Amano; Hiroshi Kunugi
Abstract:Background: Recently, hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944) in the interleukin-1beta (IL-1 beta) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between IL-1 beta gene polymorphisms and HPA axis function assessed with the DEX/CRH test. Methods: DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 +/- 15.8 years; 134 females: mean age 47.1 +/- 13.2 years). Five tagging single nucleotide polymorphisms (SNPs) of IL-1 beta gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r(2) threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA) was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, P values < 0.01 were considered statistically significant for associations between the genotypes and the cortisol levels. Results: The cortisol levels after DEX administration (DST-Cortisol) showed significant associations with the genotypes of rs16944 (P = 0.00049) and rs1143633 (P = 0.0060), with no significant gender effect or genotype x gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol) were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype x gender interaction. Conclusions: Our results suggest that genetic variations in the IL-1 beta gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1 beta gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into the communication between the immune system and the HPA axis.


POLYMORPHISMS OF THE INTERLEUKIN-6 RECEPTOR GENE AND PLASMA LEVELS OF INTERLEUKIN-6 AND SOLUBLE INTERLEUKIN-6 RECEPTOR IN SCHIZOPHRENIA
SCHIZOPHRENIA BULLETIN,37:77-77 2011(Mar.)
Author:Daimei Sasayama; Chisato Wakabayashi; Yoshimi Iijima; Takashi Fujii; Masahiko Tatsumi; Hiroshi Kunugi


ELEVATED CORTISOL LEVELS AND CORTISOL/DEHYDROEPIANDROSTERONE RATIO IN SCHIZOPHRENIA AS REVEALED BY THE DEXAMETHASONE SUPPRESSION TEST
SCHIZOPHRENIA BULLETIN,37:116-116 2011(Mar.)
Author:Hiroaki Hori; Toshiya Teraishi; Daimei Sasayama; Masanori Ishikawa; Teruhiko Higuchi; Hiroshi Kunugi


Schizotypal Personality in Healthy Adults Is Related to Blunted Cortisol Responses to the Combined Dexamethasone/Corticotropin-Releasing Hormone Test
NEUROPSYCHOBIOLOGY,63(4):232-241 2011
Author:Hiroaki Hori; Toshiya Teraishi; Yuji Ozeki; Kotaro Hattori; Daimei Sasayama; Junko Matsuo; Yumiko Kawamoto; Yukiko Kinoshita; Teruhiko Higuchi; Hiroshi Kunugi
Abstract:Background/Aims: Schizotypy is viewed as a dimensional trait ranging from healthy people to schizophrenic spectrum patients. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and accumulated evidence suggests that schizophrenia is associated with altered HPA axis function; however, HPA axis function in relation to schizotypal personality has not been well documented. Methods: We examined the relationship between schizotypal traits as assessed with the Schizotypal Personality Questionnaire (SPQ) and cortisol responses to the combined dexamethasone/corticotropin-releasing hormone test in 141 healthy volunteers. Subjects were divided into three groups based on their cortisol responses to the dexamethasone/corticotropin-releasing hormone test: incomplete suppressors, moderate suppressors, and enhanced suppressors. SPQ scores were compared between these three groups using the analysis of covariance, controlling for age and sex. Results: The analysis of covariance showed significant main effects of the suppressor status on the ideas of reference and suspiciousness/paranoid ideation subscales and cognitive-perceptual factor. Post-hoc analyses with Bonferroni correction revealed that the enhanced suppressors scored significantly higher than the moderate suppressors on these SPQ indices. Conclusion: These results indicate that nonclinical schizotypal traits in healthy adults are associated with blunted cortisol reactivity, potentially suggesting a shared neuroendocrinological mechanism across schizophrenia spectrum pathology. Copyright (C) 2011 S. Karger AG, Basel


Association analysis of the Ser205Leu polymorphism of p75NTR with major depressive disorder
NEUROSCIENCE RESEARCH,71:E304-E304 2011
Author:Takashi Fujii; Noriko Yamamoto; Hiroaki Hori; Kotaro Hattori; Daimei Sasayama; Toshiya Teraishi; Miyako Hashikura; Masahiko Tatsumi; Nagahisa Okamoto; Teruhiko Higuchi; Hiroshi Kunugi


Psychotic symptoms complicate the clinical differentiation of Parkinson's disease with major depressive disorder from dementia with Lewy bodies
PSYCHOGERIATRICS,10(2):107-111 2010(Jun.)
Author:Mitsuhiro Miyashita; Daimei Sasayama; Nobuhiro Sugiyama; Takehiko Yasaki; Shinsuke Washizuka; Naoji Amano
Abstract:Dementia with Lewy bodies (DLB) is diagnosed clinically according to the diagnostic criteria in the Third Report of the DLB Consortium. However, psychotic symptoms, such as visual hallucinations, delusions, and stupor, may complicate the clinical diagnosis of DLB. The present study reports on a patient with Parkinson's disease that was difficult to distinguish from DLB because of the presence of various psychotic symptoms. In making a diagnosis of DLB, it is important to assess essential psychiatric features and to observe patients for any changes in these features.


PLASMA LEVELS AND GENETIC POLYMORPHISMS OF INTERLEUKIN 6 AND INTERLEUKIN 10 IN SCHIZOPHRENIA
SCHIZOPHRENIA RESEARCH,117(2-3):452-453 2010(Apr.)
Author:Daimei Sasayama; Chisato Wakabayashi; Hirofumi Uchiyama; Yoshimi Iijima; Takashi Fujii; Hiroshi Kunugi


Neuroanatomical correlates of attention-deficit-hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder
PSYCHIATRY AND CLINICAL NEUROSCIENCES,64(4):394-402 2010
Author:Daimei Sasayama; Ayako Hayashida; Hidenori Yamasue; Yuzuru Harada; Tomoki Kaneko; Kiyoto Kasai; Shinsuke Washizuka; Naoji Amano
Abstract:Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention-deficit-hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel-based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age-and gender-matched typically developing subjects underwent high-spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel-by-voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.


Analysis of plasma cytokine level and cytokine-related genetic polymorphism in schizophrenia
NEUROSCIENCE RESEARCH,68:E84-E84 2010
Author:Chisato Wakabayashi; Daimei Sasayama; Hiroshi Kunugi


High prevalence of pervasive developmental disorders in depressed children and adolescents
CHILD CARE HEALTH AND DEVELOPMENT,35(5):746-747 2009(Sep.)
Author:D. Sasayama; S. Masutani; J. Imai; Y. Harada; S. Washizuka; N. Amano


子どものこころ診療部における専門医の養成
精神神經學雜誌 = Psychiatria et neurologia Japonica,111(2):194-197 2009(Feb. 25)
Author:原田 謙; 今井 淳子; 篠山 大明; 益谷 幸里; 天野 直二
Abstract:精神神經學雜誌 = Psychiatria et neurologia Japonica


Use of Thiamine in the Treatment of Post-electroconvulsive Therapy Delirium
PHARMACOPSYCHIATRY,42(1):36-37 2009(Jan.)
Author:T. Ogihara; M. Miyashita; M. Kobayashi; D. Sasayama; S. Washizuka; T. Hanihara; N. Amano


Impact of behavioral/developmental disorders comorbid with conduct disorder
PSYCHIATRY AND CLINICAL NEUROSCIENCES,63(6):762-768 2009
Author:Yuzuru Harada; Ayako Hayashida; Shouko Hikita; Junko Imai; Daimei Sasayama; Sari Masutani; Taku Tomita; Kazuhiko Saitoh; Shinsuke Washizuka; Naoji Amano
Abstract:Aims: The aim of the present study was to verify the comorbidity of conduct disorder (CD) and behavioral/developmental disorders in children and adolescents, and to examine the traits of CD comorbid with them. Methods: Subjects were 64 children (60 boys, four girls) who were resident at three institutions for delinquent children or who were conduct-disordered outpatients of a university hospital aged under 18 years. A diagnostic interview was carried out by experienced child psychiatrists and the intelligence score and the Adverse Childhood Experiences score were measured by a licensed psychologist. Results: A total of 57 children were diagnosed as having CD, of whom 26 (45.6%) were diagnosed with comorbid attention-deficit-hyperactivity disorder (ADHD), 12 were diagnosed with comorbid pervasive developmental disorder (PDD, 21,1%), and 19 (33.3%) had no comorbidity of either disorder. Six children (18.8% of CD comorbid with ADHD) met the criteria for both ADHD and PDD. The group with comorbid PDD was significantly younger at onset (F = 6.51, P = 0.003) and included unsocialized type more frequently (KH2 = 6.66, P = 0.036) compared with the other two groups. Conclusions: Clinicians should be aware that not only ADHD but also PDD may be comorbid with CD. Establishment of the correct diagnosis is important because recognizing the presence of PDD will enable us to provide appropriate treatment and guidance, which may improve prognosis.


High-dose paroxetine treatment for an adolescent with obsessive-compulsive disorder comorbid with Asperger's disorder
PSYCHIATRY AND CLINICAL NEUROSCIENCES,63(2):251-251 2009
Author:Daimei Sasayama; Nobuhiro Sugiyama; Junko Imai; Ayako Hayashida; Yuzuru Harada; Naoji Amano


Disease causes less severe lesions in human hippocampus than other parts of brain (vol 62, pg 264, 2008)
PSYCHIATRY AND CLINICAL NEUROSCIENCES,62(5):626-626 2008(Oct.)
Author:M. Kaneko; N. Sugiyama; D. Sasayama; K. Yamaoka; T. Miyakawa; K. Arima; K. Tsuchiya; K. Hasegawa; S. Washizuka; Tokisi Hanihara; N. Amano; S. Yagishita


精神科外来における病名記載の実態に関する検討(第二報):精神分裂病から統合失調症への呼称変更前後の変化
信州医学雑誌,56(3):125-132 2008(Jun.)
Author:高橋徹; 角田美穂; 篠山大明; 天野直二
Abstract:信州医学雑誌


Prion disease causes less severe lesions in human hippocampus than other parts of brain
PSYCHIATRY AND CLINICAL NEUROSCIENCES,62(3):264-270 2008(Jun.)
Author:Kaneko, Minoru; Sugiyama, Nobuhiro; Sasayama, Daimei; Yamaoka, Keiko; Miyakawa, Tomohiro; Arima, Kunimasa; Tsuchiya, Kuniaki; Hasegawa, Kazuko; Washizuka, Shinsuke; Hanihara, Tokisi; Amano, Naoji; Yagishita, Saburo


Prevention of deep vein thrombosis in a patient with delirium tremens.
THE PRIMARY CARE COMPANION TO THE JOURNAL OF CLINICAL PSYCHIATRY,10(1):76-77 2008(Feb.)
Author:Sasayama D; Hosokawa A; Sugiyama N; Kaneko T; Amano N
Abstract:THE PRIMARY CARE COMPANION TO THE JOURNAL OF CLINICAL PSYCHIATRY


Establishing the cut-off point for the Oppositional Defiant Behavior Inventory
PSYCHIATRY AND CLINICAL NEUROSCIENCES,62(1):120-122 2008(Feb.)
Author:Yuzuru Harada; Kazuhiko Saitoh; Junzo Iida; Daimei Sasayama; Ayako Sakai; Junko Imai; Hidemi Iwasaka; Michiko Hirabayashi; Satoru Yamada; Shinichi Hirabayashi; Tokio Uchiyama; Naoji Amano
Abstract:The purpose of the present paper was to make a detailed examination of the cut-off point for the Oppositional Defiant Behavior Inventory (ODBI). The subjects were 56 untreated boys (age 6-15 years), who were diagnosed to have oppositional defiant disorder and who presented between December 2001 and March 2008. Controls were 690 boys with no history of contacting hospitals and no developmental or behavioral disorders at two elementary schools and two junior high schools in a city and its suburbs. It was shown that the level of opposition in boys could be evaluated regardless of the age groups by the ODBI, because there was no significant difference in the ODBI score for the one-way analysis of variance. Based on the sensitivity (88.2%), specificity (90.0%), positive predictive value (75.0%) and negative predictive value (95.7%), a score of 20 points was thus established as a suitable cut-off point to distinguish the children who are eligible for ODD diagnosis from those who are not.


Henoch-Schonlein purpura nephritis complicated by reversible posterior leukoencephalopathy syndrome
CLINICAL RHEUMATOLOGY,26(10):1761-1763 2007(Oct.)
Author:Daimei Sasayama; Yasuhiro Shimojima; Takahisa Gono; Kazuma Kaneko; Masayuki Matsuda; Shu-ichi Ikeda
Abstract:We report a young female patient with Henoch-Schonlein purpura (HSP) nephritis complicated by reversible posterior leukoencephalopathy syndrome (RPLS). The patient suddenly showed generalized seizures and cortical blindness with severe hypertension due to renal insufficiency approximately 1 year after cessation of corticosteroid treatment for HSP nephritis. Magnetic resonance imaging (MRI) demonstrated bilateral abnormal signals mainly in the cerebellum and white matter of the occipital lobe. Clinical symptoms quickly improved in conjunction with disappearance of abnormal signals on brain MRI after starting control of hypertension and continuous hemodiafiltration with steroid pulse therapy and plasmapheresis. RPLS may be caused by vasculitis and also by hemodynamic change due to severe hypertension in HSP, particularly in patients with nephropathy. In such cases intensive treatment should be performed as soon as possible to avoid neurological sequelae.


Massive epistaxis and subconjunctival hemorrhage due to combination of paroxetine and limaprost alfadex: a case report.
THE PRIMARY CARE COMPANION TO THE JOURNAL OF CLINICAL PSYCHIATRY,9(3):240-241 2007(Sep.)
Author:Sugiyama N; Sasayama D; Amano N
Abstract:THE PRIMARY CARE COMPANION TO THE JOURNAL OF CLINICAL PSYCHIATRY


進行性核上性麻痺における周期性昏迷様状態
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society,7(2):87-91 2007(Jun. 01)
Author:篠山 大明; MIYASHITA Mitsuhiro; FUKUDA Takahiro; TAKAHASHI Toru; INUZUKA Shin; WASHIZUKA Shinsuke; HANIHARA Tokiji; AMANO Naoji
Abstract:Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society


Periodic stupor-like states in progressive supranuclear palsy
PSYCHOGERIATRICS,7(2):87-91 2007(Jun.)
Author:Daimei Sasayama; Mitsuhiro Miyashita; Takahiro Fukuda; Toru Takahashi; Shin Inuzuka; Shinsuke Washizuka; Tokiji Hanihara; Naoji Amano
Abstract:Four patients with progressive supranuclear palsy presented with various psychiatric symptoms. Periodic stupor-like states due to fluctuations of consciousness were observed in all four cases. Magnetic resonance imaging showed severe dilatation of the third ventricle suggesting atrophy of the thalami. Neuropathological examination in one of the cases confirmed severe fibrillary gliosis in the intralaminar thalamic nucleus. So far, few studies have focused on periodic stupor-like states observed in progressive supranuclear palsy patients. From our cases and from the literature, we postulate that the lesions in the intralaminar thalamic nuclei may have close relevance to the stupor-like states seen in progressive supranuclear palsy patients.


Remarkable antidepressant augmentation effect of raloxifene, a selective estrogen receptor modulator, in a partial responder to fluvoxamine: A case report
JOURNAL OF CLINICAL PSYCHIATRY,68(4):636-637 2007(Apr.)
Author:Nobuhiro Sugiyama; Daimei Sasayama; Naoji Amano


精神科外来における病名記載の実態に関する検討
信州医学雑誌,54(6):387-393 2006(Dec.)
Author:角田美穂; 高橋徹; 篠山大明; 中村伸治; 岡田八束; 今井淳子; 鷲塚伸介; 原田謙; 野見山哲生; 天野直二
Abstract:信州医学雑誌


MISC
再考「発達障害」 子どものこころの診療室から(第15回)「自然な配慮」とは
教育と医学,69(6):526 2021(Nov.)
Author:篠山 大明


【今日の精神科治療ハンドブック】(第1章)神経発達症群 発達性発話または言語症群
精神科治療学,36(増刊):12 2021(Oct.)
Author:篠山 大明


再考「発達障害」-子どものこころの診療室から(第14回) 誰のための、何のための投薬か
教育と医学,69(5):428 2021(Sep.)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第13回) 薬物療法は必要か
教育と医学,69(4):340 2021(Jul.)
Author:篠山 大明


3年にわたる入院治療を通して心的発達が得られた神経性やせ症の女児の1例と病棟の変化
精神神経学雑誌,123(6):376 2021(Jun.)
Author:公家 里依; 長田 亮太; 田名部 はるか; 篠山 大明; 本田 秀夫; 鷲塚 伸介


精神科病棟における子どもを対象とした入院集団精神療法の取り組み(第2報) 自閉スペクトラム症思春期女子症例にみられた変化
精神神経学雑誌,123(6):375 2021(Jun.)
Author:牧田 みずほ; 公家 里依; 児島 佳代子; 宮澤 友真; 本田 秀夫; 篠山 大明; 鷲塚 伸介


自閉スペクトラム症を背景とする神経性やせ症の男子例
日本小児科学会雑誌,125(5):831 2021(May)
Author:荒井 萌子; 夏目 岳典; 倉沢 伸吾; 原 洋祐; 福山 哲広; 新美 妙美; 篠山 大明


再考「発達障害」 子どものこころの診療室から(第12回) 発達障害を「カモフラージュ」する人
教育と医学,69(3):246 2021(May)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第11回) 「発達障害は遺伝しますか?」
教育と医学,69(2):150 2021(Mar.)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第10回) 「褒めること」の持つ意味
教育と医学,69(1):54 2021(Jan.)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第9回)「やればできる、でも難しい」こと
教育と医学,68(6):532 2020(Nov.)
Author:篠山 大明


【児童・青年期の精神疾患治療ハンドブック】コミュニケーション症群 コミュニケーション症群
精神科治療学,35(増刊):148 2020(Oct.)
Author:篠山 大明


スマートフォンの使用、睡眠、心理的ストレス、注意機能の関連
精神神経学雑誌,(2020特別号):S566 2020(Sep.)
Author:篠山 大明; 竹森 由佳; 小田切 みのり; 樋田 優希代; 杉山 暢宏; 山口 昌樹; 鷲塚 伸介; 本田 秀夫


再考「発達障害」 子どものこころの診療室から(第8回) 良いコミュニケーションを育てるために大切なこと
教育と医学,68(5):438 2020(Sep.)
Author:篠山 大明


精神科病棟における子どもを対象とした入院集団精神療法の取り組み(第1報)
精神神経学雑誌,122(8):626 2020(Aug.)
Author:青木 宗佑; 公家 里依; 倉橋 佳那; 本田 秀夫; 篠山 大明; 鷲塚 伸介


再考「発達障害」 子どものこころの診療室から(第7回) 発達障害とコミュニケーションスタイル
教育と医学,68(4):344 2020(Jul.)
Author:篠山 大明


当院小児科における神経性やせ症患者の入院管理
脳と発達,52(3):203 2020(May)
Author:荒井 萌子; 夏目 岳典; 柳沢 俊光; 公家 里衣; 新美 妙美; 篠山 大明; 福山 哲広


再考「発達障害」 子どものこころの診療室から(第6回) 「診断を活かす」ということ
教育と医学,68(3):252 2020(May)
Author:篠山 大明


【児童青年精神医学をどう学ぶのか?大学で、病院で、自分で】長野県発達障がい診療人材育成事業における医師育成カリキュラム
児童青年精神医学とその近接領域,61(2):82 2020(Apr.)
Author:篠山 大明
Abstract:近年の発達障害診療ニーズの増加を受け、長野県では、発達障害診療の人材を育成する県の事業を受託する形で、2018年4月に信州大学医学部子どものこころの発達医学教室が開設された。当教室が担う役割の一つが、発達障害の診療ができる医師の育成を目的とする「長野県発達障がい診療医・専門医育成カリキュラム」の遂行である。本カリキュラムは全12回の講義、外来陪席実習、多職種の事例検討会での事例提示、スーパービジョンを含んでいる。長野県発達障がい診療医については上記の履修によって、また、同専門医については上記履修に加えて所定の臨床経験を積むことによって、県に認定の申請をすることができる。5年間で診療医25名、専門医5名程度の育成を目指して開始したカリキュラムであったが、初年度の2018年度で、すでに33名が診療医コース、9名が専門医コースに登録を行い受講を開始した。想定を上回る受講人数からは、多くの医師が発達障害診療について系統立てて学ぶ機会を求めていたことが窺える。本カリキュラムによって発達障害のプライマリー診療を行える医師が増加し、県内の発達障害診療体制の整備がすすむことが期待される。(著者抄録)


再考「発達障害」 子どものこころの診療室から(第5回)発達障害を「治す」とは
教育と医学,68(2):158 2020(Mar.)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第4回) 自閉スペクトラム症の歴史 スペクトラム概念の導入
教育と医学,68(1):62 2020(Jan.)
Author:篠山 大明


自閉スペクトラム症および注意欠如・多動症の子どもと保護者に対する効率的なアンガーマネージメントプログラムの開発
日本児童青年精神医学会総会抄録集,60回:P19 2019(Dec.)
Author:倉橋 佳那; 児島 佳代子; 青木 宗佑; 樋端 佑樹; 公家 里依; 篠山 大明; 本田 秀夫


児童・思春期の神経性やせ症を対象とした家族で行う認知機能改善療法の実施可能性の検討
日本児童青年精神医学会総会抄録集,60回:O5 2019(Dec.)
Author:公家 里依; 倉橋 佳那; 青木 宗佑; 篠山 大明; 本田 秀夫


脳と心は利己的免疫システムに支配されるのか? 精神疾患と神経炎症
臨床神経学,59(Suppl.):S174 2019(Nov.)
Author:篠山 大明


児童精神医学と脳科学 神経発達症の生物学的研究
児童青年精神医学とその近接領域,60(5):602 2019(Nov.)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第3回) 自閉スペクトラム症の歴史 想定される原因の変遷
教育と医学,67(9):744 2019(Nov.)
Author:篠山 大明


【神経発達症の最新トピックス〜診療・支援・社会】自閉スペクトラム症とADHDの現在 自閉スペクトラム症概念の普及は児童思春期精神科診療をどう変えたか
臨床精神医学,48(10):1137 2019(Oct.)
Author:篠山 大明


再考「発達障害」 子どものこころの診療室から(第2回) ADHDの歴史と変遷
教育と医学,67(8):654 2019(Sep.)
Author:篠山 大明


長野県内の小児科医と精神科医を対象とした発達障害診療の実態、および連携と移行に関するアンケート調査
精神神経学雑誌,121(7):575 2019(Jul.)
Author:樋端 佑樹; 新美 妙美; 本田 秀夫; 公家 里依; 篠山 大明; 鷲塚 伸介; 稲葉 雄二


再考「発達障害」 子どものこころの診療室から(第1回) 発達障害は「ブーム」なのか
教育と医学,67(7):566 2019(Jul.)
Author:篠山 大明


うつ病のComorbidity ADHDとうつ病
Depression Journal,6(3):86 2018(Dec.)
Author:篠山 大明


信州大学医学部附属病院における精神科リエゾンチーム活動の認知度と課題
総合病院精神医学,30(Suppl.):S 2018(Nov.)
Author:中村 敏範; 戸谷 理沙; 濱本 緑; 白石 健; 篠山 大明; 本田 秀夫; 鷲塚 伸介


長野県内の小児科医および精神科医を対象とした発達障害診療の実態、診療連携と移行に関するアンケート調査
日本児童青年精神医学会総会抄録集,59回:P7 2018(Oct.)
Author:樋端 佑樹; 篠山 大明; 新美 妙美; 公家 里依; 児島 佳代子; 本田 秀夫; 倉橋 佳那


児童精神医学と脳科学 児童精神医学と脳科学 神経発達症の生物学的研究
日本児童青年精神医学会総会抄録集,59回:S11 2018(Oct.)
Author:篠山 大明


北アルプス医療センターあづみ病院におけるアルコール依存症入院患者の経過
日本アルコール・薬物医学会雑誌,53(4):190 2018(Aug.)
Author:中村 敏範; 雨宮 光太郎; 篠山 大明; 高橋 徹; 村田 志保; 鷲塚 伸介


ストレス脆弱性についての表現型と末梢血トランスクリプトームの統合解析
臨床薬理の進歩,(39):140 2018(Jun.)
Author:堀 弘明; 中村 誠二; 吉田 冬子; 寺石 俊也; 篠山 大明; 太田 深秀; 服部 功太郎; 金 吉晴; 樋口 輝彦; 功刀 浩


ストレス脆弱性についての表現型と末梢血トランスクリプトームの統合解析
臨床薬理の進歩,(39):140 2018(Jun.)
Author:堀 弘明; 中村 誠二; 吉田 冬子; 寺石 俊也; 篠山 大明; 太田 深秀; 服部 功太郎; 金 吉晴; 樋口 輝彦; 功刀 浩
Abstract:ストレス脆弱性の個別性・連続性を焦点とし、その表現型と分子基盤を統合的に検討することを目的とした。一般人口から募集した健常成人を対象に、各個人の心理特性プロフィールに基づいて行ったストレス脆弱性分類と、末梢血RNAを用いて測定したトランスクリプトームの関連について検討した。ストレスからの回復力を持つ「Resilient」群、ストレスの影響を受けにくい「Resistant」群、ストレス脆弱性を有する「Vulnerable」群20名ずつ合計60名を対象に保存RNA検体をマイクロアレイ解析に供した。さらに、うつ病患者106名、健常者60名を対象に、重要性が示唆される遺伝子の発現変動を調べた。6個のリボソーム遺伝子であるRPL17、RPL21、RPL34、RPL36AL、RPL39、RPS27の発現レベルを比較したところ、発現レベルの平均値はうつ病患者において最も高く、健常対照者において最も低く、寛解うつ病患者はその中間であった。qPCRによるreplication実験において、RPL17、RPL34とも、うつ病患者で有意な発現亢進が再現された。


出生コホートの悉皆調査で幼児期に把握した自閉スペクトラム症(ASD)の成人期までの長期追跡
先進医薬研究振興財団研究成果報告集,2017年度:64 2018(Mar.)
Author:本田 秀夫; 岩佐 光章; 清水 康夫; 原 郁子; 今井 美保; 篠山 大明


【診断と治療のABC[130]発達障害】(第1章)概念と定義 ASDの概念
最新医学,別冊(発達障害):22 2018(Jan.)
Author:篠山 大明
Abstract:自閉症の概念は、歴史と共に変遷を遂げている。スペクトラム概念が導入された現在も、自閉スペクトラム症(ASD)は、社会的コミュニケーションや限定された反復的な行動様式など、行動特性のみによって定義された概念である。その行動特性の背景には生物学的基盤の存在が想定されているが、詳しい機序は解明されていない。臨床像は多様で、カテゴライズすることが困難な概念であり、スペクトラムとしての理解が定着している。(著者抄録)


【大人の発達障害】大人の発達障害と双極性障害との関係
精神科治療学,32(12):1597 2017(Dec.)
Author:篠山 大明
Abstract:発達障害と双極性障害はまったく異なる診断概念であるが、臨床場面では両者の鑑別診断が困難な症例や、両者を併存する症例に遭遇することがある。いずれも病態生理がほとんど解明されていない障害であり、診断概念自体も時代とともに変遷している。今までの研究では、発達障害と双極性障害は併存する率が高いことが示されているが、診断概念を踏まえると、併存状態とはベースに発達障害がある人に双極性障害が発症したことを意味する。併存状態が生じやすい原因としては、診断概念の共通点やオーバーラップの影響、共通する病因の存在などが考えられる。さらに、発達障害の存在自体が双極性障害の発症を引き起こす原因となる可能性もある。診断概念や病因仮説をもとに、発達障害と双極性障害の関係および両者が併存する率が高い理由について考察する。(著者抄録)


神経発達症に関連する乳幼児健康診査項目の検討 長野県岡谷市コホートにおける解析結果
日本児童青年精神医学会総会抄録集,58回:122 2017(Oct.)
Author:篠山 大明; 倉橋 佳那; 小田 佳代子; 平林 恵美; 金子 和可子; 野見山 哲生; 小泉 典章; 本田 秀夫


脳脊髄液中D-セリン濃度とうつ病重症度の関連
日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集,39回・47回:170 2017(Sep.)
Author:石渡 小百合; 服部 功太郎; 篠山 大明; 寺石 俊也; 宮川 友子; 横田 悠季; 松村 亮; 西川 徹; 功刀 浩


精神疾患の脳脊髄液における補体C5の亢進
日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集,39回・47回:169 2017(Sep.)
Author:石井 敬; 服部 功太郎; 宮川 友子; 篠山 大明; 秀瀬 真輔; 太田 深秀; 横田 悠季; 松村 亮; 野田 隆政; 吉田 寿美子; 後藤 雄一; 功刀 浩


発達障害に併存する気分変動の評価と治療 (特集 発達障害に対する薬物療法の新展開)
臨床精神薬理,20(6):655 2017(Jun.)
Author:篠山 大明
Abstract:近年、発達障害を基盤にした気分変動が臨床的に注目されている。発達障害に併存する気分変動には、発達障害の特性を踏まえた治療戦略が必要である。本稿では、発達障害に気分変動が発症する要因について解説し、症状を評価する上での注意点や治療法について考察する。発達障害と気分障害の併存例には多種多様な要因によってさまざまな状態を呈するケースが含まれるため、画一的な対応では症状の改善は見込めない。現存するエビデンスを参考にしつつ、症例ごとに気分変動が生じた原因を探索して問題点を整理し、試行錯誤しながら治療目標に向けて最適な方法を見つけていく姿勢が臨床家に求められる。(著者抄録)


脳動静脈奇形術後の高次脳機能障害を背景とした学校不適応、行動障害のため入院を要した1例
精神神経学雑誌,(2017特別号):S632 2017(Jun.)
Author:鵜澤 正寛; 樋端 佑樹; 篠山 大明; 本田 秀夫


電気けいれん療法の発作に対するベンゾジアゼピン投与の影響
精神神経学雑誌,(2017特別号):S616 2017(Jun.)
Author:大屋 大; 飯沢 美文; 鵜澤 正寛; 高橋 和史; 荻原 朋美; 篠山 大明; 鷲塚 伸介


老年期におけるエストロゲンβ受容体内因性リガンドの血清濃度の性差について
精神神経学雑誌,(2017特別号):S300 2017(Jun.)
Author:小林 美雪; 杉山 暢宏; 篠山 大明; 笹本 英彦; 宮代 好通; 有馬 邦正; 鷲塚 伸介


統合失調症およびうつ病患者における血漿・脳脊髄液中G72タンパク量の変化
日本神経精神薬理学雑誌,37(3):101 2017(Jun.)
Author:石渡 小百合; 服部 功太郎; 篠山 大明; 寺石 俊也; 宮川 友子; 横田 悠季; 松村 亮; 西川 徹; 功刀 浩


母子保健情報を活用した子どもの精神健康問題の早期発見と早期支援 岡谷市における悉皆的コホート研究
精神神経学雑誌,119(5):360 2017(May)
Author:篠山 大明; 小泉 典章; 八木 芳雄; 金子 和可子; 工藤 哲也; 野見山 哲生; 小田 佳代子; 倉橋 佳那; 本田 秀夫


【思春期以降のADHD】ADHDの異種性
教育と医学,65(1):4 2017(Jan.)
Author:篠山 大明


精神医学のフロンティア メランコリー型の特徴を伴う大うつ病性障害と非定型の特徴を伴う大うつ病性障害の白質障害の違い
精神神経学雑誌 = Psychiatria et neurologia Japonica,119(5):295 2017
Author:太田 深秀; 野田 隆政; 佐藤 典子; 服部 功太郎; 堀 弘明; 篠山 大明; 寺石 俊也; 長島 杏奈; 大部 聡子; 樋口 輝彦; 功刀 浩
Abstract:DSM-IVでは大うつ病性障害(MDD)に下位分類を特定することがある.MDDでは下位分類ごとに薬物療法への効果などが異なることから下位分類の特定をすることは非常に重要である.これまでにメランコリー型の特徴を伴う大うつ病性障害(mMDD)と非定型の特徴を伴う大うつ病性障害(aMDD)における局所脳形態変化の差は明らかとされていない.今回われわれは拡散強調画像を用いてこの2疾患の障害の差を検討した.mMDD患者21名,aMDD患者24名と年齢性別をあわせた健常者37名を対象に拡散強調画像を撮影した.拡散強調画像で得られるfractional anisotropy値とmean diffusivity値を対象として診断ごとの脳形態の差異を検討した.mMDDおよびaMDD患者はそれぞれ健常者と比較して脳梁,下前頭後頭束,左上縦束部分に障害が認められた.しかしmMDDとaMDDの間には有意な差は認められなかった.MDD患者では健常者と比較して大脳形態変化が存在することが明らかとなったが,MDDの下位分類ごとの比較では明らかな違いが認められなかった.反復するうつ病エピソード中の臨床症状は異なりうるため,これまでメランコリー型で経過していた症例が突如非定型なうつ病エピソードを呈することもある.今回の横断的な下位分類の特定では,下位分類ごとの局所脳形態変化の違いを検出することはできなかった.(著者抄録)


Involvement of hypothalamic-adrenal-pituitary axis in the mechanism of transcriptome-wide identified differentially expressed genes for depression
EUROPEAN NEUROPSYCHOPHARMACOLOGY,26:S199 2016(Oct.)
Author:H. Hori; D. Sasayama; T. Teraishi; N. Yamamoto; S. Nakamura; M. Ota; K. Hattori; Y. Kim; T. Higuchi; H. Kunugi


Increased cerebrospinal fluid fibrinogen levels in major depressive disorder replicated in a larger sample set
EUROPEAN NEUROPSYCHOPHARMACOLOGY,26:S403 2016(Oct.)
Author:K. Hattori; D. Sasayama; S. Hidese; T. Miyakawa; M. Ota; H. Hori; S. Yoshida; Y. Goto; H. Kunugi


双極性障害患者の血清中ラモトリギン濃度に影響を及ぼす因子の検討(Factors influencing serum levels of lamotrigine in patients with bipolar disorder)
日本神経精神薬理学会年会プログラム・抄録集,46回:215 2016(Jul.)
Author:高橋 和史; 篠山 大明; 荻原 朋美; 犬塚 伸; 杉山 暢宏; 鷲塚 伸介


大うつ病性障害における血漿中アミノ酸濃度の変化
日本神経精神薬理学会年会プログラム・抄録集,46回:214 2016(Jul.)
Author:小川 眞太朗; 服部 功太郎; 古賀 賀恵; 篠山 大明; 太田 深秀; 堀 弘明; 寺石 俊也; 吉田 寿美子; 野田 隆政; 樋口 輝彦; 功刀 浩


夜驚症および睡眠時遊行症に対してラメルテオンが有効であった一例(Effective treatment of night terrors and sleepwalking with ramelteon: a case report)
日本神経精神薬理学会年会プログラム・抄録集,46回:159 2016(Jul.)
Author:篠山 大明; 鷲塚 伸介; 本田 秀夫


【精神疾患の予防と早期治療アップデート】発達障害の併存症(Comorbidity)への早期介入
精神医学,58(7):623 2016(Jul.)
Author:樋端 佑樹; 篠山 大明; 本田 秀夫


家族状況が衝動統制に大きく影響した成人期注意欠如・多動症の一例
精神神経学雑誌,(2016特別号):S611 2016(Jun.)
Author:鵜澤 正寛; 萩原 徹也; 多田 はるか; 篠山 大明; 荻原 朋美; 高橋 徹; 鷲塚 伸介


【臨床現場から見た精神疾患の変貌】自閉スペクトラム症は増えているのか
臨床精神医学,45(1):29 2016(Jan.)
Author:篠山 大明; 本田 秀夫


精神疾患脳脊髄液バイオリソースの構築とバイオマーカーの探索
日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集,37回・45回:213 2015(Sep.)
Author:服部 功太郎; 篠山 大明; 吉田 寿美子; 功刀 浩


母子保健情報を活用した子どもの精神健康問題の早期発見と早期支援 : 長野県の自治体における悉皆的コホート研究
研究助成論文集,(51):65 2015
Author:篠山 大明; 小泉 典章; 八木 芳雄; 金子 和可子; 工藤 哲也; 野見山 哲生; 小田 佳代子; 倉橋 佳那


【自閉症】自閉症序論
神経内科,81(4):369 2014(Oct.)
Author:篠山 大明; 本田 秀夫


小児・思春期精神医学 自閉症スペクトラム障害におけるカタトニア
精神科,25(1):84 2014(Jul.)
Author:由井 寿美江; 篠山 大明; 原田 謙


児童期発症の双極性障害が疑われる症例
精神神経学雑誌,116(5):416 2014(May)
Author:篠山 大明; 倉橋 佳那; 原田 謙; 天野 直二


うつ病における血漿中遊離アミノ酸濃度の変化
日本栄養・食糧学会大会講演要旨集,68回:168 2014(Apr.)
Author:小川 眞太朗; 山本 宣子; 堀 弘明; 寺石 俊也; 太田 深秀; 服部 功太郎; 篠山 大明; 松尾 淳子; 長島 杏那; 木下 裕紀子; 石田 一希; 古賀 賀恵; 樋口 輝彦; 功刀 浩


精神医学のフロンティア MRIによる女性統合失調症患者と女性健常群との判別分析
精神神経学雑誌,115(12):1171 2013(Dec.)
Author:太田 深秀; 佐藤 典子; 石川 正憲; 堀 弘明; 篠山 大明; 服部 功太郎; 寺石 俊也; 大部 聡子; 中田 安弘; 根本 清貴; 守口 善也; 橋本 亮太; 功刀 浩
Abstract:統合失調症に特異的な局所脳形態の変化様式に焦点を当てた統合失調症と健常者の判別分析を行った。第1段階としてDSM-IVの診断基準に合致した女性統合失調症患者38名と健常女性135名の脳画像の情報から判別関数を作成した。第2段階として女性統合失調症患者23名と健常女性23名の画像情報を判別関数に代入し同様の判別率が得られるかについて検討した。ステップワイズ法により、右島、内側前頭葉、右頭頂葉、第3脳室の容量を判別分析に用いることとなった。判別係数はそれぞれ-8.7、-10.3、19.7、4.9であり、定数は1.2であった。第1被験者群を対象とした判別分析では、統合失調者群を0.76の正解率で、健常群を0.72の正解率で判別した。第2被験者群の右島、内側前頭葉、右頭頂葉、第3脳室の容量をこの判別関数に代入した結果、統合失調者群を正解率0.74で、健常群を0.70の正解率で判別した。局所脳形態の変化を複数組み合わせて解析することで女性統合失調症患者を高い精度で判別可能なことが示唆された。


ベンゾジアゼピン系薬剤、ベンゾジアゼピン様薬剤、定型抗精神病薬による統合失調症患者の手指巧緻性の低下
日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集,23回・43回:219 2013(Oct.)
Author:篠山 大明; 堀 弘明; 寺石 俊也; 服部 功太郎; 太田 深秀; 松尾 淳子; 木下 裕紀子; 岡崎 光俊; 有馬 邦正; 天野 直二; 樋口 輝彦; 功刀 浩


NIRSを用いた老年期うつ病とアルツハイマー病の大脳皮質賦活反応性についての検討
Dementia Japan,27(4):529 2013(Oct.)
Author:鬼頭 恆; 両川 晃子; 木下 善弘; 篠山 大明; 杉山 暢宏; 荻原 朋美; 萩原 徹也; 埴原 秋児; 鷲塚 伸介; 天野 直二


大うつ病性障害におけるパーソナリティはコルチゾール反応性を予測する デキサメタゾン/CRHテストによる検討
日本神経精神薬理学雑誌,33(2):61 2013(Apr.)
Author:堀 弘明; 寺石 俊也; 篠山 大明; 服部 功太郎; 橋倉 都; 樋口 輝彦; 功刀 浩
Abstract:大うつ病性障害におけるパーソナリティと、うつ病の診断ツールであるデキサメタゾン(DEX)/corticotropin-releasing hormone(CRH)テストに対するコルチゾールの反応性について、コルチゾールの過剰抑制に焦点を当て、外来うつ病患者87名(男性41名、女性46名。21〜69歳、平均年齢40.1±10.7歳)を対象に検討、報告した。その結果、1)コルチゾール非抑制者に比べ、過剰抑制者では協調性が有意に低く、2)高い報酬依存と低い協調性の組み合わせが過剰抑制を有意に予測することが分かった。


脳脊髄液を用いた統合失調症バイオマーカーの開発
精神薬療研究年報,(45):57 2013(Mar.)
Author:服部 功太郎; 篠山 大明; 功刀 浩


小児・思春期精神医学 自閉症スペクトラム障害の原因 どこまで解明されたのか
精神科,21(5):602 2012(Nov.)
Author:篠山 大明; 原田 謙


安定同位体を用いた呼気ガス検査の精神疾患における有用性の検討
日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集,22回・42回:201 2012(Oct.)
Author:寺石 俊也; 尾関 祐二; 堀 弘明; 篠山 大明; 千葉 秀一; 山本 宜子; 田中 治子; 飯嶋 良味; 松尾 淳子; 川本 由実子; 木下 裕紀子; 服部 功太郎; 太田 深秀; 梶原 正宏; 寺田 純雄; 樋口 輝彦; 功刀 浩


SCHIZOTYPY AND GENETIC LOADING FOR SCHIZOPHRENIA IMPACT UPON NEUROPSYCHOLOGICAL STATUS IN BIPOLAR II AND UNIPOLAR MAJOR DEPRESSIVE DISORDERS
SCHIZOPHRENIA RESEARCH,136:S330 2012(Apr.)
Author:Hiroaki Hori; Junko Matsuo; Toshiya Teraishi; Daimei Sasayama; Yumiko Kawamoto; Yukiko Kinoshita; Kotaro Hattori; Miyako Hashikura; Teruhiko Higuchi; Hiroshi Kunugi


【脳の機能と統合失調症-新たな診断と治療への展望-II】脳脊髄液(CSF)からみた統合失調症のモノアミン代謝産物の解析
精神科治療学,26(12):1557 2011(Dec.)
Author:服部 功太郎; 寺石 俊也; 篠山 大明; 功刀 浩
Abstract:1970年代以降、統合失調症のドーパミン仮説を検討するために、脳脊髄液(CSF)を用いたモノアミン代謝産物の解析が行われてきた。薬剤フリーの統合失調症CSFを用いた研究において、ドーパミン代謝産物であるホモバニリン酸(HVA)は、健常対照群と同等という報告が多く、減少しているとする報告も散見された。このことから統合失調症の脳において、少なくともドーパミン放出量は増加していないことが示唆された。また、薬剤フリーの統合失調症患者に抗精神病薬の投与を数週間行うと、CSF中のHVAは投与前に比べて上昇し、HVA上昇と陽性症状の改善とが相関するという報告も多かった。このようにCSFモノアミン代謝の解析は統合失調症分子病態の解明には貢献するが、臨床マーカーとしての有用性は、現状では限られる。しかし、蛋白質解析技術の進歩に従い、近年CSFの脳神経疾患のバイオリソースとしての価値が再評価されており、統合失調症バイオマーカーの開発に役立つことが期待される。(著者抄録)


統合失調症患者における血中サイトカイン濃度およびサイトカイン関連遺伝子のSNP解析(Analysis of plasma cytokine level and cytokine-related genetic polymorphism in schizophrenia)
神経化学,49(2-3):497 2010(Aug.)
Author:若林 千里; 篠山 大明; 功刀 浩


統合失調症患者とうつ病患者の認知機能に関する日本語版統合失調症認知機能簡易評価尺度(BACS-J)による検討
精神神経学雑誌,(2010特別):S 2010(May)
Author:松尾 淳子; 木下 裕紀子; 川本 由実子; 須藤 志保; 橋倉 都; 堀 弘明; 寺石 俊也; 篠山 大明; 服部 功太郎; 尾関 祐二; 有馬 邦正; 石川 正憲; 岡本 長久; 樋口 輝彦; 兼田 康宏; 功刀 浩


統合失調症患者の運動機能障害に関するペグボードと握力検査による検討
精神神経学雑誌,(2010特別):S 2010(May)
Author:川本 由実子; 松尾 淳子; 橋倉 都; 木下 裕紀子; 須藤 志保; 堀 弘明; 寺石 俊也; 篠山 大明; 服部 功太郎; 尾関 祐二; 有馬 邦正; 石川 正憲; 岡本 長久; 樋口 輝彦; 功刀 浩


反抗的、挑戦的、攻撃的な行動がみられるADHD児に対する薬物療法 (ADHD薬物療法の新時代--コンサータとストラテラ) -- (薬物療法が第一選択とされる昨今のADHD対策)
現代のエスプリ,(513):50 2010(Apr.)
Author:篠山 大明


10年前から認知症が疑われてきた薬剤性せん妄の1例
精神神経学雑誌,112(4):423 2010(Apr.)
Author:山本 孝; 南風原 泰; 松本 武典; 篠山 大明; 松澤 冨男; 小宮山 徳太郎


Imaginary Companionを持つアスペルガー症候群の一例
精神神経学雑誌,112(2):182 2010(Feb.)
Author:益谷 幸里; 疋田 祥子; 篠山 大明; 今井 淳子; 原田 謙; 天野 直二; 萩原 徹也


子どもの抑うつ状態に対する薬物療法の現状
精神神経学雑誌,112(1):82 2010(Jan.)
Author:篠山 大明; 益谷 幸里; 今井 淳子; 疋田 祥子; 堂籠 やよい; 原田 謙; 天野 直二


行動制止を伴ったアスペルガー男児の一例
日本児童青年精神医学会総会抄録集,50回:170 2009(Sep.)
Author:今井 淳子; 篠山 大明; 疋田 祥子; 原田 謙


【発達障害のリハビリテーション】発達障害の薬物治療
MEDICAL REHABILITATION,(103):18 2009(Mar.)
Author:篠山 大明; 原田 謙
Abstract:発達障害に対する薬物治療としてまだ確立されたものはないが、補助的に薬物療法を並行して行うことで様々な問題や合併症を軽くして、より効果的な療育を行うことができる。用いられる薬剤には、抗精神病薬、抗うつ薬、抗不安薬・睡眠導入薬、中枢神経刺激薬などがある。感情のコントロールが困難な場合などには療育の補助として用い、うつ状態や強迫症状などが併存する場合は精神症状の治療として用いる。また、睡眠障害やチックなどを認める場合も、生活の質を改善するために用いることがある。薬物療法を行う際は、必ず何を目的としているのかを理解することが重要である。活動場面における情報を総合して効果を評価しながら薬物を使用し、より良い療育を目指すことが求められている。(著者抄録)


少量のフルボキサミンで治療中、ラロキシフェンを併用したところ奏功した遷延性うつ病の1例
精神神経学雑誌,110(10):990 2008(Oct.)
Author:篠山 大明; 杉山 暢宏; 天野 直二


【AD/HDに対する薬物療法のエビデンス】AD/HDに併存する破壊的行動障害に対する薬物療法のエビデンス
臨床精神薬理,11(4):643 2008(Apr.)
Author:篠山 大明; 原田 譲
Abstract:破壊的行動障害(DBD)は反抗的、挑戦的行動によって特徴づけられる障害であり、注意欠陥/多動性障害(AD/HD)と併存することが多い。AD/HDに併存するDBDに対する治療法はまだ確立されていないが、さまざまな研究で薬物療法が有効であるというエビデンスが示されている。AD/HD治療薬であるmethylphenidateは、DBD症状の改善にも有効であることが多くの研究で示されているため、現時点では最も推奨されている薬物である。また、攻撃性に対しては抗精神病薬、atomoxetineなどの有効性が報告されている。DBDでみられる反抗的行動や攻撃性は、生物学的要因と環境的要因が複雑に影響しあって発現しているため、個々の症例に合わせて治療法を選択することが重要であり、薬物療法の際には心理社会的介入も併用して行うことが推奨されている。(著者抄録)


【高齢者医療の危機管理】高齢者の精神障害と医療事故
Geriatric Medicine,46(2):171 2008(Feb.)
Author:篠山 大明; 天野 直二


【非定型抗精神病薬と老年期精神疾患】非定型抗精神病薬の特徴
老年精神医学雑誌,18(7):707 2007(Jul.)
Author:篠山 大明; 天野 直二
Abstract:従来の定型抗精神病薬の主な標的であったドーパミンD2受容体に加え、セロトニン5-HT2受容体への拮抗作用をあわせもつ非定型抗精神病薬が広く使用されるようになってきた。セロトニン5-HT2受容体の拮抗薬にはドーパミンD2受容体遮断により生じる錐体外路症状を軽減する効果や統合失調症の陰性症状を改善させる作用などがある。さまざまな薬理学的プロフィールをもつ非定型抗精神病薬の特徴を生かすことで、副作用が問題となりやすい高齢者でも比較的安全に治療を行うことが可能となる。(著者抄録)


【児童思春期精神医学の最近の進歩】子どものこころの障害 AD/HDの症状の変遷と治療
臨床精神医学,36(5):597 2007(May)
Author:篠山 大明; 原田 謙


【症状性(器質性)精神障害の治療ガイドライン】第4章 脳に限定した特発性の疾病過程が認知症をもたらす病態 2)皮質下性 4)進行性核上性麻痺
精神科治療学,21(増刊):321 2006(Oct.)
Author:篠山 大明


経過中に脳症を認めたアレルギー性紫斑病の1例
臨床神経学,45(7):545 2005(Jul.)
Author:篠山 大明; 下島 恭弘; 五野 貴久; 兼子 一真; 池田 修一

研究費
科学研究費補助金(研究代表者)
2021 - 2023 , 母子保健情報の活用による精神健康問題の早期発見のための悉皆的コホート研究 , 基盤C
2017 - 2020 , 児童精神科領域における臨床応用可能な唾液ストレスマーカーの開発
2015 - 2016 , 実用的な診断および薬物治療反応性評価を可能とするADHDの新規バイオマーカー探索
2013 - 2014 , 子どものうつ症状と自閉症スペクトラムにおけるサイトカインの役割

科学研究費補助金(研究分担者)
2020 - 2021 , 特別児童扶養手当 (精神の障害) の認定事務の適正化に向けた調査研究
2018 - 2019 , 発達障害の原因、疫学に関する情報のデータベース構築のための研究
2017 - 2018 , 発達障害児者等の地域特性に応じた支援ニーズとサービス利用の実態の把握と支援内容に関する研究

その他公的資金
2015 - 2018 , 母子保健情報を活用した子どもの精神健康問題の早期発見と早期支援-諏訪圏域の自治体における悉皆的コホート研究
2012 - 2014 , 自閉症スペクトラム障害の下位分類の提唱
2012 - 2012 , 自閉症スペクトラム障害の神経心理学的特性とバイオマーカー