大渓 俊幸

自閉症スペクトラム症に対する認知行動療法(CBT)の効果予測指標についての予備的研究として、ASDである大学生17名(男性10名、女性7名)と定型発達者17名(男性10名、女性7名)を対象に、CBTや通常の治療(TAU)による脳機能の変化として、流暢性課題(VFT)施行中の脳活動を近赤外分光法により測定するとともに、状態評価として、全体的評定尺度(GAF)、社会的適応自己評価尺度などを用いた測定を行った。その結果、ASD群と定型発達群の比較では、ASD群では全体的な機能や社会適応が低下して支障をきたしており、認知機能の柔軟性を評価するVFT施行時にみられる脳活動が小さかった。また、ASDの学生でみられるVFT施行時の脳活動の大きさと、CBTとTAUの併用によりもたらされるGAFスコアの改善の間には正の相関がみられたことから、VFT施行時の脳活動の大きさが、TAUに加えてCBTを行うことによりもたらされる治療効果の予測指標となる可能性が示唆された。

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5 years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal–retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition. (C) 2016 Published by Elsevier Ltd on behalf of IBRO.

Background: The lowering of the age of onset and chronicity have been key problems related to eating disorders (EDs). As the proportion of teens in the estimated onset ages has increased, it has become important to detect students with EDs and to clarify how they can be supported. Though epidemiological surveys of Yogo teachers (school nurse/health science teachers) have been conducted to inquire about the number of such students, none of these were done according to ED type based on DSM-5. Thus, we conducted a wide area survey in Japan with the goal of proposing a better framework of support for Yogo teachers in their efforts to care for students with EDs. Methods: A questionnaire survey organized by ED type (based on DSM-5) was administered to Yogo teachers working at elementary/junior high/senior high/special needs schools in four prefectures of Japan in 2015, and 1,886 responses were obtained. Based on the results, the encounter rates (the proportion of Yogo teachers who had encountered a student with an ED) were calculated, and factors that could affect the rates were examined by logistic regression analysis. Results: The order of the encounter rates of the ED types was as follows: Anorexia Nervosa (AN) > Bulimia Nervosa (BN) > Avoidant/Restrictive Food Intake Disorder (ARFID) > Binge Eating Disorder (BED) > Others. The factors significantly affecting the rates were "location, school type, number of students, experience years, and AN knowledge" for AN, "school type, experience years, and BN knowledge" for BN, "school type, experience years, and BED knowledge" for BED, "location, experience years, and ARFID knowledge" for ARFID, and "school type, experience years, and Others knowledge" for Others. Conclusions: Because the encounter rate of AN was the highest, providing support for AN would be the most effective. Moreover, one factor that affected the encounter rate of all ED types was ED knowledge. In addition to this, senior high schools had the highest encounter rates for AN, BN and BED, and special needs schools had the highest rates for Others. These findings imply that, in order to detect and support ED students at an early stage, it is necessary to offer knowledge of the most prevalent ED types to Yogo teachers at the corresponding school type.

Background: Many studies have focused on the decreasing age of onset of eating disorders (EDs). Because school-age children with EDs are likely to suffer worse physical effects than adults, early detection and appropriate support are important. The cooperation of Yogo teachers is essential in helping these students to find appropriate care. To assist Yogo teachers, it is helpful to clarify the encounter rates (the proportion of Yogo teachers who have encountered ED students) and kinds of requested support (which Yogo teachers felt necessary to support ED students). There are no studies that have surveyed the prevalence rates of ED children by ED type as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), nor were we able to find any quantitative study surveying the kinds of support Yogo teachers feel helpful to support ED students. Methods: A questionnaire survey was administered to 655 Yogo teachers working at elementary/junior high/senior high/special needs schools in Chiba Prefecture. The questionnaire asked if the respondents had encountered students with each of the ED types described in DSM-5 (anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), avoidant/restrictive food intake disorder (ARFID), and other types of EDs (Others)), and the kinds of support they felt necessary to support these students. The encounter rates and the kinds of requested were obtained and compared, taking their confidence intervals into consideration. Results: The encounter rates for AN, BN, BED, ARFID, and Others were 48.4, 14.0, 8.4, 10.7, and 4.6 %, respectively. When classified by school type, AN, BN, BED, and ARFID had their highest encounter rates in senior high schools. Special needs schools had the highest rate for Others. The support most required for all ED types was "a list of medical/consultation institutions." Conclusions: Our results have clarified how to support Yogo teachers in the early detection and support of ED students. We found that the encounter rate of AN was the highest, and that it is effective to offer " a list of medical/consultation institutions" to junior and senior high schools where the encounter rates for AN are high.

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use.

We examined intelligence and memory in 25 healthy participants who had both prior magnetic resonance imaging (MRI) of gray matter volumes of medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC), along with diffusion tensor imaging (DTI) of posterior and anterior mOFC-rACC white matter microstructure, as assessed by fractional anisotropy (FA). Results showed distinct relationships between these basic structural brain parameters and higher cognition, highlighted by a highly significant correlation of left rACC gray matter volume with memory, and to a lesser extent, though still statistically significant, correlation of left posterior mOFC-rACC FA with intelligence. Regression analyses showed that left posterior mOFC-rACC connections and left rACC gray matter volume each contributed to intelligence, with left posterior mOFC-rACC FA uniquely accounting for between 20.43 and 24.99 % of the variance in intelligence, in comparison to 13.54 to 17.98 % uniquely explained by left rACC gray matter volume. For memory, only left rACC gray matter volume explained neuropsychological performance, uniquely accounting for a remarkably high portion of individual variation, ranging from 73.61 to 79.21 %. These results pointed to differential contributions of white mater microstructure connections and gray matter volumes to individual differences in intelligence and memory, respectively.

Introduction: The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ). Methods: After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions. Results: Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ. Conclusions: The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia. (C) 2015 Elsevier Ltd. All rights reserved.

Background: Patients with affective disorders exhibit changes in regional brain function and show abnormal social adaptation. However, to our knowledge, no near-infrared spectroscopy (NIRS) study has examined the relationship between these two phenomena longitudinally. This study examined the region specific functional abnormality associated with bipolar disorder (BD) and major depressive disorder (MDD), and the association between particular longitudinal changes in regional activation and social adaptation. Methods: We evaluated frontotemporal functioning during a verbal fluency Lest (VFT) for patients with BD (N=18), those with MDD (N=10), and healthy controls (HCs; N=14) using MRS. MRS measurements and the Social Adaptation Self-evaluation Scale (SASS) were administered twice with an interval of approximately 6 months. Results: The BD and MDD groups showed lesser activation than the HCs in the bilateral ventro-lateral prefrontal cortex and the anterior part of the temporal cortex (VLPFC/aTC). Longitudinal changes in SASS scores were positively associated with the extent of change in left VLPFC/aTC activation in the BD group and with right VLPFC/aTC activation in the MDD group. Limitations: Our small sample size limited statistical power, and the effect of medication and multiple comparisons cannot be excluded, although these effects were considered in the interpretation of the present results. Conclusion: Longitudinal increases of VLPFC/aTC activation were associated with improvement in social adaptation in patients with BD and those with MDD. MRS measurement could be a useful tool for objective evaluation of changes in social adaptation in BD and MDD. (C) 2015 Elsevier B.V. All rights reserved

ObjectivesNeuroimaging studies have suggested prefrontal dysfunction in response to cognitive activation in bipolar disorder (BD). However, its characteristics in manic states have not been well understood. Thus, we compared prefrontal hemodynamic responses during a cognitive task between hypomanic and depressive states in BD. We then longitudinally compared hypomanic and subsequent euthymic states. MethodsThe prefrontal function of 27 patients with BD (11 hypomanic and 16 depressed) and 12 age- and gender-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Hypomanic symptoms were assessed using the Young Mania Rating Scale. Among the 11 hypomanic patients, eight participated in the second NIRS measurement after their hypomanic symptoms resolved. ResultsVFT performance did not differ among hypomanic, depressed, and HC groups. Both BD groups exhibited significantly lower activation during the VFT than HCs in the broader bilateral prefrontal cortex. Hemodynamic changes in the left dorsolateral prefrontal cortex (DLPFC) in the hypomanic patients with BD were significantly larger than those in the depressed patients. In addition, hypomanic symptom severity was positively correlated with activation in the left DLPFC and frontopolar cortex in patients with BD. Follow-up measurement of the hypomanic patients revealed that prefrontal activation was decreased after hypomanic symptoms resolved. ConclusionsCombining cross-sectional and longitudinal assessments, the present results suggest that prefrontal hemodynamic responses associated with cognitive activation differ between hypomanic and depressive states in BD. NIRS measurement could be a useful tool for objectively evaluating state-dependent characteristics of prefrontal hemodynamics in BD.

Background: It is important to understand the neural basis of functional impairments in patients with bipolar disorder (BD) in order to be able to address the recovery. Recently, neurocognitive impairment emerged as a predictor of psychosocial function. A number of functional brain imaging studies have shown that social function is associated with activation of the prefrontal cortex during a cognitive task in healthy adults, and in patients with major depressive disorder and schizophrenia. However, few studies have been conducted in patients with BD. Methods: We performed multichannel near-infrared spectroscopy (NIRS) imaging to investigate the activation of the prefrontal cortex during a verbal fluency task (VFT). We also used the Social Adaptation Self-Evaluation Scale (SASS) to assess social functioning in patients with BD. Thirty-three depressed patients with BD and 65 age-, gender-and task performance-matched healthy controls (HCs) participated in this study. Results: Depressed patients with BD showed reduced activation in the broader bilateral prefrontal cortex during the VFT compared to HCs. Moreover, a significant positive correlation was observed between the total SASS scores and right prefrontal activation in patients with BD. In the SASS subscores, the interest and motivation factor was also positively correlated with frontopolar activation. Conclusions: These results suggest an association between social function and prefrontal activation in depressed patients with BD. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social function. (C) 2015 S. Karger AG, Basel

The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%-34% of the variance in IQ, in comparison to 11%-16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence.

Introduction: The medial orbitofrontal cortex (mOFC) and rostral part of the anterior cingulate cortex (rACC) are brain regions that are important in the neural network involving emotional processing and decision making, as well as playing an important role in social behavior and interaction. Considering the schizophrenia dysconnectivity hypothesis, observed abnormalities in emotional response and social behavior in schizophrenia might be associated with connectivity abnormalities between mOFC and rACC. Methods: Twenty-seven patients with chronic schizophrenia and 26 healthy controls were examined using diffusion tensor imaging (DTI). White matter properties in bilateral mOFC-rACC connections were examined using stochastic tractography, which has been shown to be among the most effective DTI methods for examining tracts between adjacent gray matter regions. Results: Reductions in fractional anisotropy (FA) were observed in left anterior mOFC-rACC connections (p < 0.0001), and bilateral posterior mOFC-rACC connections (left: p < 0.0001; right: p < 0.0001) in patients compared to controls. In addition, reduced FA in left posterior mOFC-rACC connections was associated with more severe anhedonia-asociality (R = -0.396, p = 0.041) and avolition-apathy (R = -0.426, p = 0.027) using the Scale for the Assessment of Negative Symptoms. Discussion: White matter abnormalities within connections between mOFC and rACC are associated with more severe anhedonia-asociality and avolition-apathy, which suggest that these brain regions may be important in understanding abnormal emotional responses and social behavior in patients with schizophrenia. (C) 2014 Elsevier B. V. All rights reserved.

In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3 T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p = 0.004), bilateral MFG (left: p = 0.007; right: p = 0.007), and bilateral IFG (left: p < 0.001; right: p = 0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R = -0.465, p = 0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R = 0.440, p = 0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching. (C) 2013 Elsevier B.V. All rights reserved.

Aim: The present study examined the effect of irritable bowel syndrome (IBS), cognitive appraisal of IBS, and anxiety sensitivity on anticipatory anxiety (AA) and agoraphobia (AG) in patients with panic disorder (PD). Methods: We examined 244 PD patients who completed a set of questionnaires that included the Rome II Modular Questionnaire to assess the presence of IBS, the Anxiety Sensitivity Index (ASI), the Cognitive Appraisal Rating Scale (CARS; assessing the cognitive appraisal of abdominal symptoms in four dimensions: commitment, appraisal of effect, appraisal of threat, and controllability), and items about the severity of AA and AG. The Mini International Neuropsychiatric Interview was used to diagnose AG and PD. Results: After excluding individuals with possible organic gastrointestinal diseases by using red flag items,' valid data were obtained from 174 participants, including 110 PD patients without IBS (PD/IBS[-]) and 64 with IBS (PD/IBS[+]). The PD/IBS[+] group had higher AA and higher comorbidity with AG than the PD/IBS[-] group. In the PD/IBS[+] group, the controllability score of CARS was significantly correlated with AA and ASI. Multiple regression analysis showed a significant effect of ASI but not of controllability on AA in PD/IBS[+] subjects. Conclusion: This study suggested that the presence of IBS may be related to agoraphobia and anticipatory anxiety in PD patients. Cognitive appraisal could be partly related to anticipatory anxiety in PD patients with IBS with anxiety sensitivity mediating this correlation.

Background: We examined the rate of bipolar I (BPD-I) and bipolar II disorders (BPD-II) in panic disorder (PD) patients, and compared clinical and psychological variables between PD patients with and without bipolar disorders (BPD). Methods: Participants were 649 Japanese patients with PD (215 men and 434 women, 38.49 +/- 10.40 years) at outpatient clinics for anxiety disorders. Constructive interviews using the Mini-International Neuropsychiatric Interview (MINI) were conducted to confirm the diagnosis of PD, agoraphobia, and BPD, as well as the presence and severity of suicide risk in each subject. Clinical records were also reviewed to confirm the diagnosis of PD and BPD. Participants then completed several questionnaires, including the State Trait Anxiety Inventory-Trait scale, the Anxiety Sensitivity Index, and the Revised Neuroticism-Extraversion- Openness Personality Inventory (NEO-PI-R). Results: We found that 22.34% of the PD patients had BPD (BPD-I: 5.24%, BPD-II: 17.10%). PD patients with BPD-I showed higher prevalence and severity of suicide risk, trait anxiety, anxiety sensitivity, and neuroticism, and lower agreeableness (subscales of the NEO-PI-R) than those with BPD-II and those without BPD. Limitation: First, we could not investigate the order of the onset of PD and BPD. Second, BPD patients without PD were not studied as another control group for PD patients with BPD. Conclusion: PD patients had high prevalence of BPD. Both PD patients with BPD-I and those with BPD-II had high severity of suicide risk, trait anxiety, anxiety sensitivity, neuroticism, and agreeableness, though these characteristics were more prominent in patients with BPD-I. (C) 2012 Elsevier B.V. All rights reserved.

Eye movement desensitization and reprocessing (EMDR) is an effective psychological intervention for posttraumatic stress disorder (PTSD) Trauma-related recall (Recall) with eye movements (EMs) is thought to reduce distress. However, the neural mechanisms underlying this process remain unknown. Thirteen patients with PTSD received EMDR treatment over the course of 2-10 weeks We assessed the change in hemoglobin concentration in the lateral prefrontal cortex (PFC) during Recall with and without EM using multi-channel near-infrared spectroscopy (NIBS). Clinical diagnosis and improvement were evaluated using the Clinician-Administered PTSD Scale. Recall with EM was associated with a significant decrease in oxygenated hemoglobin concentration ([oxy-Hb]) in the lateral PFC as compared with Recall without EM. Longitudinally, [oxy-Hb] during Recall significantly decreased and the amount of decrease was significantly correlated with clinical improvement when the post-treatment data was compared with that of the pre-treatment. Our results suggest that performing EM during Recall reduces the over-activity of the lateral PFC, which may be part of the biological basis for the efficacy of EMDR in PTSD. LAIRS may be a useful tool for objective assessment of psychological intervention in PTSD (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society All rights reserved

Background: Birth months have been shown to affect susceptibility to schizophrenia and other mental disorders, thus this factor could also affect predisposition to delinquency through biological effects on brain development and personality and/or through relative age effects at school. This study aimed to examine the relationship between birth-season and relative age at school on the risk of delinquency. Methods: We investigated the ratio of observed and expected births in winter/summer and that in the first/last months of the Japanese school year in 5008 young male Japanese delinquents. Results: No significant difference was found between observed and expected numbers of births in winter/summer or those in the first/last months of the school year. Conclusions: The present study did not provide evidence for any effect from season of birth or a relative age effect within the school year on the risk of delinquency in Japanese male teenagers. (c) 2007 Elsevier Inc. All rights reserved.

There is evidence of prefrontal cortex (PFC) dysfunction in patients with bipolar disorder (BP). Magnetic resonance and neuropathological studies show abnormalities of the brain microvasculature in patients with BP. However, the underlying biological mechanisms are not well understood. We investigated the relationship between activation of the PFC during a cognitive task and the vascular function in response to a physiological task in patients with BP. Fourteen euthymic patients with BP and 14 control subjects matched for age, sex, and education were recruited. We examined the response of the PFC during a verbal fluency task and during 5% CO2 inhalation using a 24-channel near-infrared spectroscopy imaging system to measure alteration of oxygenated and deoxygenated hemoglobin. The BP patients showed a significantly lower level of PFC activation during the cognitive task compared to the healthy controls, but the task-performance of the BP patients was not significantly different from that of the controls. The vascular response of the BP patients to CO2 was not significantly different from that of controls. This study suggests functional hypoactivation of the PFC during a cognitive load in patients with BP while they are in a euthymic state. The mechanism of this hypoactivation is different from that of vascular regulation in response to a physiological stimulus.

Objective: This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to satin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to satin. Methods: Thirty-eight victims of the 1995 Tokyo subway satin attack, all of whom had been treated in an emergency department for satin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. Results: The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). Interpretation: Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

Because of the difficulties of ascertaining episode of hypomania by past history of the patients, it is of clinical value to find variables which predict the development of bipolar II disorder in depressive patients. Taking advantage of relatively long hospitalization, the authors tried to elucidate fine clinical features of the soft bipolarity. The subjects were 39 patients with Major Depressive Episode, diagnosed according to the 4th edition of the Diagnostic and Statistical Manual criteria. Among them, 15 patients were diagnosed as bipolar II disorder (BPII), whereas 24 patients were with unipolar depression (UP), using a structured clinical interview to assess the mood spectrum (SCI-MOODS). In addition to ordinary clinical and demographic variables, the authors studied fine symptomatology of depression, premorbid personality, and interpersonal relationship. Continuous variables were analyzed by t-test. Categorical variables were tested by chi(2) analysis. In terms of premorbid personality, manic type (Zerssen) was found more frequently in BPII (UP 2/24, BPII 9/15, P < 0.05). Patients with BPII tended to show apparently quick disappearance of depressive symptoms (UP 2/24, BPII 9/15, P = 0.01). The most prominent result was a high prevalence of comorbidity of borderline personality disorder (BPD) among BPII (UP 0/24, BPII 6/15, P = 0.02). As Akiskal indicated that mood lability represents the most powerful predictor of hypomanias, patients with BPII showed quick response in mood to admission. The current subjects with BPII had high frequency of manic type of premorbid personality, indicating the usefulness of this variable for the prediction of hypomanias. Finally, the authors could observe development of BPD during hospitalization exclusively among BPII, to support the possibility of BPD as a state effect of BPII.

Clara cell secretory protein (CC16) is an anti-inflammatory protein expressed in the respiratory tract. Several studies have suggested the association between CC16 and mental disturbances, such as schizophrenia, depression, and post-traumatic stress disorder. In the present study, we investigated the association between the CC16 gene A38G polymorphism and personality traits in 214 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the genotypes and the scores of the NEO PI-R. or the STAI. The present results suggest that CC16 may not have a major role in the development of personality traits. (c) 2006 Elsevier Inc. All rights reserved.

Corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology of anxiety disorders and depression. Corticotropin-releasing hormone receptor 2 (CRHR2) is one of the receptors that mediate CRH signal. The purpose of the present study was to investigate the association between the CRHR2 gene and personality traits, evaluated using the Revised NEO Personality Inventory (NEO PI-R), in 243 healthy Japanese subjects. As a result, significant association was observed between the polymorphism in intron 2 (rs2267717) and Openness (P = 0.004, uncorrected, ANOVA), while no relationship was observed concerning Neuroticism. The present result suggests an association between CRHR2 and the personality trait of Openness.

Serotonin 2C receptor (5-HT2C), serotonin 6 receptor (5-HT6), and tryptophan hydroxylase-1 (TPH1) genes could be candidates for personality-related genes considering the role of serotonin in various mental functions and behavior. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the three serotonin-related genes, 5-HT2C, 5-HT6, and TPH1 genes, in relation to personality traits in the Japanese population. The Cys23Ser polymorphisms in the 5-HT2C gene, the 267T/C polymorphism of the 5-HT6 gene, and the 779A/C polymorphisms in the TPH1 gene were genotyped in 253 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the polymorphisms and the NEO PI-R or the STAI scores. The present results did not provide evidence for the association between the three serotonin-related genes and personality traits. The genes might not have major role in the development of personality traits, although further investigation with larger sample size may be recommended for conclusion. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

It has been suggested that symptoms of panic disorder may be significantly affected by seasonal factors including weather changes, although few studies have explored the issue. The purpose of the present paper was to investigate clinical data to examine sensitivity of panic disorder patients to seasonal changes and seasonal fluctuation of panic disorder symptoms. A self-rating questionnaire consisting of the Seasonal Pattern Assessment Questionnaire (SPAQ) and additional self-rating questions were analyzed in 146 Japanese patients (50 male, 96 female) with panic disorder (DSM-IV) at an outpatient clinic for anxiety disorder. The average of the Global Seasonality Scores (GSS) was 12.5 +/- 4.7 and 25.3% of the patients were suggested to suffer from seasonal affective disorder, according to the GSS. Frequency of the panic attack was found to fluctuate seasonally, with peaks in August and December (P = 0.005 and 0.01, chi(2) test). The present results indicate that panic disorder patients may be more sensitive to seasonal and meteorological factors than the general population and become more fragile in a specific season or months. This might assist in the development of preventive measures for the frequent recurrence of symptoms in panic disorder.

The association between the dopamine D4 receptor (DRD4) exon III polymorphism and personality trait of novelty seeking (NS) has been studied intensively. In the Japanese population, the results of the previous studies did not always coincide. In the present study, we investigated the association between the polymorphism and personality traits evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory (STAI) in 196 Japanese subjects. A meta-analysis of the present and previous Japanese studies was also conducted regarding NS. As a result, significant association was observed between the polymorphism and personality traits evaluated by using NEO PI-R as a whole (p = 0.022, MANCOVA). Subsequent analyses showed a significant association between short alleles (2-4 repeats) and higher scores for Neuroticism or its subscales, Anxiety, Depression, and Vulnerability (p = 0.015, 0.039, 0.021, and 0.008, respectively, uncorrected). No other significant difference in the scores for NEO PI-R was observed in the subsequent analyses. Significant association was also observed between the polymorphism and scores for STAI as a whole (p = 0.004, MANCOVA). Subsequent analyses did not show significant association, although a weak trend for the relation between the genotype consisting of short alleles and Trait Anxiety was observed (p = 0.10, uncorrected). The meta-analysis showed no significant association between the polymorphism and NS. Thus, the present study suggested the association between the short allele of the DRD4 exon III polymorphism and personality trait of Neuroticism in Japanese subjects. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Several molecular genetic studies have been conducted with regard to the association between catecholamine-related genes and personality traits. However, the results of replication studies did not always coincide. One of the possible reasons may be that the effect exerted by the individual gene is small. In the present study, we investigated the association between personality traits and systematic combination of functional polymorphisms in three genes that regulate the metabolism of catecholantines, namely, tyrosine hydroxylase (TH), monoamine oxidase A (MAOA), and catechol-O-methyltransferase (COMT). The (TCAT)(n) repeat in the TH gene, the promoter variable number tandem repeat (VNTR) in the MAOA gene, and Val 158Met in the COMT gene were genotyped in 256 healthy Japanese volunteers. Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). As a result, the score for Neuroticism increased, and those for Extraversion and Conscientiousness decreased according to the degree of functional polymorphic change, i.e., the lower synthesis/higher catalysis of catecholamines. A statistically significant difference was observed in the change of Extraversion (p = 0.04, after Bonferroni correction). These results may provide evidence for the association between metabolic change of catecholamines and personality traits, which may be due to the additive effect of the three genes. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

A growing number of functional neuroimaging studies on posttraumatic stress disorder(PTSD) have described the abnormal response of amygdala and prefrontalcortex to traumatic stimuli (Bremner et al, 1999 Shin et al, 2001 2004 Lanius2001 Zubieta et al 1999 Matsuo et al. 2003a). Furthermore, it has been reportedthat these abnormalities respond to treatment (Levin et al. 1999 Seedat et al. 2004 Carey et al. 2004). A large number of the studies on the prefrontal cortex in PTSDhave shown diminished activation of this region in response to trauma-related stimuli(Bremner et al. 1999 Shin et al. 2001, 2004 Lanius et al. 2001). In contrast,several studies have shown greater activation of the prefrontal cortex (Zubieta et al.1999 Matsuo et al. 2003a). In a positron emission tomography (PET) study (Bremneret al. 1999), combat veterans with PTSD showed diminished activation of themedial prefrontal cortex in response to trauma-related stimuli. Moreover, the decreasedblood flow in the medial prefrontal cortex was found to be negatively correlatedwith increased blood flow in the amygdala in response to the traumatic stimuliand positively correlated with the severity of the symptoms. This suggested thatinsufficient suppression of the medial prefrontal cortex in response to the overactivationof the amygdala could be considered as a pathophysiological model of PTSD(Shin et al. 2004). Functional magnetic resonance imaging (fMRI) studies haveshown similar findings (Lanius et al. 2001 Shin et al. 2001). Using single photonemission computed tomography (SPECT), Zubieta et al. (1999) examined regionalcerebral blood flow (rCBF) responses to a combat stress-related auditory stimulusin Vietnam war veterans with PTSD and found that PTSD patients showed a significantincrease in blood flow to the medial prefrontal cortex, which correlated at trend levels with psychophysical measures of stress response. In summary, abnormal activationof some parts of the prefrontal cortex might possibly be involved in thepathophysiology of PTSD.

A number of North American and European studies have observed a higher proportion of winter births in schizophrenia patients. Thus, seasonal fluctuation of unknown environmental factors may affect brain development in ways that alter susceptibility to schizophrenia. Specification of these factors may help elucidate the etiopathological mechanism of the disease, about which little is certain. A small number of studies have investigated this issue in Asian populations, and the findings are not as consistent as those of Western populations. No remarkable excess of winter births has been observed in Japanese or Korean studies, while some studies have reported a significant decrease of summer births. We further investigated the issue in Japanese patients with schizophrenia (n = 3927). No significant excess of winter births was observed, but a decrease in the summer births was found in male subjects. This is largely consistent with previous Japanese studies; however, when the subjects were confined to those born in a colder and higher latitude area of Japan (n = 1338), a consistent trend for both a winter increase, and a summer decrease, was found. However, the results did not consistently reach statistical significance, possibly due to the lack of statistical power. Environmental factors that correlate with latitude might play a role in the development of the seasonality of births in schizophrenia. Further studies in a larger sample size are required to test these possibilities. (c) 2004 Elsevier B.V. All rights reserved.

Previous studies on rapid eye movement sleep have demonstrated the effect of eye movement on emotional memory. However, the brain mechanism involved in the influence of the eye movement on the emotional recall remains unclear. We investigated the prefrontal response during an emotional memory recall with and without eye movement. Ten healthy volunteers were recruited. The changes in concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex were examined using near-infrared spectroscopy (NIRS) during a task that involved emotional recall with and without eye movement. Six participants demonstrated a significant increase in [oxy-Hb] during emotional recall, and the level of increase was reduced through repeated emotional recall with eye movement. The results suggest that eye movement is associated with a reduction in the hemodynamic response to emotional memory recall. © 2005 Elsevier Ireland Ltd. All rights reserved.

A number of studies have observed associations between the serotonin 2A (5-HT2A) receptor and mental disorders. Here, we investigated correlations between polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in healthy Japanese volunteers (n=239). The personality traits were evaluated using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C were in complete linkage disequilibrium. There was a tendency for associations between the genotype and the scores for Agreeableness, Conscientiousness and Neuroticism of the NEO PI-R (P=0.028, 0.039 and 0.062, respectively; analysis of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in Conscientiousness than the rest of the subjects. However, the results were statistically non-significant after Bonferroni's correction for multiple testing of the five scales of the NEO PI-R. Thus, the present study provided no evidence for statistically significant associations between the 5-HT2A polymorphisms and the personality traits. (c) 2005 Lippincott Williams A Wilkins.

Previous investigations of auditory P300 event-related potentials have provided electrophysiological evidence for attentional problems in patients with posttraumatic stress disorder (PTSD). The present study sought to evaluate the relationship between P300 deficits and underlying brain morphological abnormalities in never-treated, comorbidity-free patients with PTSD following the Tokyo subway sarin attack. Out of 47 victims recruited, 8 victims with PTSD and 13 victims without PTSD were identified. Correlational analyses were performed between auditory P300 amplitude at Pz electrode site elicited in an oddball task and anterior cingulate gray matter volume that was shown to be reduced in our previous study using voxel-based morphometry on magnetic resonance imaging. Victims with PTSD showed significantly lower amplitudes of P300 compared with victims without PTSD, and the lower P300 amplitudes at Pz were significantly associated with higher avoidance/numbing scores in the PTSD group. Furthermore, in the PTSD group only, the P300 amplitudes showed a trend toward significant positive correlation with voxel densities of the anterior cingulate cortex gray matter. These results provide the first evidence that electrophysiological deficits of controlled attention observed in patients with PTSD may be linked to underlying brain morphological abnormalities. (C) 2005 Elsevier Inc. All rights reserved.

Sarin gas was dispersed in a Tokyo subway in 1995. This study investigates the mental and somatic symptoms of the 34 victims 5 years after the attack. Structured interviews (Clinician-Administered Post-Traumatic Stress Disorder [CAPS] and Mini International Neuropsychiatric Interview) and self-rating questionnaires were used to assess the symptoms. Not only post-traumatic stress disorder (PTSD) but also non-specific mental symptoms persisted in the victims at a high rate. A total of 11 victims were diagnosed with current or lifetime PTSD according to CAPS. Victims with PTSD showed higher anxiety levels and more visual memory impairment. A significant correlation between the total score of Impact of Event Scale-Revised (IES-R) and CAPS was found, indicating that IES-R is a useful tool for evaluating PTSD.

The present study investigated frequency of post-traumatic stress disorder (PTSD) in incarcerated juvenile delinquents in Japan. The presence of overwhelming traumatic experiences, which fulfilled the DSM-IV criterion A for PTSD, was evaluated using a self-report questionnaire in 251 delinquents (206 males and 45 females). The structured interview using the Clinician-administered PTSD Scale for DSM-IV (CAPS) was administered to those with the experiences. A substantial portion (36%) of the delinquents reported experiences of exposure to such overwhelming traumatic events, which fulfilled the criterion A. Among those who met the criterion A, 48 subjects (40 males and eight females) received the CAPS interview. Ten (21%) out of 48 were diagnosed with current or past history of full PTSD. Three subjects out of the 10 were currently diagnosed with full PTSD. Another 10 subjects out of 48 (21%) had fulfilled the criteria for current or past history of partial PTSD. Among the 10, one was diagnosed as currently suffering from partial PTSD. In females, frequencies of the past history were quite high (50% for full PTSD and 25% for partial PTSD in the eight subjects), while none was currently diagnosed with PTSD.

The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population. (C) 2004 Wiley-Liss, Inc.

Mitochondria is the major site of energy production in cells, therefore, mitochondrial abnormality may affect functions of organs including the brain, which constantly requires high levels of energy consumption. Previous studies have suggested a role of mitochondria and their DNA polymorphisms in neuro-psychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia and bipolar mood disorder. Thus, we hypothesized that mitochondrial DNA polymorphisms might be related with the development of personality. The present study investigated a role of two mitochondrial DNA polymorphisms, the C5178A and A10398G, in personality traits evaluated using the NEO PI-R scores in 238 healthy Japanese volunteers. Subjects with the 5178A genotype showed significantly higher extraversion score than those with the 5178C genotype (P = 0.027), while no significant association was observed between the C5178A polymorphism and other scores. No significant association was found between the A10398G polymorphism and any scores Regarding the 5178-10398 haplotype, the score of extraversion, not other scores, was significantly associated with the A-G haplotype (P = 0.042). Although further studies are recommended for the confirmation, the result may suggest a role of the mitochondrial DNA polymorphism in the personality trait. (C) 2004 Wiley-Liss, Inc.

The NOTCH4 gene is located at 6p21.3 and involved in the development and patterning of the central nervous systems. Recently, Wei and Hemmings [2000] observed that the gene was associated with schizophrenia. Subsequent to the report, several studies investigated the gene in schizophrenia, with controversial and inconclusive results. In the present study, we investigated six polymorphisms (SNPs 1-5 and a CTG repeat) of the gene in Japanese subjects with schizophrenia (n = 284) and the same number of controls. The polymorphisms include SNP5, which has been observed to be associated with schizophrenia in a Chinese population and two new SNPs 3-4 adjacent to SNP5, in addition to the SNPs 1-2 and the CTG repeat, which were suggested for the association with the disease in the previous study. As a result, no significant difference in genotypic distributions or allelic frequencies of the six polymorphisms of the gene was observed between the patients and the controls. Also, no significant difference was found in frequencies of haplotypes of the six polymorphisms between the patients and the controls. However, the distribution of SNP2 was significantly deviated from Hardy-Weinberg equilibrium in the patients (P = 0.000986), not in the controls, which could be a chance or due to an association of SNP2 with the disease. In conclusion, the present study provided no clear evidence for an association between the NOTCH4 gene and schizophrenia in the Japanese population. © 2004 Wiley-Liss, Inc.

Seasonality of births in schizophrenia and other mental disorders has been consistently observed. This may be through effects of unknown environmental factors that seasonally fluctuate on the brain development. The effects may affect cognitive function of the brain and behavioral characteristics that might be correlated with the development of personality not only in patients with mental disorders but also in healthy subjects. We, therefore, investigated the effects of season of birth on personality traits in healthy Japanese adults (n = 397). Personality traits were evaluated using the NEO Personality Inventory-Revised (NEO PI-R). A trend for lower Agreeableness in subjects born during winter (December to February) than other subjects was observed (P = 0.036, after correction for the multiple testing, multiple regression analysis adjusting for age and sex). Other major factors of the NEO PI-R, including Neuroticism, Extraversion, Openness and Conscientiousness, were not affected by season of birth. Further studies may be recommended to confirm the results, considering the relatively limited sample size. Evaluation of cognitive functions and behaviors using other measures including event-related potentials and functional MRI may also help the interpretation of the present result. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Mitochondria is the major site of energy production in cells, therefore, mitochondrial abnormality may affect functions of organs including the brain, which constantly requires high levels of energy consumption. Previous studies have suggested a role of mitochondria and their DNA polymorphisms in neuro-psychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia and bipolar mood disorder. Thus, we hypothesized that mitochondrial DNA polymorphisms might be related with the development of personality. The present study investigated a role of two mitochondrial DNA polymorphisms, the C5178A and A10398G, in personality traits evaluated using the NEO PI-R scores in 238 healthy Japanese volunteers. Subjects with the 5178A genotype showed significantly higher extraversion score than those with the 5178C genotype (P = 0.027), while no significant association was observed between the C5178A polymorphism and other scores. No significant association was found between the A10398G polymorphism and any scores. Regarding the 5178-10398 haplotype, the score of extraversion, not other scores, was significantly associated with the A-G haplotype (P = 0.042). Although further studies are recommended for the confirmation, the result may suggest a role of the mitochondrial DNA polymorphism in the personality trait. © 2004 Wiley-Liss, Inc.