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There is sometimes a divergence between brain atrophy and impairments in cognitive function. The present study aimed to assess the relationship between cognitive function and the grey-matter brain healthcare quotient (GM-BHQ), which represents brain volume as a deviation value. In addition, we aimed to investigate lifestyle factors that can help maintain cognitive function despite brain atrophy. A total of 1,757 adults included in a Japanese MRI brain screening cohort underwent MRI. We classified the participants into two age groups: under 65 years old (young adult/middle age group) and over 64 years old (elder group). The GM-BHQ was more strongly correlated with cognitive function in the young adult/middle age group than in the elder group (p .01). Regression analysis revealed that years of education was associated with the maintenance of cognitive function despite brain atrophy (p .05). In conclusion, our findings suggest that the relationship between brain volume and cognitive function becomes more obscure with age.

Background: Gait, speech, and drawing behaviors have been shown to be sensitive to the diagnosis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, previous studies focused on only analyzing individual behavioral modalities, although these studies suggested that each of these modalities may capture different profiles of cognitive impairments associated with AD. Objective: We aimed to investigate if combining behavioral data of gait, speech, and drawing can improve classification performance compared with the use of individual modality and if each of these behavioral data can be associated with different cognitive and clinical measures for the diagnosis of AD and MCI. Methods: Behavioral data of gait, speech, and drawing were acquired from 118 AD, MCI, and cognitively normal (CN) participants. Results: Combining all three behavioral modalities achieved 93.0% accuracy for classifying AD, MCI, and CN, and only 81.9% when using the best individual behavioral modality. Each of these behavioral modalities was statistically significantly associated with different cognitive and clinical measures for diagnosing AD and MCI. Conclusion: Our findings indicate that these behaviors provide different and complementary information about cognitive impairments such that classification of AD and MCI is superior to using either in isolation.

Central post-stroke pain (CPSP) is a chronic pain caused by stroke lesions of somatosensory pathways. Several brain imaging studies among patients with CPSP demonstrate that the pathophysiological mechanism underlying this condition is the maladaptive plasticity of pain-related brain regions. However, the temporal profile of the regional plastic changes, as suggested by brain imaging of CPSP patients, as well as their cellular basis, is unknown. To investigate these issues, we performed voxel-based morphometry (VBM) using T1-weighted magnetic resonance imaging and immunohistochemical analysis with our established CPSP monkey model. From 8 weeks after a hemorrhagic lesion to the unilateral ventral posterolateral nucleus of the thalamus, the monkeys exhibited significant behavioral changes that were interpreted as reflecting allodynia. The present VBM results revealed a decrease in gray matter volume in the pain-related areas after several weeks following the lesion. Furthermore, immunohistochemical staining in the ipsilesional posterior insular cortex (ipsi-PIC) and secondary somatosensory cortex (ipsi-SII), where the significant reduction in gray matter volume was observed in the VBM result, displayed a significant reduction in both excitatory and inhibitory synaptic terminals compared to intact monkeys. Our results suggest that progressive changes in neuronal morphology, including synaptic loss in the ipsi-PIC/SII, are involved in theCPSP.

Aim Matrix metalloproteinase‐9 (MMP‐9) has been shown to modulate synaptic plasticity and may contribute to the pathophysiology of schizophrenia. This study investigated the peripheral levels of MMP‐9 and its association with cognitive functions in patients with schizophrenia to see the possible involvement of MMP‐9 in pathophysiology of schizophrenia, especially in cognitive decline. Methods We measured the plasma levels of MMP‐9 in 257 healthy controls and 249 patients with schizophrenia, including antipsychotic drug–free patients. We also explored the possible association between plasma MMP‐9 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition (WAIS‐ III), the Wechsler Memory Scale‐Revised (WMS‐R), and the Rey Auditory Verbal Learning Test (AVLT). Results We found that the plasma levels of MMP‐9 were significantly higher in patients with schizophrenia, including antipsychotic drug–free patients, than in healthy controls. We found a significant negative association between plasma MMP‐9 levels and cognitive performance in controls and patients with schizophrenia. Conclusion Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased MMP‐9 levels are associated with cognitive impairment., Plasma levels of MMP‐9 were significantly higher in patients with schizophrenia and significant negative association between plasma MMP‐9 levels and cognitive performance was observed in controls and patients with schizophrenia.

The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders. This article is protected by copyright. All rights reserved.

Aim Increased brain gyrification in diverse cortical regions has been reported in patients with schizophrenia, possibly reflecting deviations in early neurodevelopment. However, it remains unknown whether patients with schizotypal disorder exhibit similar changes. Methods This magnetic resonance imaging study investigated brain gyrification in 46 patients with schizotypal disorder (29 male, 17 female), 101 patients with schizophrenia (55 male, 46 female), and 77 healthy controls (44 male, 33 female). T1-weighted magnetic resonance images were obtained for each participant. Using FreeSurfer software, the local gyrification index (LGI) of the entire cortex was compared across the groups. Results Both schizophrenia and schizotypal disorder patients showed a significantly higher LGI in diverse cortical regions, including the bilateral prefrontal and left parietal cortices, as compared with controls, but its extent was broader in schizophrenia especially for the right prefrontal and left occipital regions. No significant correlations were found between the LGI and clinical variables (e.g., symptom severity, medication) for either of the patient groups. Conclusion Increased LGI in the frontoparietal regions was common to both patient groups and might represent vulnerability to schizophrenia, while more diverse changes in schizophrenia patients might be associated with the manifestation of florid psychosis.

Background The differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is particularly important because DLB patients respond better to cholinesterase inhibitors but sometimes exhibit sensitivity to neuroleptics, which may cause worsening of clinical status. Antemortem voxel-based morphometry (VBM) using structural MRI has previously revealed that patients with DLB have normal hippocampal volume, but atrophy in the dorsal mesopontine area. Objectives The aim of this multicenter study was to determine whether VBM of the brain stem in addition to that of medial temporal lobe structures improves the differential diagnosis of AD and DLB. Methods We retrospectively chose 624 patients who were clinically diagnosed with either DLB (239 patients) or AD (385 patients) from 10 institutes using different MR scanners with different magnetic field strengths. In all cases, VBM was performed on 3D T1-weighted images. The degree of local atrophy was calculated using Z-score by comparison with a database of normal volumes of interest (VOIs) in medial temporal lobe (MTL) and the dorsal brain stem (DBS). The discrimination of DLB and AD was evaluated using Z-score values in these two VOIs. MRI data from 414 patients were used as the training data set to determine the classification criteria, with the MRI data from the remaining 210 patients used as the test data set. Results The DLB and AD patients did not differ with respect to mean age or Mini-Mental State Examination scores. Z-index scores showed that there was significantly more atrophy in MTL of AD patients, compared to DLB patients and in DBS of DLB patients, compared to AD patients. The discrimination accuracies of VBM were 63.3% in the test data set and 73.4% in the training data set. Conclusion VBM of DBS in addition to that of MTL improves the differentiation of DLB and AD.

Social support networks are considered beneficial for post-disaster survivor mental health. However, there are family and non-family networks, and support can be received or provided. Therefore, their complex contribution to wellbeing requires analysis. Researching elderly residents of Joso City NE of Tokyo ( N = 1182 [female: n = 618], Age M = 69.76y, SD = 6.10y) who experienced severe flooding in September 2015 investigated data for mental health outcomes of depression (K6), trauma (IES-R), and existence of recent worry from evacuation and house damage. An original instrument tapped support source and direction, controlled to examine mental health symptom changes. House damage was a higher mental health predictor (η p 2 = .10–.16) than evacuation (η p 2 = .033–.093). Results indicated family social support may buffer mental health outcomes, but non-family social support may burden them. Overall support network size also indicated burdening compared to social support receiving-providing imbalance.

BackgroundWith the rapid growth of the older adult population worldwide, car accidents involving this population group have become an increasingly serious problem. Cognitive impairment, which is assessed using neuropsychological tests, has been reported as a risk factor for being involved in car accidents; however, it remains unclear whether this risk can be predicted using daily behavior data.ObjectiveThe objective of this study was to investigate whether speech data that can be collected in everyday life can be used to predict the risk of an older driver being involved in a car accident.MethodsAt baseline, we collected (1) speech data during interactions with a voice assistant and (2) cognitive assessment data—neuropsychological tests (Mini-Mental State Examination, revised Wechsler immediate and delayed logical memory, Frontal Assessment Battery, trail making test-parts A and B, and Clock Drawing Test), Geriatric Depression Scale, magnetic resonance imaging, and demographics (age, sex, education)—from older adults. Approximately one-and-a-half years later, we followed up to collect information about their driving experiences (with respect to car accidents) using a questionnaire. We investigated the association between speech data and future accident risk using statistical analysis and machine learning models.ResultsWe found that older drivers (n=60) with accident or near-accident experiences had statistically discernible differences in speech features that suggest cognitive impairment such as reduced speech rate (P=.048) and increased response time (P=.040). Moreover, the model that used speech features could predict future accident or near-accident experiences with 81.7% accuracy, which was 6.7% higher than that using cognitive assessment data, and could achieve up to 88.3% accuracy when the model used both types of data.ConclusionsOur study provides the first empirical results that suggest analysis of speech data recorded during interactions with voice assistants could help predict future accident risk for older drivers by capturing subtle impairments in cognitive function.

Health-monitoring technologies for automatically detecting the early signs of Alzheimer's disease (AD) have become increasingly important. Speech responses to neuropsychological tasks have been used for quantifying changes resulting from AD and differentiating AD and mild cognitive impairment (MCI) from cognitively normal (CN). However, whether and how other types of speech tasks with less burden on older adults could be used for detecting early signs of AD remains unexplored. In this study, we developed a tablet-based application and compared speech responses to daily life questions with those to neuropsychological tasks in terms of differentiating MCI from CN. We found that in daily life questions, around 80% of speech features showing significant differences between CN and MCI overlapped those showing significant differences in both our study and other studies using neuropsychological tasks, but the number of significantly different features as well as their effect sizes from life questions decreased compared with those from neuropsychological tasks. On the other hand, the results of classification models for detecting MCI by using the speech features showed that daily life questions could achieve high accuracy, i.e., 86.4%, comparable to neuropsychological tasks by using eight questions against all five neuropsychological tasks. Our results indicate that, while daily life questions may elicit weaker but statistically discernable differences in speech responses resulting from MCI than neuropsychological tasks, combining them could be useful for detecting MCI with comparable performance to using neuropsychological tasks, which could help develop health-monitoring technologies for early detection of AD in a less burdensome manner.

Reduced hippocampal volumes feature prominently in schizophrenia patients (SCZ). Although several studies have investigated hippocampal volume alterations between unaffected first-degree relatives (FR) of SCZ and healthy controls (HC), the results were inconsistent. Furthermore, it remains unclear whether FR have specific alterations in hippocampal subfield volumes. Three-Tesla T1-weighted MP-RAGE brain scans were collected from 347 subjects (138 SCZ, 47 FR and 162 HC) and processed using the hippocampal subfields algorithm in FreeSurfer v6.0. We investigated volumetric differences in the twelve hippocampal subfields bilaterally among SCZ, FR and HC. SCZ displayed bilateral reductions in whole hippocampal volume compared with FR and HC. The hippocampal volumes of FR did not differ from those of HC but exceeded those observed in SCZ. We found volumetric differences in specific hippocampal subfields, including the CA1, hippocampal fissure, presubiculum, molecular layer, fimbria and hippocampal-amygdala transitional area, among diagnostic groups. These alterations arose from differences in the hippocampal subfield volumes between SCZ and the other two diagnostic groups. However, right hippocampal fissure volumes linearly increased among the groups. In contrast, no significant volumetric differences were found in other hippocampal subfields between HC and FR. There were no significant intergroup differences in laterality in any hippocampal subfield volumes and no significant correlations between hippocampal subfield volumes and illness duration, psychiatric symptoms, antipsychotics or premorbid IQ in SCZ. Our findings suggest that volumetric alterations in hippocampal subfields (except the hippocampal fissure) in SCZ could be stable phenomena that are present at illness onset and minimally affected by antipsychotics.

Human social activities are realized by a synergy of neuronal activity over various regions of the brain, which is supported by their connectivity. In the present study, we examined associations between social activities, represented by work hours, and brain connectivity as quantified using diffusion tensor imaging (DTI). In 483 healthy participants, DTI analysis was performed using 3 T magnetic resonance imaging, and work hours were calculated, considering hours of paid employment (the “Work for Pay” category), hours of housework (the “Work at Home” category), and hours of school-related study (the “Student” category). The correlations between each class of work time and DTI indices were analyzed. The mean diffusivity (MD) values of the anterior limb of the internal capsule (ALIC) and the superior fronto-occipital fasciculus (SFO) were negatively correlated with total work hours (ALIC: r = -0.192, p = 2.3 × 10−5; SFO: r = -0.161, p = 3.8 × 10-4). We also found that the MD values of the ALIC and the SFO were correlated with work hours in the Work for Pay category (ALIC: r = -0.211, p = 3.2 × 10-6; SFO: r = -0.163, p = 3.4 × 10-4) but not with those in the Work at Home category or the Student category. These results suggest that social activity is associated with the white matter microstructure of the ALIC and the SFO. The main difference between “Work for Pay” and the other two social activities appears to be the type of motivation—for example, external versus internal. Therefore, the white matter microstructure of the ALIC and SFO may be related to externally motivated social activities.

Aim: Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and leads to dementia. AD is characterized by progressive declines in memory and, as the disease progresses, language dysfunction. Although it has been reported that AD patients show progressive aphasia, no study has examined the relationship between language functions estimated by the Standard Language Test for Aphasia (SLTA) and brain network connectivity in Japanese AD patients. If present, such a relationship would be of particular interest because Japanese speakers are accustomed to mingling ideography and phonography. Methods: 22 Japanese patients with AD who underwent 1.5-tesla MRI scan and SLTA, the scale for speech and reading impairment, participated in this study. We computed brain network connectivity metrics such as degree, betweenness centrality, and clustering coefficient, and estimated their relationships with the subscores of SLTA. Results: There was a significant negative correlation between the score for “reading aloud Kanji words” and the clustering coefficient in the left inferior temporal region, bilateral hippocampal regions, and right parietotemporal region. We also found a significant negative correlation between the score for “auditory comprehension of words” and the clustering coefficient in the left prefrontal region. No significant relationship was found between the other SLTA scores and the network metrics. Conclusions: Our data suggest relationships between reading impairments and regional brain network connectivity in Japanese patients with AD. The brain connectome may provide adjunct biological information that could improve our understanding of reading impairment.

Background Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)” project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia. Methods A cross‐sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs. Results Forty‐three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%). Conclusions In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future., This study reports the prescription pattern in schizophrenia in Japan from EGUIDE (Effectiveness of Guideline for Dissemination and Education in psychiatric treatment) project. A cross‐sectional, case record survey conducted, involving 1164 patients with schizophrenia at the time of discharge. Forty‐three percent of patients received antipsychotic polypharmacy. Based on the results, we plan to report changes in the effectiveness of education in the EGUIDE project in the future.

Patients with schizophrenia show severe impairment in social function and have difficulty in their daily social life. Although a recent large-scale multicenter study revealed alterations in white matter microstructures, the association between these anatomical changes and social dysfunction in schizophrenia remains unknown. Therefore, we investigated the association between the white matter integrity of regions of interest and social function in schizophrenia. A total of 149 patients with schizophrenia and 602 healthy comparison subjects (HCS) underwent DTI and completed the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-Third Edition and the Finance subscale of the University of California, San Diego, Performance-Based Skills Assessment Brief, as social indices of interest. The fractional anisotropy (FA) in the anterior corona radiata and corpus callosum was significantly lower in patients than in HCS, and the radial diffusivity (RD) in the anterior corona radiata and corpus callosum was significantly higher in patients. The Picture Arrangement and Finance scores were both significantly impaired in patients. The effect of the FA of the right anterior corona radiata on the Finance score and the Picture Arrangement score, of the RD of the right anterior corona radiata on the Picture Arrangement score, and of the RD of the corpus callosum on the Picture Arrangement score were significant. In conclusion, our results confirmed the association between structural connectivity in the right frontal white matter and corpus callosum and social function in schizophrenia. These findings may provide a foundation for developing an intervention for functional recovery in schizophrenia.

Background An imbalance in the inflammatory tumor necrosis factor system, including soluble tumor necrosis factor receptor 2 (sTNFR2), may contribute to the pathophysiology of schizophrenia. Methods We measured the plasma levels of sTNFR2 in 256 healthy controls and 250 patients with schizophrenia including antipsychotic drug-free patients and treatment-resistant patients. We also explored the possible association between plasma sTNFR2 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, and the Rey Auditory Verbal Learning Test. An association between plasma sTNFR2 levels and hippocampal volume in controls and patients with schizophrenia was also investigated via MRI. Results We found that the plasma levels of sTNFR2 were significantly higher in patients with schizophrenia, including both antipsychotic drug-free patients and treatment-resistant patients. We found a significant negative association between plasma sTNFR2 levels and cognitive performance in controls and patients with schizophrenia. Hippocampal volume was also negatively associated with plasma sTNFR2 levels in patients with schizophrenia. Conclusion Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased sTNFR2 levels are associated with a smaller hippocampal volume and cognitive impairment.

Background The effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis. Methods Imaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed. Results Daily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes. Discussion A large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication., Graphical abstract Image 2, Highlights • The imaging data as well as prescription data and demographics from 778 patients with schizophrenia from 11 institutions were included. • The effect of protocol was cooperated as random-effect in the linear mixed-effect model. • Significant positive association were found between daily dose of antipsychotics and left globus pallidus volume. • Significant negative association was found between daily dose of antipsychotics and right hippocampus volume. • Significant positive associations were found between duration of illness and bilateral volumes of globus pallidus.

Background With the spread of COVID-19, the deterioration of public mental health has become a major global and social problem. Objective The purpose of this study was to elucidate the relationship between the 3 mental health problems associated with COVID-19, that is, perceived stress, severe mental distress, and anxiety symptoms, and the various demographic factors, including occupation. Methods A nationwide web-based questionnaire survey was conducted in Japan from August 4 to 31, 2020. In addition to sociodemographic data, the degrees of perceived stress, severe mental distress, and anxiety symptoms associated with COVID-19 were measured. After performing a descriptive statistical analysis, factors related to stress, severe mental distress, and anxiety symptoms were analyzed using logistic regression analysis. Results A total of 8203 respondents submitted survey responses, among whom 34.9% (2861/8203) felt intense stress associated with COVID-19, 17.1% (1403/8203) were depressed, and 13.5% (1110/8203) had severe anxiety symptoms. The logistic regression analysis showed that each of the 3 mental health problems were prevalent in females, nonbinary gender, people in their 50s, 60s and older, respondents who visited psychiatrists, and those currently in psychiatric care. Severe mental distress and anxiety symptoms were associated with the number of effective lifestyle coping strategies during the lockdown period. Severe mental distress was only prevalent in teenagers and respondents in their 20s, as students tended to develop stress and severe mental distress. With regard to occupation, working in nursing care and welfare, education and research, and medical and health sectors was associated with stress; however, working in these occupations was not associated with severe mental distress and anxiety symptoms. Unemployment was associated with severe mental distress and anxiety symptoms. All 3 mental health problems were prevalent in part-time workers and those working in entertainment and arts sectors. Conclusions Gender, age, occupation, history of psychiatric visits, and stress coping mechanisms were associated with mental health during the COVID-19 pandemic, but their associations with stress, severe mental distress, and anxiety symptoms differed. In addition, the actual state of mental health varied according to the respondents’ occupation. It is necessary to consider the impact of the COVID-19 pandemic on mental health not only at the individual level but also at the occupational level.

To develop a suitable automobile design as per each driver’s characteristics and state, it is important to understand the brain function in acquiring driving skills. Reportedly, the brain structures of professionals, such as athletes and musicians, and those who have received training in special skills, undergo changes with training. However, the development process of the brain in terms of acquiring driving skills has not yet been clarified. In this study, we evaluated the effects of driving training on the brain and observed an increase in the volume of the right cerebellum after short-term training (3 days). The right cerebellum is responsible for controlling the right hand and right foot, which are important for driving. Drivers train to control a vehicle smoothly at high speeds at gymkhana and pylon slalom courses, which are often used in motor sports. The brain structure was analyzed before and after training using magnetic resonance imaging. Voxel-based morphometry was used to assess possible structural changes. First, the lap times after training were clearly shortened and vehicle dynamics were more stable, indicating that the drivers’ skill level clearly improved. Second, brain structural analysis revealed a volumetric increase in the right cerebellum. The cerebellum is involved in the process of learning sensory motor skills, such as smooth steering and pedal operations, driving course shape, and vehicle size perception. These results suggest a new inner model for driving operation and support the hypothesis that motor learning affects the cerebellum during vehicle driving training.

Recent studies examining electroconvulsive therapy (ECT) have reported that early sessions can induce rapid antidepressant and antipsychotic effects, and the early termination of ECT was reported to increase the risk of relapse. We hypothesized that different neural mechanisms associated with the therapeutic effects of ECT may be involved in the different responses observed during the early and late periods of ECT treatment. We investigated whether these antidepressant and antipsychotic effects were associated with temporally and spatially different regional gray matter volume (GMV) changes during ECT. Fourteen patients with major depressive disorder, with or without psychotic features, underwent 3-Tesla structural magnetic resonance imaging scans before (time point [Tp] 1), after the fifth or sixth ECT session (Tp2), and after ECT completion (Tp3). We investigated the regions in which GMV changed between Tp1 and Tp2, Tp2 and Tp3, and Tp1 and Tp3 using voxel-based morphometry. In addition, we investigated the association between regional GMV changes and improvement in depressive or psychotic symptoms. GMV increase in the left superior and inferior temporal gyrus during Tp1–Tp2 was associated with improvement in psychotic symptoms (P P

Obsessive-compulsive disorder (OCD) is known as a clinically heterogeneous disorder characterized by symptom dimensions. Although substantial numbers of neuroimaging studies have demonstrated the presence of brain abnormalities in OCD, their results are controversial. The clinical heterogeneity of OCD could be one of the reasons for this. It has been hypothesized that certain brain regions contributed to the respective obsessive-compulsive dimensions. In this study, we investigated the relationship between symptom dimensions of OCD and brain morphology using voxel-based morphometry to discover the specific regions showing alterations in the respective dimensions of obsessive-compulsive symptoms. The severities of symptom dimensions in thirty-three patients with OCD were assessed using Obsessive-Compulsive Inventory-Revised (OCI-R). Along with numerous MRI studies pointing out brain abnormalities in autistic spectrum disorder (ASD) patients, a previous study reported a positive correlation between ASD traits and regional gray matter volume in the left dorsolateral prefrontal cortex and amygdala in OCD patients. We investigated the correlation between gray and white matter volumes at the whole brain level and each symptom dimension score, treating all remaining dimension scores, age, gender, and ASD traits as confounding covariates. Our results revealed a significant negative correlation between washing symptom dimension score and gray matter volume in the right thalamus and a significant negative correlation between hoarding symptom dimension score and white matter volume in the left angular gyrus. Although our result was preliminary, our findings indicated that there were specific brain regions in gray and white matter that contributed to symptom dimensions in OCD patients.

ObjectiveTo investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations.MethodsWe applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC.ResultsThere were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD.ConclusionOur study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

Aims We aimed to investigate the association between general mental health and attitudes toward suicide of participants in suicide-prevention gatekeeper training programs. Methods We conducted a number of half day training seminars within a suicide prevention program addressing gatekeepers. Participants filled in two questionnaires, one measuring general health (General Health Questionnaire, GHQ-12), and one measuring attitudes towards suicide (ATTS). Results The total sample size of participants was 230, of whom 115 completed questionnaires. There were no significant differences in demographic backgrounds between the good mental health (GHQ-12 ≤ 4) and the poor mental health (GHQ-12 ≥ 5) groups. The poor mental health group was more likely to think that people have the right to commit suicide. Conclusion There was a difference in attitudes toward suicide between the good mental health and the poor mental health groups, indicating that attention should be paid to participants' mental health when conducting suicide-prevention gatekeeper training.

Stress is associated with a greater risk for various health problems including reduced gray matter volume (GMV) and density in a number of brain regions. Previous studies show that neuroimaging could be a means to objectively evaluate stress. However, to date, no definite neuroimaging-derived measures are available to detect stress. In this research we used the gray-matter brain healthcare quotient (GM-BHQ), an MRI-based quotient for monitoring brain health based on GMV, as an objective scale to measure the association of stress with the whole brain. We recruited 63 healthy adults to acquire structural T1-weighted images and stress levels evaluated using three representative stress scales: the Profile of Mood States (POMS), Perceived Stress Scale (PSS) and Chalder Fatigue Scale (CFS). We found that the GM-BHQ was sensitive to fatigue and the interaction between fatigue and stress.

OBJECTIVES Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric disorders, with some speculating that a reason for difficulty in its treatment might be its coexistence with autism spectrum. We investigated the tendency for autistic spectrum disorders (ASD) in patients with OCD from a neuroimaging point of view using voxel-based morphometry. METHODS We acquired T1-weighted images from 20 patients with OCD and 30 healthy controls and investigated the difference in regional volume between the groups as well as the correlation between Autism-Spectrum Quotient (AQ) scores and regional cerebral volumes of patients with OCD. RESULTS Volumes in the bilateral middle frontal gyri were significantly decreased in patients with OCD compared to controls. Correlational analysis showed significant positive correlations between AQ scores and regional gray matter (GM) volumes in the left dorsolateral prefrontal cortex (DLPFC) and left amygdala. Furthermore, GM volumes of these regions were positively correlated with each other. CONCLUSIONS The positive correlation of ASD traits in patients with OCD with regional GM volumes in the left DLPFC and amygdala could reflect the heterogeneity of patient symptoms. Our results suggest that differences in GM volume might allow classification of patients with OCD for appropriate therapy based on their particular traits.

Background: Previously, we reported on vascular cognitive impairment (VCI) templates, consisting of patients with VCI associated with carotid stenosis (>60%) using a quantitative electroencephalographic (EEG) technique called neuronal activity topography (NAT). Here using the VCI templates, we investigated the hypothesis that internal carotid artery–intima-media thickness (ICA–IMT) is associated with EEG spectrum intensity (sNAT) and spectrum steepness (vNAT)., Methods: A total of 221 community-dwelling elderly subjects were recruited. Four groups were classified according to quartiles of ICA–IMT as assessed by ultrasonography: control group A, normal (≤0.9 mm); group B, mild atherosclerosis (1−1.1 mm); group C, moderate atherosclerosis (1.2−1.8 mm); and group D, severe atherosclerosis (≥1.9 mm). EEG markers of power ratio index (PRI), and the binary likelihood of being in the VCI group vs. the that of being in control group A (sLx:VCI−A, vLx:VCI−A) were assessed, respectively. Differences in mean total scores for PRI, sLx:VCI−A, vLx:VCI−A, between control group A and the other groups were compared using Dunnett's test, respectively., Results: The mean total scores of the PRI were 3.25, 3.00, 2.77, and 2.26 for groups A, B, C, and D, respectively. There was a significant decrease in the PRI in group D compared with group A (P = 0.0066). The mean total scores of the sLx:VCI−A were −0.14, −0.11, −0.1, and −0.03 for groups A, B, C, and D, respectively. The sLx:VCI−A in group D was significantly higher compared to that in group A (P < 0.0001). The mean total scores of the vLx:VCI−A were −0.04,−0.01, 0.01, and 0.06 for group A, B, C, and D, respectively. The vLx:VCI−A in group D and group C was significantly higher compared to that in group A, respectively (P < 0.0001, P = 0.02)., Conclusion: Community-dwelling elderly subjects in the increased carotid atherosclerosis of ICA–IMT (≥1.9 mm) were at greatest risk of an EEG change as assessed by NAT.

Cognitive impairments are a core feature in schizophrenia patients (SCZ) and are also observed in first-degree relatives (FR) of SCZ. However, substantial variability in the impairments exists within and among SCZ, FR and healthy controls (HC). A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among SCZ, unaffected FR and HC. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (SCZ, FR and HC), cognitive clustering was performed, and differences in the BACS subscales among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. As expected, there were significant differences in the five BACS subscales among the diagnostic groups. The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal, (ii) intermediate impaired and (iii) widespread impaired. The cognitive subgroups were mainly affected by the clinical diagnosis, and significant differences in all BACS subscales among clusters were found. The effects of the diagnosis and cognitive clusters on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex (ACC) volumes were affected by the additive effects of diagnosis and cognition. Our findings demonstrate a cognitive continuum among SCZ, FR and HC and support the concept of cognitive impairment and the related ACC volumes as intermediate phenotypes in SCZ., Highlights • Cognitive impairments in the BACS subscales were a continuum among SCZ, FR and HC. • Cognitive clustering based on the BACS regardless of clinical diagnosis was performed. • Neuropsychologically normal, intermediately impaired and widespread impaired cognitive clusters were identified. • The cognitive clusters were mainly affected by the clinical diagnosis (SCZ, FR and HC). • Frontal and temporal volumes were mainly affected by the diagnosis. • The ACC volumes were affected by the additive effects of diagnosis and cognition.

Background The voice carries various information produced by vibrations of the vocal cords and the vocal tract. Though many studies have reported a relationship between vocal acoustic features and depression, including mel-frequency cepstrum coefficients (MFCCs) which applied to speech recognition, there have been few studies in which acoustic features allowed discrimination of patients with depressive disorder. Vocal acoustic features as biomarker of depression could make differential diagnosis of patients with depressive state. In order to achieve differential diagnosis of depression, in this preliminary study, we examined whether vocal acoustic features could allow discrimination between depressive patients and healthy controls. Methods Subjects were 36 patients who met the criteria for major depressive disorder and 36 healthy controls with no current or past psychiatric disorders. Voices of reading out digits before and after verbal fluency task were recorded. Voices were analyzed using OpenSMILE. The extracted acoustic features, including MFCCs, were used for group comparison and discriminant analysis between patients and controls. Results The second dimension of MFCC (MFCC 2) was significantly different between groups and allowed the discrimination between patients and controls with a sensitivity of 77.8% and a specificity of 86.1%. The difference in MFCC 2 between the two groups reflected an energy difference of frequency around 2000–3000 Hz. Conclusions The MFCC 2 was significantly different between depressive patients and controls. This feature could be a useful biomarker to detect major depressive disorder. Limitations Sample size was relatively small. Psychotropics could have a confounding effect on voice.

Over the last decade, research using positron emission tomography (PET) or single photon-emission computed tomography (SPECT) has revealed the distinguishing regional cerebral hypometabolism or hypoperfusion in various neurodegenerative disorders, which is useful for differential diagnosis of diseases. In addition to that, development of statistical analysis of neuroimaging data unveiled the subtle changes which was difficult to notice with visual inspection. SPECT findings of typical AD are characterized with hypoperfusion in (1) parietotemporal association cortex, (2) posterior cingulate gyrus and precuneus, and (3) medial temporal areas. Hypoperfusion in these regions might be a predictor for cognitive decline. With these findings, the neuroimaging examinations have become essential in clinical settings for the purpose of diagnosis of very early Alzheimer’s disease (AD) at a prodromal stage, prediction of conversion from mild cognitive impairment (MCI) to AD, or differential diagnosis from other diseases causing dementia.

Objectives It has been suggested that exercise improves cognitive function and increases cerebral volume even in older people. However, the relation between cognitive function and brain volume is unclear. We evaluated the longitudinal change of cognitive function and gray matter volume due to mild-intensity exercise over 2 years, and the residual effects 6 months post-exercise. Methods Subjects were 110 healthy older individuals over 65 years old in Tone town, Ibaraki prefecture. Seventy-five participants were voluntarily enrolled in the exercise group. A mild-intensity calisthenics regimen, which consisted of home-based and club-based programs for as long as 2 years, was employed as the intervention for the exercise group. Results The exercise group showed significant improvement in attentional shift over the course of the observation period including a 6-month follow-up. Neuroimaging analysis revealed the significant preservation of bilateral prefrontal volume in the exercise group with small-volume corrections, although this effect faded after intervention. Furthermore, the longitudinal changes in attentional shift and memory were positively correlated with the prefrontal volumetric changes. Conclusion Our results suggest that mild-intensity exercise could prevent prefrontal volume reduction due to aging and impede cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

Introduction: Although anxiety symptoms are often observed in Alzheimer's disease (AD), little attention has been paid to this symptom compared with other neuropsychiatric symptoms. Methods: Twenty-six patients with mild AD underwent both magnetic resonance imaging and single photon emission tomography with technetium-99m ethyl cysteinate dimer. Neuropsychiatric symptoms were evaluated using the Behavioral Pathology in Alzheimer's Disease Scale (Behave-AD). We investigated the relationship between anxiety and neuroimaging using Statistical Parametric Mapping 8 software. Results: The Behave-AD anxiety score was correlated with hyperperfusion in the bilateral anterior cingulate cortices and a reduction in the gray matter volume in the right precuneus and inferior parietal lobule. Conclusion: Our results suggest that anxiety in AD could overlap with the neural correlates of anxiety disorders, and that the specific degeneration associated with AD might be associated with anxiety.

To better understand the risk factors and optimal therapeutic strategies of cerebral white matter hyperintensity (WMH), we examined a large population of adults with and without various vascular risk factors (VRFs) or vascular risk conditions (VRCs), such as hypertension (HT), diabetes mellitus (DM), and dyslipidemia (DLP), including the comorbidities. We assessed two participant groups having no medical history of stroke or dementia that underwent brain checkup using magnetic resonance imaging (MRI): 5541 participants (2760 men, 2781 women) without VRCs and 1969 participants (1169 men, 800 women) who had received drug treatments for VRCs and the combination of comorbidities. For data analysis, we constructed WMH-brain healthcare quotient (WMH-BHQ) based on the percentile rank of WMH volume. This metric has an inverse relation to WMH. Multiple linear regression analysis of 5541 participants without VRCs revealed that age, systolic blood pressure (SBP), Brinkman index (BI), and female sex were significant factors lowering WMH-BHQ, whereas body mass index (BMI), male sex, fasting blood sugar, and triglyceride levels were increasing factors. The Kruskal&ndash, Wallis test and Dunn tests showed that WMH-BHQs significantly increased or decreased with BMI or SBP and with BI classification, respectively. Regarding the impact of impaired fasting glucose and abnormal lipid metabolism, there were almost no significant relationships. For 1969 participants who had HT, DM, and DLP, as well as their comorbidities, we found that DLP played a substantial role in increasing WMH-BHQ for some comorbidities, whereas the presence of HT and DM alone tended to decrease it. Cerebral WMH can be used as a healthcare quotient for quantitatively evaluating VRFs and VRCs and their comorbidities.

Neuromodulation therapies such as electroconvulsive therapy (ECT) are used to treat several neuropsychiatric disorders, including major depressive disorder (MDD). Recent work has highlighted the use of combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to evaluate the therapeutic effects of neuromodulation; particularly, the phase locking factor (PLF) and phase locking value (PLV) can reportedly assess neuromodulation-induced functional changes in cortical networks. To examine changes in TMS-induced PLV and PLF before and after ECT, and their relationship with depression severity in patients with MDD, TMS-EEG and the Montgomery–Åsberg Depression Rating Scale (MADRS; depression severity) were implemented before and after ECT in 10 patients with MDD. Single-pulse TMS was applied to the visual and motor areas to induce phase propagation in the visuo-motor network at rest. Functional changes were assessed using PLF and PLV data. Pre-ECT TMS-induced alpha band (9–12 Hz) PLV was negatively correlated with depression severity, and increments of post-ECT from pre-ECT TMS-induced alpha band PLV were positively correlated with the reduction in depression severity. Moreover, we found a negative correlation between pre-ECT TMS-induced PLF at TMS-destination and depression severity. Finally, differences in post-ECT TMS-induced PLF peak latencies between visual and motor areas were positively correlated with depression severity. TMS-EEG-based PLV and PLF may be used to assess the therapeutic effects of neuromodulation and depressive states, respectively. Furthermore, our results provide new insights about the neural mechanisms of ECT and depression.

Background: The loss of social support is one of the major risk factors for suicide. However, there are few empirical studies that have examined how a person’s suicide ideation relates to their social support. Aims: To examine the relationship between social support and suicidal ideation. Methods: Self-report questionnaires were sent to 2,200 randomly selected adults in Japan. The questionnaire inquired the participants about the severity of suicidal ideation, the details of current perceived social support and their degree of satisfaction with this social support. Social support and related indicators were compared among three groups of participants that varied in severity of suicidal ideation. Results: People in the group that had suicide ideation during their lives reported receiving significantly less support from their family and had greater feelings of dissatisfaction with that support than those in the other groups. Furthermore, people who had suicide ideation during the month immediately preceding the survey reported providing less support to their family, relatives or friends, as well as receiving less support from family than other groups, and having stronger feelings of dissatisfaction with social support. Conclusion: Our study identified a strong relationship between the severity of suicidal ideation and perceived social support.

Despite the fact that social anxiety disorder (SAD) is highly prevalent, there have been only a few structural imaging studies. Moreover, most of them reported about a volume reduction in amygdale, which plays a key role in the neural function of SAD. Insula is another region of interest. Its hyperactivity in regard to processing negative emotional information or interoceptive awareness has been detected in patients with SAD. Referring to these studies, we hypothesized that insular volumes might reduce in patients with SAD and made a comparison of insular volumes between 13 patients with SAD and 18 healthy controls with matched age and gender using voxel-based morphometry. As a result, we found a significant volume reduction in insula in the SAD group. Our results suggest that the patients with SAD might have an insular volume reduction apart from amygdala. Since insula plays a critical role in the pathology of SAD, more attention should be paid not only to functional study but also morphometrical study of insula.

Objective: Neuroimaging studies of bipolar disorders have provided an insight into the pathophysiology, and have raised an issue of a shared change with schizophrenia and the normalizing effect of lithium on the alteration. Despite the classification of the bipolar disorders into the bipolar I disorder (BP-I) and bipolar II disorder (BP-II), the patients with BP-II have only been involved in a limited number of the neuroimaging studies. There is minimal information about the direct comparison between BP-II and schizophrenia. Methods: All patients were diagnosed using DSM-5 criteria. A cross-sectional study was carried out to compare the regional brain volumes among the patients with BP-II taking lithium (BP-II-On, n=17) and not taking it (BP-II-Off, n=22), the patients with schizophrenia (n=35) and healthy controls (n=36). The MRI data were processed using Statistical Parametric Mapping 8 and the divided brain areas were defined by an automated anatomical labeling. Results: A significant reduction in the gray matter volume of the frontal, temporal and limbic lobes was similarly observed in BP-II-off and schizophrenia patients when compared to the controls. The brain volume of BP-II-On had significantly decreased in the temporal lobe, but not in either the frontal or limbic lobe. The less pronounced reduction of BP-II-On was also observed in the sub-regions of the prefrontal and limbic cortices, such as the anterior cingulate cortex. Conclusion: The present study suggests that there was a similarity in the distribution pattern of the decreased gray matter volume in the brain between BP-II and schizophrenia, placing an emphasis on the lithium effect that putatively normalized the abnormality in the anterior frontal and limbic brain areas of BP-II. However, further studies are required to replicate the results in a larger cohort and to confirm the lithium effect in a longitudinal study.

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.

BACKGROUND AND PURPOSE: The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. MATERIALS AND METHODS: A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage ( n = 45), mild stage ( n = 30) and moderate-to-advanced stages ( n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. RESULTS: Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. CONCLUSIONS: This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI.

Objective The ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux through the transfer of cholesterol from the inner to the outer layer of the cell membrane and regulates extracellular cholesterol levels in the central nervous system. Several lines of evidence have indicated lipid and myelin abnormalities in schizophrenia. Method Initially, we examined the possible association of the polymorphisms of the ABCA1 gene ( ABCA1 ) with susceptibility to schizophrenia in 506 patients with schizophrenia (DSM-IV) and 941 controls. The observed association was then subject to a replication analysis in an independent sample of 511 patients and 539 controls. We further examined the possible effect of the risk allele on gray matter volume assessed with magnetic resonance imaging (MRI) in 86 patients with schizophrenia (49 males) and 139 healthy controls (47 males). Results In the initial association study, the 1587 K allele (rs2230808) was significantly more common in male patients with schizophrenia than in male controls. Although such a significant difference was not observed in the second sample alone, the increased frequency of the 1587 K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587 K allele had a smaller amount of gray matter volume than those who did not carry the allele. Conclusion Our data suggest a male-specific association of the 1587 K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia.

Aim: The purpose of the present study was to investigate the regional cerebral blood flow (rCBF) of patients with delusional disorder, somatic type (DDST) exhibiting somatic hallucination. Methods: Five patients diagnosed with DDST, as well as 20 control subjects, were examined. All subjects underwent technetium-99m ethyl cysteinate dimer brain perfusion single-photon emission computed tomography. Statistical analysis was performed with SPM5, using a two-sample t-test model to test the regional population effect on rCBF. Results: Patients with DDST had a significant increase in perfusion in the left post-central gyrus and the right paracentral lobule, both of which are involved in somatic sensory processing. Conclusion: Somatic hallucination might be associated with increased perfusion in the primary somatosensory regions.

Background Cognitive impairments are a core feature in schizophrenia patients and are also observed in first-degree relatives of the schizophrenia patients. However, substantial variability in the impairments exists within and among schizophrenia patients, first-degree relatives and healthy controls. A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Methods Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among 81 schizophrenia patients, 20 unaffected first-degree relatives and 25 healthy controls. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (schizophrenia patients, first-degree relatives and healthy controls), cognitive clustering was performed using a k-means clustering analysis approach, and differences in the BACS subscales (verbal memory, digit sequencing, token motor, verbal fluency, symbol coding and Tower of London) among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. Results As expected, there were significant differences in the five BACS subscales among the diagnostic groups (verbal memory, F2,123=20.6, P=1.90 × 10–8; digit sequencing, F2,123=8.0, P=5.65 × 10–4; token motor, F2,123=16.0, P=6.92 × 10–7; verbal fluency, F2,123=14.8, P=1.79 × 10–6 and symbol coding, F2,123=28.8, P=5.64 × 10–11). The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal (Cluster 1, N=36), (ii) intermediate impaired (Cluster 2, N=60) and (iii) widespread impaired (Cluster 3, N=30). The cognitive subgroups were mainly affected by the clinical diagnosis (χ2=46.7, P=5.33 × 10-10), and significant differences in all BACS subscales among clusters were found (verbal memory, F2,123=64.1, P=8.49 × 10–20; digit sequencing, F2,123=35.7, P=5.89 × 10–13; token motor, F2,123=71.7, P=2.29 × 10–21; verbal fluency, F2,123=84.2, P=9.05 × 10–24; symbol coding, F2,123=115.6, P=5.70 × 10–29 and Tower of London, F2,123=6.9, P=1.43 × 10–3). The effects of the diagnosis (SCZ

Objectives Cerebral WMHs on T2-weighted magnetic resonance imaging (MRI) are common incidental findings in cognitively healthy elderly subjects. The relationship between such changes and cognitive function remains unclear. Methods The present study evaluated the relationship between the degree of white matter changes and cognitive function using data from 172 cognitively healthy subjects who underwent MRI and a battery of neuropsychological tests. The degree of WMHs was rated using a four-point scale for images on a computer screen. Results Regarding the frontal and parieto-occipital regions and basal ganglia region, compared with the group with no WMHs, the group with the most severe WMHs showed significantly lower performances for attention and disorientation to time, respectively. Conclusions Our results suggest that even in cognitively healthy elderly individuals, presence of large WMHs affects performance on certain cognitive domains according to their localization. Copyright © 2009 John Wiley & Sons, Ltd.

Background The results of previous reports estimating the prevalence of mild cognitive impairment (MCI) have varied widely according to the criteria used to define MCI. Methods We assessed the cognitive function of Japanese community-dwelling individuals ≥65 years old and attempted to estimate the prevalence of four MCI subtypes (amnestic single, amnestic multiple, nonamnestic single, and nonamnestic multiple) using two cutoffs (1 and 1.5 SD) below normative standard. Presence of apolipoprotein E4 allele (APOE4), which is known as a strong risk factor for AD, is reportedly associated with high risk of conversion from MCI to AD. We therefore calculated the frequency of APOE4 carriers for each MCI subtype. Results Initially 1888 (70%) of 2698 baseline samples participated, and 1433 (53%) subjects who had complete clinical data including APOE typing remained for the final analysis. The prevalence of MCI subtypes varied within the range of 1.7–16.6%, depending on the criteria applied. Prevalence of MCI was higher using a cutoff at −1.0 SD than at −1.5 SD, and prevalence of amnestic MCI single at −1.5 SD was lowest among all subtypes of MCI. Frequency of APOE4 was higher for amnestic MCI than for non-amnestic MCI or the cognitively normal group. Conclusion The prevalence of MCI was highly dependent on the diagnostic criteria applied. A higher frequency of APOE4 in participants with amnestic MCI subtype suggested a greater risk of future AD. For future interventions to delay the onset of dementia, targeting individuals with amnestic MCI multiple at −1 SD might be desirable. Copyright © 2009 John Wiley & Sons, Ltd.

Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional neuroimaging studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty‐two healthy subjects were studied (age 35.4 ± 12.1 years) using a 1.5‐T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel‐based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05). Right OFC GM volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results of this morphometry study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

Although the Internet has been widely used in Japan, the quality of information on mental health-related issues has not been evaluated so far. The purpose of the present study was to investigate the current status of Japanese websites that deal with mental health, mental disorders, and their associated matters. Using a search engine, Google, 37 websites were identified that exclusively contain information on mental health or mental disorders. The characteristics of the sites were then examined, along with variety of mental disorders mentioned, and quality of contents for each of the 37 websites. More than half of the websites were set up, at least in part, for commercial purposes and only 27% of sites were owned by professionals. Mood disorder, panic disorder, and schizophrenia were the three most commonly referred disorders on websites. Aside from some exceptions, the quality of information was inadequate, especially that regarding treatment. Most of the websites on mental health and mental disorders examined in the present study have scope for improvement. The challenge is to establish a system to evaluate the sites and to motivate each webmaster to improve the sites.