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Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.

In Japan, schizophrenia was renamed in 2002 to reduce the stigma that people with schizophrenia are dangerous. However there has been little research on the potential anti-stigma effect of renaming. The present study aimed to examine whether portrayals of schizophrenia in newspapers as dangerous have been varied across renaming of the disease. To achieve this goal, newspaper articles containing the previous and new Japanese names for schizophrenia, published in the decades before and after the renaming, were identified through the database of the three largest Japanese national broadsheets. Identified articles were divided into two categories: a negative category, including a subcategory “danger”; and a positive category. Articles containing bipolar disorder were adopted as a control. The ratio of the number of articles on schizophrenia and danger to that of bipolar disorder was analysed as a variable of interest. The trend of this ratio was investigated to examine whether portrayals of schizophrenia changed after renaming. The search identified 4677 articles on schizophrenia, 53.0% of which were categorised as negative and 38.9% as danger. The search identified 525 articles on bipolar disorder, 24.6% of which were categorised as negative and 11.2% as danger. There was an increase of the ratio before schizophrenia was renamed (r = 0.54, p = 0.104), and a significant decrease after renaming (r = − 0.69, p = 0.028). Fisher's r-to-z transformation demonstrated a significant change in the trend of the ratio across renaming (Z = 2.72, p = 0.007). Renaming schizophrenia might be associated with mitigation in potentially stigmatised depiction of schizophrenia associated with violence in newspaper reports.

AIM Auditory mismatch negativity (MMN) and its magnetoencephalographic (MEG) counterpart (MMNm) are an established biological index in schizophrenia research. MMN in response to duration and frequency deviants may have differential relevance to the pathophysiology and clinical stages of schizophrenia. MEG has advantage in that it almost purely detects MMNm arising from the auditory cortex. However, few previous MEG studies on schizophrenia have simultaneously assessed MMNm in response to duration and frequency deviants or examined the effect of chronicity on the group difference. METHODS Forty-two patients with chronic schizophrenia and 74 matched control subjects participated in the study. Using a whole-head MEG, MMNm in response to duration and frequency deviants of tones was recorded while participants passively listened to an auditory sequence. RESULTS Compared to healthy subjects, patients with schizophrenia exhibited significantly reduced powers of MMNm in response to duration deviant in both hemispheres, whereas MMNm in response to frequency deviant did not differ between the two groups. These results did not change according to the chronicity of the illness. CONCLUSION These results, obtained by using a sequence-enabling simultaneous assessment of both types of MMNm, suggest that MEG recording of MMN in response to duration deviant may be a more sensitive biological marker of schizophrenia than MMN in response to frequency deviant. Our findings represent an important first step towards establishment of MMN as a biomarker for schizophrenia in real-world clinical psychiatry settings.

AIM: Go/No-go derived event-related potential (ERP) signals have been widely used in schizophrenia research to monitor self-control deficits in this disorder. However, no study to date has associated Go/No-go related ERPs with global functioning. METHODS: Participants consisted of 21 patients with schizophrenia and 22 healthy controls. We used a visual Go/No-go paradigm to measure Go/No-go-related N2/P3 ERP components by means of a 64-electrode cap for EEG recording. We used the Global Assessment of Functioning (GAF) to evaluate global functioning and analyzed the correlation between ERP indices and global functioning scores. RESULTS: N2 amplitudes were reduced in patients with schizophrenia, but not influenced by either Go/No-go condition. P3 amplitudes were influenced by the Go/No-go conditions, but not reduced in patients with schizophrenia. Global functioning was correlated with the No-go P3 amplitudes, but not N2 amplitudes, in patients with schizophrenia. CONCLUSION: These results indicate that global functioning is associated with intact neural activity rather than impaired neural activity during Go/No-go response inhibition tasks in patients with schizophrenia.This article is protected by copyright. All rights reserved. Language: en

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum., Autism spectrum disorder (ASD) is manifested by subtle but significant changes in the brain. Here, Yahata and colleagues devise a novel machine learning algorithm and develop a reliable ASD classifier based on brain functional connectivity, with which they quantitatively measure neuroimaging dimensions between ASD and other mental disorders.

Background Few biomarkers can be used easily and noninvasively to measure clinical condition and future outcome in patients with first-episode psychosis (FEP). To develop such biomarker using multichannel functional near-infrared spectroscopy (fNIRS), cortical function in the prefrontal cortex was longitudinally measured during a verbal fluency task. Methods Sixty-nine fNIRS measurements and 77 clinical assessments were obtained from 31 patients with FEP at baseline, 6-month, and 12-month follow-ups. Sixty measurements were obtained from 30 healthy controls matched for age, sex, and premorbid IQ. We initially tested signal changes for 12 months, and then investigated the relationship between fNIRS signals and clinical assessments. Results Signal changes from baseline to 12-month follow-up were not evident in any group. Patients with FEP had significant positive correlation coefficients between 6-month fNIRS signals and the 12-month Global Assessment of Functioning (GAF) score in the left middle frontal gyrus (FDR-corrected p = .0016–.0052, r = .65–.59). fNIRS signals at the 12-month follow-up were associated with 12-month GAF score in the bilateral superior and middle frontal gyri (FDR-corrected p = .00085–.018, r = .72–.55), and with the difference between baseline and 12-month GAF scores in the right superior frontal gyrus (FDR-corrected p = .000067–.00012, r = .80–.78). These associations were significant even after controlling for demographic variables. No association between baseline fNIRS signals and later GAF scores was found. Discussion fNIRS measurement can potentially be used as a biomarker to aid sequential assessment of neuro-clinical conditions through the early stage of psychosis.

© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Abstract. Hippocampus volume has been frequently, but not universally reported to be reduced in people with major depression relative to age-matched healthy controls. Among the potential reasons for this discrepancy in finding across studies is the effect of antidepressant medication. Hippocampus volume was determined by MRI (1.5 Tesla) for 10 people diagnosed with major depression for who detailed history of depression and antidepressant treatment history were known, and 10 age-matched healthy controls with no history of depression. Left, but not right, hippocampus volumes were significantly smaller in the patient group compared to the controls. Furthermore, there was a significant correlation such that left hippocampus volume was smaller with increasing lifetime duration of depression. However, this relationship was moderated by a significant correlation such that greater lifetime duration of antidepressant medication was associated with larger left hippocampus volume. The findings support the contention that antidepressant medication may act to normalize hippocampus volume.

Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to tone duration changes, tone frequency changes, and phonemic changes was recorded using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs underwent blood sampling for determination of plasma amino acid levels. MMNm peak strength showed relatively high correlations in both MZ and DZ twin pairs. The differences in MMNm latencies tended to correlate with the differences in plasma amino acid levels within MZ pairs, while no significant correlation was observed after the Bonferroni correction. We observed a familial trait in MMNm strength. The differences in MMN latency in MZ twins might be influenced by changes in glutamate levels and glutamate-glutamine cycling; however, the results need to be replicated.

Background Premature death in individuals with severe mental illness (SMI) in countries without nationally collected data, including Japan, is structurally underreported. Aims To elucidate excess mortality among individuals with SMI in Japan. Method We retrospectively investigated all deaths among users of a non-clinical community-based mental health service provider in suburban Tokyo from 1992 to 2015. Results During the study period, 45 individuals died among 254 qualified registrants. Deaths were by natural causes in 33 cases (73.3%). The mean years of life lost was 22.2 years and the overall standard mortality ratio (SMR) was 3.28 (95% CI 2.40–4.39). The cause-specific SMR was 5.09 (95% CI 2.33–9.66) for cardiovascular disease and 7.38 (95% CI 2.40–17.22) for suicide. Conclusions Although Japan leads the world in longevity, individuals with SMI suffer premature death and excess mortality due to physical conditions as well as suicide. Revealing this underreported disparity of life is the first step to improving physical care for individuals with SMI. Declaration of interest S.K. received personal fees from Pfizer and Dainippon-Sumitomo, outside the submitted work, and was a medical adviser to Sudachi-kai. Y.K. received grants from Japan Foundation for Neuroscience and Mental Health (JFNMH), during the conduct of the study, and personal fees from Dainippon-Sumitomo, outside the submitted work. K.K. received grants from Japan Society for the Promotion of Science (JSPS) and Japan Agency for Medical Research and Development (AMED), during the conduct of the study; personal fees from Daiichi-Sankyo, Otsuka, Meiji-Seika Pharma, Yoshitomi, Mochida and Fuji-Film RI Pharma; grants and personal fees from MSD, Astellas, Dainippon-Sumitomo and Eisai; and grants from Lily, Takeda and Tanabe-Mitsubishi, outside the submitted work. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Sleep problems during adolescence affect current and subsequent mental health and are associated with experiences of psychotic symptoms. Recent studies have suggested that short sleep duration increases the risk of experiencing psychotic symptoms in the general adolescent population; however, whether long sleep duration is associated with an increased risk of psychotic symptoms in adolescence remains unclear. The present study aimed to examine the relationships between long sleep duration, short sleep duration, and the risk of experiencing psychotic symptoms in adolescence. Cross-sectional survey data from 15,786 junior and senior high school students (12- to 15-year-olds and 15- to 18-year-olds, respectively) in Japan were collected and analyzed using logistic regression analysis after controlling for covariates, including depressive symptoms. Long sleep duration was associated with a 1.6- to 2.8-fold increased risk of psychotic symptoms in male but not in female adolescents. Short sleep duration was also related with a 1.6- to 2.9-fold increased risk of experiencing psychotic symptoms, except for 15- to 18-year-old female adolescents. The present study suggested that adolescents with long and short sleep duration should be assessed for their risk of experiencing psychotic symptoms regardless of concurrent depressive symptoms.

Maternal breastfeeding has an impact on motor and emotional development in children of the next generation. Elucidating how breastfeeding during infancy affects brain regional structural development in early adolescence will be helpful for promoting healthy development. However, previous studies that have shown relationships between breastfeeding during infancy and cortical brain regions in adolescence are usually based on maternal retrospective recall of breastfeeding, and the accuracy of the data is unclear. In this study, we investigated the association between breastfeeding duration and brain regional volume in a population-neuroimaging study of early adolescents in Japan (N ​= ​207; 10.5–13.4 years) using voxel-based morphometry, which enabled us to analyze the whole brain. We evaluated breastfeeding duration as indexed by maternal and child health handbook records during infancy. The results showed a significant positive correlation between the duration of breastfeeding and gray matter volume in the dorsal and ventral striatum and the medial orbital gyrus. Post hoc exploratory analyses revealed that the duration of breastfeeding was significantly correlated with emotional behavior. Additionally, the volume in the medial orbital gyrus mediated an association between breastfeeding duration and emotional behavior. This is the first study to evaluate the effect of breastfeeding during infancy on regional brain volumes in early adolescence based on maternal and child health handbook records. Our findings shed light upon the importance of maternal breastfeeding for brain development related to emotional and motivational processing in early adolescence.

Parent-child personality transmission can occur via biological gene-driven processes as well as through environmental factors such as shared environment and parenting style. We recently revealed a negative association between prosociality, a highly valued personality attribute in human society, and anterior cingulate cortex (ACC) γ-aminobutyric acid (GABA) levels in children at the age of 10 years. We thus hypothesized that prosociality would be intergenerationally transmitted, and that transmission would be underwritten by neurometabolic heritability. Here, we collected prosociality data from children aged 10 years and their parents in a large-scale population-based birth cohort study. We also measured ACC GABA+ and glutamate plus glutamine (Glx) levels in a follow-up assessment with a subsample of the participants (aged 11 years) using magnetic resonance spectroscopy. We analyzed the associations among children’s and parents’ prosociality and GABA+/Glx ratios. We also examined the effect of socioeconomic status (SES) and verbalized parental affection (VPA) on these associations. We found a significant positive parent-child association for prosociality (N ​= ​3026; children’s mean age 10.2 years) and GABA+/Glx ratio (N ​= ​99; children’s mean age 11.4 years). There was a significant negative association between GABA+/Glx ratio and prosociality in both children (N ​= ​208) and parents (N ​= ​128). Our model accounting for the effects of neurometabolic heritability on prosociality transmission fitted well. Moreover, in this model, a significant positive effect of VPA but not SES on children’s prosociality was observed independently of the effect of neurometabolic transmission, while SES but not VPA was significantly associated with parental prosociality. Our results provide novel insights into the neurometabolic substrates of parent-child transmission of social behavior.

Accumulating evidence suggests that aberrant epigenetic regulation is involved in the pathophysiology of major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). We previously showed that the plasma level of betaine (N,N,N-trimethylglycine), a methyl-group donor, was significantly decreased in patients with first episode schizophrenia (FESZ). In this study, we identified decrease of global DNA methylation level in FESZ (N = 24 patients vs N = 42 controls), and found that global DNA methylation level was inversely correlated with scores on the global assessment of functioning (GAF) scale, and positively correlated with plasma betaine level. Notably, correlations between levels of betaine and its metabolites (N,N-dimethylglycine and sarcosine, N-methylglycine) were lower or lost in FESZ plasma, but remained high in controls. We further examined global DNA methylation levels in patients with chronic SZ (N = 388) and BD (N = 414) as well as controls (N = 430), and confirmed significant hypomethylation and decreased betaine level in SZ. We also found that patients with BD type I, but not those with BD type II, showed significant global hypomethylation. These results suggest that global hypomethylation associated with decreased betaine level in blood cells is common to SZ and BD, and may reflect common pathophysiology such as psychotic symptoms.

Early-maturing girls are relatively likely to experience compromised psychobehavioral outcomes. Some studies have explored the association between puberty and brain morphology in adolescents, while the results were non-specific for females or the method was a region-of-interest analysis. To our knowledge, no large-scale study has comprehensively explored the effects of pubertal timing on whole-brain volumetric development or the neuroanatomical substrates of the association in girls between pubertal timing and psychobehavioral outcomes. We collected structural magnetic resonance imaging (MRI) data of a subsample (N ​= ​203, mean age 11.6 years) from a large-scale population-based birth cohort. Tanner stage, a scale of physical maturation in adolescents, was rated almost simultaneously with MRI scan. The Strengths and Difficulties Questionnaire total difficulties (SDQ-TD) scores were rated by primary parents some duration after MRI scan (mean age 12.1 years). In each sex group, we examined brain regions associated with Tanner stage using whole-brain analysis controlling for chronological age, followed by an exploration of brain regions also associated with the SDQ-TD scores. We also performed mediation analyses. In girls, Tanner stage was significantly negatively correlated with gray matter volumes (GMVs) in the anterior/middle cingulate cortex (ACC/MCC), of which the subgenual ACC (sgACC) showed a negative correlation between GMVs and SDQ-TD scores. Smaller GMVs in the sgACC mediated the association between higher Tanner stages and higher SDQ-TD scores. We found no significant results in boys. Our results from a minimally biased, large-scale sample provide new insights into neuroanatomical correlates of the effect of pubertal timing on developmental psychological difficulties emerging in adolescence.

Background Supporting personal recovery in people with mental health difficulties is central to mental health services. This study aimed to develop the Japanese version of INSPIRE and Brief INSPIRE measure of staff support for personal recovery and to evaluate its reliability and validity. Methods A questionnaire survey was conducted from October to December 2015. The authors asked users to participate in the survey of 14 community mental health services in the Kanto region of Japan. The service users completed self-administered questionnaires that include the Japanese version of INSPIRE, the Recovery Assessment Scale, the Client Satisfaction Questionnaire, the patient version of the Scale to Assess Therapeutic Relationship in Community Mental Health care and the Short Form Health Survey. Internal consistency was assessed using Cronbach’s alpha coefficient, and test-retest reliability was assessed using the intraclass correlation coefficient (ICC) and weighted kappa. Convergent validity was examined by assessing correlation with other scales. Factor validity was evaluated by exploratory factor analysis (EFA) with generalized least-squares mean and oblimin rotation. In addition, confirmatory factor analysis was used to check the fitness of the factor structure models derived from the EFA. Results A total of 195 out of 212 users gave written informed consent and participated in the study. Data from 190 respondents were analyzed (response rate 89.6%). INSPIRE, Brief INSPIRE, and the subscales all showed Cronbach’s alpha coefficient over 0.78. ICC and weighted kappa derived more than 0.92 for subscales and Brief INSPIRE. These numerical values indicated good reliability. The convergent validity of Brief INSPIRE and the subscales was significantly positively correlated with the other scales. Different from the previous study, the factor structure was extracted using EFA. Both factor structures were checked by CFA, but the degree of fitness index was not good in either. Therefore, the factor analysis did not show goodness of fit. Conclusions This study found the Japanese version of INSPIRE and Brief INSPIRE to be reliable and valid for use among community mental health service users in Japan.

Personal recovery is increasingly recognised as an important outcome measure in mental health services. This study aimed to develop a Japanese version of the Questionnaire about the Process of Recovery (QPR-J) and test its validity and reliability.The study comprised two stages that employed the cross-sectional and prospective cohort designs, respectively. We translated the questionnaire using a standard translation/back-translation method. Convergent validity was examined by calculating Pearson's correlation coefficients with scores on the Recovery Assessment Scale (RAS) and the Short-Form-8 Health Survey (SF-8). An exploratory factor analysis (EFA) was conducted to examine factorial validity. We used intraclass correlation and Cronbach's alpha to examine the test-retest and internal consistency reliability of the QPR-J's 22-item full scale, 17-item intrapersonal and 5-item interpersonal subscales. We conducted an EFA along with a confirmatory factor analysis (CFA).Data were obtained from 197 users of mental health services (mean age: 42.0 years; 61.9% female; 49.2% diagnosed with schizophrenia). The QPR-J showed adequate convergent validity, exhibiting significant, positive correlations with the RAS and SF-8 scores. The QPR-J's full version, subscales, showed excellent test-retest and internal consistency reliability, with the exception of acceptable but relatively low internal consistency reliability for the interpersonal subscale. Based on the results of the CFA and EFA, we adopted the factor structure extracted from the original 2-factor model based on the present CFA.The QPR-J is an adequately valid and reliable measure of the process of recovery among Japanese users with mental health services.

Aim Utena's Brief Objective Measures (UBOM) was developed to assess psychophysiological functions proximal to real-world functioning in individuals with psychiatric disorders, including schizophrenia (SCZ), to facilitate shared decision-making. However, the validity of UBOM has not been fully examined. Methods We conducted a cross-sectional observational study to evaluate the validity of each of the three tests in UBOM: UBOM-Pulse, UBOM-Ruler, and UBOM-Random. We investigated associations: (i) between UBOM and existing cognitive- and autonomic-function tests; and (ii) between UBOM and daily social functioning. The participants included SCZ individuals and healthy controls. We evaluated the cognitive and autonomic function using UBOM, the heart rate variability test, the simple reaction time test, and the Brief Assessment of Cognition in Schizophrenia, Japanese version. We also assessed the daily social functioning using the WHO Disability Assessment Schedule 2.0 and the modified Global Assessment of Functioning, Japanese version. Results Thirty-one SCZ individuals and 35 healthy control individuals participated in this study. In the SCZ group, UBOM-Ruler was significantly associated with the Cognition and Getting Along domains of WHO Disability Assessment Schedule 2.0. UBOM-Random was significantly associated with the Brief Assessment of Cognition in Schizophrenia's Working Memory, Verbal Fluency and Attention domains, and the modified Global Assessment of Functioning in the SCZ group. Conclusion The validity of the current version of UBOM is imperfect and further improvements will be necessary to attain the originally intended goal of developing a brief assessment tool for real-world functioning in SCZ.

The Portrait Values Questionnaire (PVQ) is a widely used questionnaire for assessing sense of values; however, it has limitations, especially for children. Therefore, the present study aims to develop a questionnaire for sense of values, called the Brief Personal Values Inventory (BPVI), consisting of simple questions and a smaller number of items compared to the PVQ. We first created 12 items for the BPVI and then tested their validity and reliability in 167 Japanese general population (81 males, mean age (SD) [range]: 23.4 (8.2) [15-57] years). Each of these items was correlated with one or more values in the PVQ-57. The BPVI items covered all higher-order values in Schwartz’s theory (Openness to Change, Self-Enhancement, Conservation, and Self-Transcendence). In sum, the BPVI has an acceptable criterion-related validity and corresponds to higher-order values in Schwartz’s value theory. The BPVI is suitable for a reliable and direct comparison of sense of values between children and adults, which may be useful for elucidating the developmental pathway of personal sense of values.

Subcortical structures may have an important role in the pathophysiology of psychosis. Our recent mega-analysis of structural magnetic resonance imaging (MRI) data has reported subcortical volumetric and lateralization alterations in chronic schizophrenia, including leftward asymmetric increases in pallidal volume. The question remains, however, whether these characteristics may represent vulnerability to the development of psychosis or whether they are epiphenomena caused by exposure to medication or illness chronicity. Subclinical psychotic experiences (SPEs) occur in some adolescents in the general population and increase the odds of developing psychosis in young adulthood. Investigations into the association between SPEs and MRI-measured volumes of subcortical structures in the general adolescent population would clarify the issue. Here, we collected structural MRI data in a subsample (10.5–13.3 years old) of a large-scale population-based cohort and explored subcortical volume and lateralization alterations related to SPEs (N = 203). Adolescents with SPEs demonstrated significant volumetric increases in the left hippocampus, right caudate, and right lateral ventricle, as well as a marginally significant increase in the left pallidum. Furthermore, adolescents with SPEs showed significantly more leftward laterality of pallidal volume than individuals without SPEs, which replicates our mega-analysis findings in chronic schizophrenia. We suggest that leftward asymmetries in pallidal volume already present in early adolescence may underlie the premorbid predisposition for developing psychosis in later life.

The auditory steady-state response (ASSR) has been used to detect auditory processing deficits in patients with psychiatric disorders. However, the methodology of ASSR recording from the brain surface has not been standardized in preclinical studies, limiting its use as a translational biomarker. The sites of maximal ASSR in humans are the vertex and/or middle frontal area, although it has been suggested that the auditory cortex is the source of the ASSR. We constructed and validated novel methods for ASSR recording using a switchable pedestal which allows ASSR recording alternatively from temporal or parietal cortex with a wide range of frequencies in freely moving rats. We further evaluated ASSR as a translational tool by assessing the effect of ketamine. The ASSR measured at parietal cortex did not show clear event-related spectral perturbation (ERSP) or inter-trial coherence (ITC) in any frequency bands or a change with ketamine. In contrast, the ASSR at temporal cortex showed clear ERSP and ITC where 40 Hz was maximal in both gamma-band frequencies. Ketamine exerted a biphasic effect in ERSP at gamma bands. These findings suggest that temporal cortex recording with a wide frequency range is a robust methodology to detect ASSR, potentially enabling application as a translational biomarker in psychiatric and developmental disorders.

Mismatch negativity (MMN) reduction is one of the most robust findings among several neurophysiological and neurocognitive measures in patients with schizophrenia. MMN is a promising biomarker for schizophrenia because of the following properties: 1) its relationship with early psychosis, including clinical high-risk (CHR); 2) its relationship with the functional abilities of patients; and 3) its translatability into basic research using animal models. Specifically, the utility of the passive auditory oddball paradigm that does not require subjects to make behavioral responses enables identical physiological activities to be obtained from both experimental animals and patients. This advantage has contributed to clarifying the generating mechanism of MMN in various animal studies. We reviewed clinical reports focused on early psychosis; specifically differential effects of deviance type and relationships to clinical and functional outcome. For the utility of MMN as a tool for translational research, we next reviewed recent MMN studies in rodents and nonhuman primates (NHP) as well as studies using intracranial recordings in humans, a rare opportunity to detect neural signals in vivo in humans. Neural computations of MMN, such as adaptation, deviance detection, and predictive coding, have been recent topics for understanding MMN generating mechanisms. Finally, several significant research questions were provided for future directions. MMN research could contribute to innovative, novel, therapeutic strategies in the future by becoming a bridge between basic and clinical research.

Previous studies have shown glutamatergic dysfunction and γ-aminobutyric acid (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with each other and lead to alterations in excitatory/inhibitory balance. The NMDAR and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN) and auditory steady-state gamma-band response (ASSR), respectively. However, no previous studies have tested the hypothesis of an abnormal association between MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of NMDAR-GABA association during the early stages of psychosis. Participants were individuals with recent-onset schizophrenia (ROSZ; N = 21), ultra-high risk (UHR; N = 27), and healthy controls (HCs; N = 24). The MMN amplitude was significantly impaired in ROSZ (p = 0.001, d = 1.20) and UHR (p = 0.003, d = 1.01) compared with HCs. The intertrial phase coherence (ITC) index of gamma-band ASSR was significantly reduced in ROSZ compared with HCs (p d = –1.27) and UHR (p = 0.032, d = –0.75). The event-related spectral perturbation (ERSP) index of gamma-band ASSR was significantly smaller in ROSZ compared with HCs (p d = −1.21). The MMN amplitude was significantly correlated with the ITC in ROSZ (r = −0.69, p

(Abstract included 248 words)Although the relationship between schizophrenia spectrum disorder (SSD) and autism spectrum disorder (ASD) has long been debated, it has not yet been fully elucidated. To address this issue, we took advantage of dual (ASD and SSD) classifiers that discriminate patients from their controls based on resting state brain functional connectivity. An SSD classifier using sophisticated machine-learning algorithms that automatically selected SSD- specific functional connections was applied to Japanese datasets including adult patients with SSD in a chronic stage. We demonstrated good performance of the SSD classification for independent validation cohorts. The generalizability was tested by USA and European cohorts in a chronic stage, and one USA cohort including first episode schizophrenia. The specificity was tested by two adult Japanese cohorts of ASD and major depressive disorder, and one European cohort of attention-deficit hyperactivity disorder. The weighted linear summation of the classifier’s functional connections constituted the biological dimensions representing neural liability to the disorders. Our previously developed robust ASD classifier constituted the ASD dimension. Distributions of individuals with SSD, ASD and healthy controls were examined on the SSD and ASD biological dimensions. The SSD and ASD populations exhibited overlapping but asymmetrical patterns on the two biological dimensions. That is, the SSD population showed increased liability on the ASD dimension, but not vice versa. Furthermore, the two dimensions were correlated within the ASD population but not the SSD population. Using the two biological dimensions based on resting-state functional connectivity enabled us to quantify and visualize the relationships between SSD and ASD.

BACKGROUND: Previous randomized controlled trials (RCTs) have shown a significant intervention effect of internet-based computerized cognitive behavioral therapy (iCBT) on improving nonclinical depressive symptoms among healthy workers and community residents in a primary prevention setting. Time preference is one's relative valuation for having a reward (eg, money) at present than at a later date. Time preference may affect the effectiveness of cognitive behavioral therapy.OBJECTIVE: This RCT aimed to test the difference of intervention effect of an iCBT program on improving nonclinical depressive symptoms between two subgroups classified post-hoc on the basis of time preference among workers in Japan.METHODS: All workers in one corporate group (approximate n=20,000) were recruited. Participants who fulfilled the inclusion criteria were randomly allocated to either intervention or control groups. Participants in the intervention group completed 6 weekly lessons and homework assignments within the iCBT program. The Beck Depression Inventory-II (BDI-II) and Kessler's Psychological Distress Scale (K6) measures were obtained at baseline and 3-, 6-, and 12-month follow-ups. Two subgroups were defined by the median of time preference score at baseline.RESULTS: Only few (835/20,000, 4.2%) workers completed the baseline survey. Of the 835 participants, 706 who fulfilled the inclusion criteria were randomly allocated to the intervention or control group. Participants who selected irrational time preference options were excluded (21 and 18 participants in the intervention and control groups, respectively). A three-way interaction (group [intervention/control] × time [baseline/follow-up] × time preference [higher/lower]) effect of iCBT was significant for BDI-II (t1147.42=2.33, P=.02) and K6 (t1254.04=2.51, P=.01) at the 3-month follow-up, with a greater effect of the iCBT in the group with higher time preference. No significant three-way interaction was found at the 6- and 12-month follow-ups.CONCLUSIONS: The effects of the iCBT were greater for the group with higher time preference at the shorter follow-up, but it was leveled off later. Workers with higher time preference may change their cognition or behavior more quickly, but these changes may not persist.TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000014146; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000016466 (Archived by WebCite at http://www.webcitation.org/70o2rNk2V).

Auditory contextual processing has been assumed to be based on a hierarchical structure consisting of the primary auditory cortex, superior temporal gyrus (STG), and frontal lobe. Recent invasive studies on mismatch negativity (MMN) have revealed functional segregation for auditory contextual processing such as neural adaptation in the primary auditory cortex and prediction in the frontal lobe. However, the role of the STG remains unclear. We obtained induced activity in the high gamma band as mismatch response (MMR), an electrocorticographic (ECoG) counterpart to scalp MMN, and the components of MMR by analyzing ECoG data from patients with refractory epilepsy in an auditory oddball task paradigm. We found that MMR localized mainly in the bilateral posterior STGs, and that deviance detection largely accounted for MMR. Furthermore, adaptation was identified in a limited number of electrodes on the superior temporal plane. Our findings reveal a mixed contribution of deviance detection and adaptation depending on location in the STG. Such spatial considerations could lead to further understanding of the pathophysiology of relevant psychiatric disorders.

This study investigated how the course of a mental illness is distributed and evaluated the risk factors and suicidality of chronic and delayed onset mental illness after the Great East Japan Earthquake. The first, second, and third waves of this study were conducted in 2012, 2013, and 2014, respectively. Psychological distress, suicidal ideation, and socio-demographics were assessed by a self-report questionnaire for affected residents (N = 1473; 768 females, 52.1%; average age = 66.3 years, ranged from 20 to 89 years). Prevalence of mental illness was 10.0%, 14.7%, and 11.8% in the first, second, and third waves, respectively. Prevalence of mental illness for three years was found to be 21.4% and of remission, chronic, and delayed-onset course was 5.0% (2.9–7.1%), 3.6% (1.6–5.8%), and 6.2% (4.2–8.4%), respectively. Psychological distress and serious damage to their homes in the first wave predicted chronic course. Psychological distress in the first wave, living at temporary housing, and unemployment in the third wave increased risk for delayed onset. Among the participants, 9.8% reported suicidal ideation. Chronic or delayed onset course showed a higher risk of suicidal ideation. Many residents, who showed high risk of suicidality, still suffer from mental illness requiring housing, occupation, and psychological support.

Eye movement abnormalities have been reported in schizophrenia; however, their influences on everyday life remain unknown. From data on 69 subjects with schizophrenia and 246 healthy subjects, we found positive correlations between eye movement measures and work hours, which were only significant in subjects with schizophrenia. This relationship was also confirmed in a multi-site dataset including 118 subjects with schizophrenia and 280 healthy subjects. These findings further strengthen our understanding of eye movement abnormalities and their relevance in clinical recovery.

Increasingly, national governments across the globe are prioritizing investments in neuroscience. Currently, seven active or in-development national-level brain research initiatives exist, spanning four continents. Engaging with the underlying values and ethical concerns that drive brain research across cultural and continental divides is critical to future research. Culture influences what kinds of science are supported and where science can be conducted through ethical frameworks and evaluations of risk. Neuroscientists and philosophers alike have found themselves together encountering perennial questions; these questions are engaged by the field of neuroethics, related to understanding of the nature of the self and identity, the existence and meaning of free will, defining the role of reason in human behavior, and more. With this Perspective article, we aim to prioritize and advance to the foreground a list of neuroethics questions for neuroscientists operating in the context of these international brain initiatives.

Aim Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence. Methods Participants in the first wave of the pn-TTC (pn-TTC-1) study were recruited from those of the TTC study, a large-scale epidemiological survey in which 3171 parent-adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting-state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn-TTC-2) followed similar methods as in the first wave. Results A total of 301 parent-adolescent pairs participated in the pn-TTC-1 study. Moreover, 281 adolescents participated in the pn-TTC-2 study, 238 of whom were recruited from the pn-TTC-1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html. Conclusion The pn-TTC project is a large-scale and population-neuroscience-based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience.

Objectives The rising prevalence of tobacco use and tobacco-attributable deaths among women is of worldwide concern. In particular, smoking prevention for mothers in early midlife is a significant international public health goal. A higher sense of purpose in life (PIL) is thought to reduce detrimental health behaviours. However, little is known about the association between a sense of PIL and tobacco use. This study investigates this association among community-dwelling mothers of early adolescents. Design This population-based cross-sectional study uses a self-reported questionnaire from the Tokyo Early Adolescence Survey, a large community-based survey conducted in Japan between 2012 and 2015. Setting Participants were randomly recruited from the resident registries of three municipalities in Tokyo, Japan. Participants A total of 4478 children and their primary parents participated. Responses from 4063 mothers with no missing data were analysed (mean age=42.0 years (SD=4.2)). Measures Participants’ tobacco use, including the number of cigarettes smoked per day, was documented using a questionnaire. PIL was assessed using a Purpose in Life scale derived from Ryff’s Psychological Well-Being Scale. Results Greater PIL was associated with a decreased likelihood of tobacco use, even when adjusted for confounders (OR=0.80, 95% CI 0.70 to 0.91). Multinomial logistic regression analyses revealed that PIL was inversely associated with tobacco consumption among mothers. These associations remained after controlling for psychological distress, socioeconomic factors and frequency of alcohol consumption among moderate to heavy smokers (OR=0.70, 95% CI 0.57 to 0.86), while attenuated among light smokers. Conclusions Increasing PIL may be a valuable intervention for reducing tobacco use among women in early midlife. This study can contribute to our understanding of the psychology of smoking behaviour and shed light on the targeted intervention to reduce tobacco use among early midlife mothers.

BACKGROUND Previous randomized controlled trials (RCTs) have shown a significant intervention effect of internet-based computerized cognitive behavioral therapy (iCBT) on improving nonclinical depressive symptoms among healthy workers and community residents in a primary prevention setting. Time preference is one’s relative valuation for having a reward (eg, money) at present than at a later date. Time preference may affect the effectiveness of cognitive behavioral therapy. OBJECTIVE This RCT aimed to test the difference of intervention effect of an iCBT program on improving nonclinical depressive symptoms between two subgroups classified post-hoc on the basis of time preference among workers in Japan. METHODS All workers in one corporate group (approximate n=20,000) were recruited. Participants who fulfilled the inclusion criteria were randomly allocated to either intervention or control groups. Participants in the intervention group completed 6 weekly lessons and homework assignments within the iCBT program. The Beck Depression Inventory-II (BDI-II) and Kessler’s Psychological Distress Scale (K6) measures were obtained at baseline and 3-, 6-, and 12-month follow-ups. Two subgroups were defined by the median of time preference score at baseline. RESULTS Only few (835/20,000, 4.2%) workers completed the baseline survey. Of the 835 participants, 706 who fulfilled the inclusion criteria were randomly allocated to the intervention or control group. Participants who selected irrational time preference options were excluded (21 and 18 participants in the intervention and control groups, respectively). A three-way interaction (group [intervention/control] × time [baseline/follow-up] × time preference [higher/lower]) effect of iCBT was significant for BDI-II (t1147.42=2.33, P=.02) and K6 (t1254.04=2.51, P=.01) at the 3-month follow-up, with a greater effect of the iCBT in the group with higher time preference. No significant three-way interaction was found at the 6- and 12-month follow-ups. CONCLUSIONS The effects of the iCBT were greater for the group with higher time preference at the shorter follow-up, but it was leveled off later. Workers with higher time preference may change their cognition or behavior more quickly, but these changes may not persist. CLINICALTRIAL UMIN000014146; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016466 (Archived by WebCite at http://www.webcitation.org/70o2rNk2V)

The mechanism underlying the vulnerability to developing schizophrenia (SCZ) during adolescence remains elusive. Hypofunction of N-methyl-d-aspartate receptors (NMDARs) has been implicated in the pathophysiology of SCZ. During development, the composition of synaptic NMDARs dramatically changes from NR2B-containing NMDARs to NR2A-containing NMDARs through the phosphorylation of NR2B S1480 or Y1472 by CDK5, CSNK2A1, and EphB2, which plays a pivotal role in the maturation of neural circuits. We hypothesized that the dysregulation of developmental change in NMDARs could be involved in the onset of SCZ. Using next-generation sequencing, we re-sequenced all the coding regions and splice sites of CDK5, CSNK2A1, and EphB2 in 474 patients with SCZ and 475 healthy controls. Variants on the database for human control subjects of Japanese origin were removed and all the nonsynonymous and nonsense variants were validated using Sanger sequencing. Four novel variants in CDK5 were observed in patients with SCZ but were not observed in controls. The total number of variants, however, was not significantly different between the SCZ and control groups (P=0.062). In silico analyses predicted P271T to be damaging. Further genetic research using a larger sample is required to examine whether CDK5 is involved in the pathophysiology of SCZ.

Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders. Although previous studies focused on the neurocognitive and socio-functional consequences of prefrontal and tempolo-limbic abnormalities in psychiatric disorders, those of subcortical structures remain largely unknown. Recently, MRI volume alterations in subcortical structures in patients with schizophrenia have been replicated in large-scale meta-analytic studies. Here we investigated the relationship between volumes of subcortical structures and neurocognitive and socio-functional indices in a large sample of patients with schizophrenia. First, we replicated the results of meta-analyses: the regional volumes of the bilateral hippocampus, amygdala, thalamus and nucleus accumbens were significantly smaller for patients (N = 163) than for healthy controls (HCs, N = 620). Second, in the patient group, the right nucleus accumbens volume was significantly correlated with the Digit Symbol Coding score, which is known as a distinctively characteristic index of cognitive deficits in schizophrenia. Furthermore, the right thalamic volume was significantly correlated with social function scores. In HCs, no significant correlation was found. The results from this large-scale investigation shed light upon the role of specific subcortical nuclei on cognitive and social functioning in schizophrenia.

Background Seeking help from others is an essential behavioural intention for humans to adapt to the social environment. Transgenerational and gender-related mechanisms of how this intention is shaped is an important but unresolved question in adolescent development. This study aimed to comprehensively examine the factors promoting or inhibiting intention to seek help for depression in 10-year-olds, including transgenerational factors, and to investigate the sex differences in the effect of these factors. Methods A cross-sectional study was conducted on a community of 4478 10-year-old children and their parents using self-report questionnaires and face-to-face interviews. The dependent variable was intention of seeking help for depression, which was assessed using a depression case vignette. Independent variables were demographic, psychological, and transgenerational/social factors including depressive symptoms, psychotic-like symptoms, tendency to help classmates, and parents’ help-seeking intention. Results Girls were more likely to seek help than boys. Multivariate logistic regression analysis showed that factors promoting help-seeking intention included the recognition of a need for help, emotional openness, tendency to help classmates, parents’ positive intention of seeking help for depression, and the number of people to consult. The inhibiting factors included depressive symptoms, psychotic-like symptoms, and gender norms regarding problem solving. Gender norms inhibited intention of seeking help for depression more strongly in boys than in girls. Conclusions Parents’ and children's help-seeking intention were correlated to each other. Actions should be considered against gender norms presuming that boys should solve their own problems. Further, these actions should target adults as much as adolescents.

Objective: The genetic and environmental influences on prefrontal function in childhood are underinvestigated due to the difficulty of measuring prefrontal function in young subjects, for which near‐infrared spectroscopy (NIRS) is a suitable functional neuroimaging technique that facilitates the easy and noninvasive measurement of blood oxygenation in the superficial cerebral cortices., Method: Using a two‐channel NIRS arrangement, we measured changes in bilateral prefrontal blood oxygenation during a category version of the verbal fluency task (VFT) in 27 monozygotic twin pairs and 12 same‐sex dizygotic twin pairs ages 5–17 years. We also assessed the participant's full‐scale intelligence quotient (FIQ) and retrieved parental socioeconomic status (SES). Classical structured equation modeling was used to estimate the heritability., Results: The heritability of VFT‐related brain activation was estimated to be 44% and 37% in the right and left prefrontal regions, respectively. We also identified a significant genetic contribution (74%) to FIQ, but did not to VFT task performance. Parental SES was not correlated with FIQ, task performance, or task‐related prefrontal activation., Conclusions: This finding provides further evidence that variance in prefrontal function has a genetic component since childhood and highlights brain function, as measured by NIRS, as a promising candidate for endophenotyping neurodevelopmental disorders.

Background The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia. Materials and Methods Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3 , and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument. Results and Discussion The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia.

Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n = 500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan platform. Case-control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P = 6.04 × 10(-7)), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD.

OBJECTIVE: This study reported a randomized controlled trial of the effectiveness of an Internet-based cognitive behavioral therapy (iCBT) program on work engagement and secondary work-related outcomes.METHODS: Participants who fulfilled the inclusion criteria were randomly allocated to an intervention or a control group (N = 381 for each). A 6-week, 6-lesson iCBT program using a Manga (Japanese comic) story was provided only to the intervention group. Work engagement was assessed at baseline and at 3- and 6-month follow-ups for both groups.RESULTS: The iCBT program showed a significant intervention effect on work engagement (P = 0.04) with small effect sizes (Cohen's d = 0.16 at 6-month follow-up).CONCLUSIONS: The study showed computerized cognitive behavior therapy delivered via the Internet to be effective (with a small effect size) in increasing work engagement in the general working population.TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000006210.

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.

INTRODUCTION: On 11 March 2011, a massive undersea earthquake, measuring 9.0 on the Richter scale, caused a tsunami that devastated the shoreline of east Japan. It is estimated that over 20,000 people lost their lives as a result. It is recommended that clinical effort after a tsunami disaster concentrate on a high-impact area rather than cover a large area. However, regional differences in post-traumatic stress symptoms among children after a tsunami disaster are not well clarified. METHODS: This study evaluated post-traumatic stress symptoms and reported the findings of early-phase screening of 2259 students from Higashi-Matsushima City, Japan, 6weeks after a tsunami hit the city. The sample was divided into two age groups: elementary school students (n=1102) and junior high school students (n=1157). Of these groups, 289 (26.2%) elementary school students and 123 (10.6%) junior high school students attended the four schools that were located in the area struck by the tsunami; the mortality rate of the area exceeded 4%. We referred to these students as the "high-impact group." The "lower-impact group" consisted of 813 (73.8%) elementary school students and 1034 (89.4%) junior high school students who attended the remaining ten schools. RESULTS: The severity of post-traumatic stress symptoms did not significantly differ between areas with relatively high and low impact. However, among the junior high school students, those attending the school in the highly impacted area showed higher post-traumatic symptoms scores than did the students of the less-impacted area. CONCLUSION: When planning a mass intervention after a disaster, especially in the early phase when the resources for intervention are not sufficient, it might be useful to consider the degree of age-dependent impact effect. Language: en

Epigenetic regulation may be involved in the pathophysiology of mental disorders, such as schizophrenia and bipolar disorder, and in the pharmacological action of drugs. Characterizing the epigenetic effects of drugs is an important step to optimal treatment. We performed comprehensive and gene-specific DNA methylation analyses of quetiapine using human neuroblastoma cells. Human neuroblastoma cells were cultured with quetiapine for 8 days, and DNA methylation analysis was performed using Infinium HumanMethylation27 BeadChip. A total of 1173 genes showed altered DNA methylation. Altered DNA methylation predominantly occurred as hypomethylation within the CpG island compared to DNA isolated from non-treated cells. Gene ontology analysis revealed that these genes were related to the cellular process of intracellular protein binding. There was no common effect of quetiapine with three mood stabilizers (lithium, valproate, and carbamazepine). However, common DNA methylation changes in eight genes, including ADRA1A, which encodes adrenoceptor alpha 1A, were found with quetiapine and lithium treatments. Finally, bisulfite-sequencing analysis revealed that quetiapine decreased the DNA methylation level of the promoter region of SLC6A4, where hypermethylation with bipolar disorder and hypomethylation with mood stabilizers have been reported.

Alterations in gamma-band auditory steady-state response (ASSR) are the most robust finding of abnormal neural oscillations in patients with first-episode (FES) and chronic schizophrenia. Gamma-band ASSRs may indicate GABAergic interneuron dysfunction. Nevertheless, it is unknown whether abnormal gamma-band ASSRs are present before the onset of psychosis. Subjects were 15 ultra-high-risk (UHR) individuals, 13 FES patients, and 21 healthy control (HC) subjects. We performed electroencephalogram recordings and measured ASSRs in each group as they were presented with click trains at 20, 30, and 40 Hz. We then conducted time-frequency analyses and calculated intertrial phase coherence and event-related spectral perturbation. The time course of gamma-band ASSRs showed significantly different features among groups. Compared with the HC group, the UHR group was characterized by intact early-latency (0-100 ms) and reduced late-latency (300-500 ms) ASSRs. In contrast, both early- and late-latency ASSRs were significantly reduced in the FES group. Gamma-band ASSRs were correlated with clinical symptoms and attentional functioning in FES (|rs| > 0.70). These results suggest differential alterations of gamma-band ASSRs between UHR and FES groups. The late-latency ASSR alteration may represent a biomarker for early detection of psychosis, while the early-latency ASSR abnormality may develop through the onset of psychosis.