Comparison of the 12-item and 36-item versions of the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 using longitudinal data from community mental health outreach service users.

AIM: This study aimed to compare the 12-item and 36-item versions of the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 using longitudinal data from community mental health outreach service users. METHODS: Using data from Tokorozawa City mental health outreach service users in Japan, total and domain WHODAS-12 and WHODAS-36 scores were compared. First, we examined score-change differences by domain at the start of outreach services (T1) and 1 year later (T2) for each version. Next, we compared differences between the two versions using Pearson's correlation, Wilcoxon signed-rank test, and Bland-Altman analysis. RESULTS: Among 20 participants, total scores and scores of some domains (i.e., cognition, getting along, life activities, and participation) were significantly lower at T2 than at T1 on both versions (p < 0.010). WHODAS-36 scores were significantly lower at T2 than at T1 for the self-care domain (p = 0.018). Except for self-care, strong correlations were found between scores from the two versions (p < 0.001). In the Wilcoxon signed-rank test and Bland-Altman analysis, we found significant differences between the scores of the two versions in the mobility, self-care, and participation domains. There were no significant differences in the distribution or systematic errors between the two versions in scores for the other domains or total score. CONCLUSION: We found strong positive correlations between WHODAS-12 and WHODAS-36 total scores with no statistical differences between them. For some domains, differences in distribution and systematic errors were found.

Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia.

The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (ß = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (ß = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.

Long-Term Trends and Sociodemographic Inequalities of Emotional/Behavioral Problems and Poor Help-Seeking in Adolescents During the COVID-19 Pandemic.

PURPOSE: During the first 3 years of the coronavirus disease (COVID-19) pandemic, we investigated the long-term trends of emotional/behavioral problems and poor help-seeking behavior in adolescents and examined the sociodemographic inequalities in these trends. METHODS: A multiwave cross-sectional survey was conducted in Japan from October-November 2020, June-July 2021, and June-July 2022 using an anonymous questionnaire. Trends of emotional/behavioral problems (e.g., emotional symptoms, hyperactivity/inattention, and total difficulties) and poor help-seeking were tested using a chi-squared test with Bonferroni correction. The effects of sociodemographic factors (grade, gender, country of origin, and number of parents) on emotional/behavioral problems and poor help-seeking were examined by two mixed-effect logistic regression models: (1) with fixed effects for years and sociodemographic factors and (2) stratified by years if the interaction terms between years and each sociodemographic factor were significant. RESULTS: The prevalence of total difficulties and emotional symptoms was the highest in 2021. The number of adolescents reporting hyperactivity/inattention and poor help-seeking increased between 2020 and 2021 and remained high in 2022. Inequalities in emotional/behavioral problems and poor help-seeking behavior were found with respect to all sociodemographic factors. DISCUSSION: Despite the persistent emotional/behavioral problems, the results suggested that the number of adolescents who were unable to seek help increased during the COVID-19 pandemic. Additionally, heterogeneities in the trends with respect to grade, gender, country of origin, and number of parents were detected. Prioritized supports targeting those with sociodemographic disadvantages may be needed to mitigate these inequalities in response to the pandemic.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Alterations of auditory-evoked gamma oscillations are more pronounced than alterations of spontaneous power of gamma oscillation in early stages of schizophrenia.

Several animal models of schizophrenia and patients with chronic schizophrenia have shown increased spontaneous power of gamma oscillations. However, the most robust alterations of gamma oscillations in patients with schizophrenia are reduced auditory-oscillatory responses. We hypothesized that patients with early-stage schizophrenia would have increased spontaneous power of gamma oscillations and reduced auditory-oscillatory responses. This study included 77 participants, including 27 ultra-high-risk (UHR) individuals, 19 patients with recent-onset schizophrenia (ROS), and 31 healthy controls (HCs). The auditory steady-state response (ASSR) and spontaneous power of gamma oscillations measured as induced power during the ASSR period were calculated using electroencephalography during 40-Hz auditory click-trains. The ASSRs were lower in the UHR and ROS groups than in the HC group, whereas the spontaneous power of gamma oscillations in the UHR and ROS groups did not significantly differ from power in the HC group. Both early-latency (0-100 ms) and late-latency (300-400 ms) ASSRs were significantly reduced and negatively correlated with the spontaneous power of gamma oscillations in the ROS group. In contrast, UHR individuals exhibited reduced late-latency ASSR and a correlation between the unchanged early-latency ASSR and the spontaneous power of gamma oscillations. ASSR was positively correlated with the hallucinatory behavior score in the ROS group. Correlation patterns between the ASSR and spontaneous power of gamma oscillations differed between the UHR and ROS groups, suggesting that the neural dynamics involved in non-stimulus-locked/task modulation change with disease progression and may be disrupted after psychosis onset.

Service intensity of community mental health outreach among people with untreated mental health problems in Japan: A retrospective cohort study.

Aim: This study aimed to clarify the association between treatment status (untreated or treated) at the start of community mental health outreach services and service intensity. Methods: This retrospective cohort study was conducted using the Tokorozawa City mental health outreach service users' data. Treatment status at the start of service (exposure variable) and the service intensity (outcome variables) were taken from clinical records. Poisson regression and linear regression analyses were conducted. The frequency of medical or social service use 12 months after service initiation was also calculated. This study was approved by the Research Ethics Committee at the National Center of Neurology and Psychiatry (No. A2020-081). Results: Of 89 people, 37 (42%) were untreated. Family members in the untreated group were more likely to be targets or recipients of services than in the treated group (b = 0.707, p < 0.001, Bonferroni-adjusted p < 0.001). Compared to the treated group, the untreated group received fewer services themselves (b = -0.290, p = 0.005), and also fewer services by telephone (b = -0.252, p = 0.012); by contrast, they received more services at the health center (b = 0.478, p = 0.031) and for family support (b = 0.720, p = 0.024), but these significant differences disappeared after Bonferroni adjustment. At least 11% of people in the untreated group were hospitalized and 35% were outpatients 12 months after service initiation. Conclusion: Family involvement may be a key service component for untreated people. The service intensity with and without treatment may vary by service location.

The association between clinical symptoms and later subjective quality of life in individuals with ultra-high risk for psychosis and recent-onset psychotic disorder: A longitudinal investigation.

AIM: Subjective quality of life is a clinically relevant outcome that is strongly associated with the severity of clinical symptoms in individuals with ultra-high risk for psychosis and patients with recent-onset psychotic disorder. Our objective was to examine whether longitudinal changes in clinical symptoms are associated with quality of life in ultra-high risk individuals and patients with recent-onset psychotic disorder. METHODS: Individuals with ultra-high risk and patients with recent-onset psychosis disorder were recruited in the same clinical settings at baseline and were followed up with more than 6 months and less than 5 years later. We assessed five factors of clinical symptoms using the positive and negative syndrome scale, and quality of life using the World Health Organization quality of life questionnaire-short form. We used multiple regression to examine the relationships between clinical symptoms and quality of life while controlling for diagnosis, follow-up period, age, and sex. RESULTS: Data were collected from 22 individuals with ultra-high risk and 27 patients with recent-onset psychosis disorder. The multiple regression analysis results indicated that the more severe anxiety/depression was at baseline, the poorer the quality of life at follow-up. Further, improvement of anxiety/depression and disorganized thoughts were associated with improvement in quality of life. The difference in diagnosis did not affect the association between clinical symptoms and quality of life. CONCLUSION: These findings suggest that the improvement of anxiety/depression and disorganized thoughts is important in the early stages of psychosis before it becomes severe, affecting the quality of life.

Implementation of online classes during national school closure due to COVID-19 and mental health symptoms of adolescents: A cross-sectional survey of 5000 students.

Aim: Online classes were implemented in numerous schools during the school closure due to COVID-19. The present study examined the relationship between online classes during national school closure and mental health symptoms after the reopening of schools. Methods: We conducted a cross-sectional survey from October 1 to November 7, 2020 using an anonymous self-reported questionnaire to evaluate 21 junior and senior high schools in the Saitama prefecture of Japan. Out of the 5538 students who were recruited, 5000 agreed to participate. The relationship between the implementation of online classes and mental health symptoms (emotional symptoms, psychotic experience [PE], and smartphone addiction) was evaluated using mixed-effect logistic regression models, while controlling for individual and class-level covariates (e.g., gender, grades). Results: Implementation of online classes was reported by 78.2% of classroom teachers, and it was associated with lower rates of emotional symptoms (OR = 0.79, 95% CI = 0.63-0.99, p = 0.040) and smartphone addiction (OR = 0.79, 95% CI = 0.65-0.96, p = 0.020), but not related to PE (OR = 0.91, 95% CI = 0.61-1.36, p = 0.637). Conclusions: Implementing online classes during the national school closure might have had a potential protective effect for adolescents' mental health symptoms (especially emotional symptoms and smartphone addiction) after the reopening of schools during the ongoing COVID-19 pandemic.

Effects of the Attention Training Technique on Brain Activity in Healthy University Students Assessed by EEG Source Imaging.

This study aimed to investigate the neurocognitive effects of the Attention Training Technique (ATT) on brain activity in healthy participants. The participants included 20 university students who were asked to practice ATT as a homework assignment for 20 days. The intracerebral source localization of their electroencephalogram during rest and the ATT task, which comprised selective attention, attention switching, and divided attention conditions, was evaluated by standardized low-resolution brain electromagnetic tomography. Brain activity during rest was subtracted from that during the ATT task, and that was compared before and after the homework assignment. The results for the divided attention condition indicated significantly decreased alpha 1 frequency band power in the left orbital frontal cortex (OFC) and alpha 2 power in the right inferior temporal cortex. Further, decreased alpha 1 power in the left OFC correlated with reduced subjective difficulty during the divided attention condition. One possibility is that the brain activity changed as the effect of ATT practice, although this study cannot confirm causality. Further studies are required which include a control group that would complete similar training without the ATT task.

Young carers in Japan: Reliability and validity testing of the BBC/University of Nottingham young carers survey questionnaire and prevalence estimation in 5000 adolescents.

Aim: Young carers (YCs) refer to children under the age of 18 who assume responsibilities that would normally be assumed by adults, such as caring for family members in need of care. In recent years, the concept of YCs has been expanding in Japan, and the government has been rapidly implementing strategies to support them. There is a need for a survey scale for YCs that uses standardized methods that can be compared internationally. Method: The BBC/University of Nottingham Survey for estimating the prevalence of YCs and caring activities of United Kingdom adolescents was translated into Japanese, and its reliability and validity were tested with 313 adolescents. Moreover, the prevalence of YCs was estimated in a school-based survey among 5000 adolescents. Results: The Young Carers Scale Japanese version (YCS-J) was acceptably reliable and valid. The original six-factor model for caring activity in the Multidimensional Assessment of Caring Activities Checklist for Young Carers (MACA-YC18) was supported by confirmatory factor analysis. The prevalence of YCs among 5000 adolescents in the Tokyo metropolitan area was estimated to be 7.4%, comparable to that reported in Western countries and in recent surveys in Japan using nonstandardized methods. YCs exhibited significantly higher scores for prosocial behavior and emotional symptoms than non-YCs. Conclusions: The YCS-J, as an internationally comparable instrument, will be useful for understanding the actual situation of YCs in Japan, and to disseminate and implement support through cooperation among education, welfare, and healthcare sectors.

Criticality in the Healthy Brain.

The excellence of the brain is its robustness under various types of noise and its flexibility under various environments. However, how the brain works is still a mystery. The critical brain hypothesis proposes a possible mechanism and states that criticality plays an important role in the healthy brain. Herein, using an electroencephalography dataset obtained from patients with psychotic disorders (PDs), ultra-high risk (UHR) individuals and healthy controls (HCs), and its dynamical network analysis, we show that the brain of HCs remains around a critical state, whereas that of patients with PD falls into more stable states. Meanwhile, the brain of UHR individuals is similar to that of PD in terms of entropy but is analogous to that of HCs in causality patterns. These results not only provide evidence for the criticality of the normal brain but also highlight the practicability of using an analytic biophysical tool to study the dynamical properties of mental diseases.

Translatability of Scalp EEG Recordings of Duration-Deviant Mismatch Negativity Between Macaques and Humans: A Pilot Study.

Mismatch negativity (MMN) is a negative deflection of the auditory event-related potential (ERP) elicited by an abrupt change in a sound presented repeatedly. In patients with schizophrenia, MMN is consistently reduced, which makes it a promising biomarker. A non-human primate (NHP) model of MMN based on scalp electroencephalogram (EEG) recordings can provide a useful translational tool, given the high structural homology of the prefrontal and auditory cortices between NHPs, such as macaques, and humans. However, in previous MMN studies, the NHP models used did not allow for comparison with humans because of differences in task settings. Moreover, duration-deviant MMN (dMMN), whose reduction is larger than that in the frequency-deviant MMN (fMMN) in patients with schizophrenia, has never been demonstrated in NHP models. In this study, we determined whether dMMN can be observed in macaque scalp EEG recordings. EEGs were recorded from frontal electrodes (Fz) in two Japanese macaques. Consistent with clinical settings, auditory stimuli consisted of two pure tones, a standard and a deviant tone, in an oddball paradigm. The deviant and standard tones differed in duration (50 and 100 ms for the standard and deviant tones, respectively). A robust dMMN with a latency of around 200 ms, comparable to that in humans, was observed in both monkeys. A comparison with fMMN showed that the dMMN latency was the longer of the two. By bridging the gap between basic and clinical research, our results will contribute to the development of innovative therapeutic strategies for schizophrenia.

Mismatch Negativity Predicts Remission and Neurocognitive Function in Individuals at Ultra-High Risk for Psychosis.

BACKGROUND: In the early intervention in psychosis, ultra-high risk (UHR) criteria have been used to identify individuals who are prone to develop psychosis. Although the transition rate to psychosis in individuals at UHR is 10% to 30% within several years, some individuals at UHR present with poor prognoses even without transition occurring. Therefore, it is important to identify biomarkers for predicting the prognosis of individuals at UHR, regardless of transition. We investigated whether mismatch negativity (MMN) in response to both duration deviant stimuli (dMMN) and frequency deviant stimuli (fMMN) could predict prognosis, including remission and neurocognitive function in individuals at UHR. MATERIALS AND METHODS: Individuals at UHR (n = 24) and healthy controls (HC; n = 18) participated in this study. In an auditory oddball paradigm, both dMMN and fMMN were measured at baseline. Remission and neurocognitive function after > 180 days were examined in the UHR group. Remission from UHR was defined as functional and symptomatic improvement using the Global Assessment of Functioning (GAF) score and Scale of Prodromal Symptoms (SOPS) positive subscales. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia (BACS). We examined differences in MMN amplitude at baseline between those who achieved remission (remitters) and those who did not (non-remitters). Multiple regression analyses were performed to identify predictors for functioning, positive symptoms, and neurocognitive function. RESULTS: Compared with the HC group, the UHR group had a significantly attenuated dMMN amplitude (p = 0.003). In the UHR group, GAF scores significantly improved during the follow-up period (mean value 47.1 to 55.5, p = 0.004). The dMMN amplitude at baseline was significantly larger in the remitter (n = 6) than in the non-remitter group (n = 18) (p = 0.039). The total SOPS positive subscale scores and fMMN amplitude at baseline could predict BACS attention subscore at the follow-up point (SOPS positive subscales, p = 0.030; fMMN, p = 0.041). CONCLUSION: Our findings indicate that dMMN and fMMN predicted remission and neurocognitive function, respectively, in individuals at UHR, which suggests that there are both promising biomarker candidates for predicting prognosis in individuals at UHR.

A Predictive Coding Perspective on Mismatch Negativity Impairment in Schizophrenia.

Mismatch negativity (MMN) is a widely used biological marker for schizophrenia research. Previous studies reported that MMN amplitude was reduced in schizophrenia and that reduced MMN amplitude was associated with cognitive impairments and poor functional outcome in schizophrenia. However, the neurobiological mechanisms underlying the reduced MMN amplitude remain unclear. Recent studies suggest that reduced MMN amplitude may reflect altered predictive coding in schizophrenia. In this paper, we reviewed MMN studies that used new paradigms and computational modeling to investigate altered predictive coding in schizophrenia. Studies using the roving oddball paradigm and modified oddball paradigm revealed that the effects of conditional probability were impaired in schizophrenia. Studies using omission paradigms and many-standards paradigms revealed that prediction error, but not adaptation, was impaired in schizophrenia. A study using a local-global paradigm revealed that hierarchical structures were impaired at both local and global levels in schizophrenia. Furthermore, studies using dynamic causal modeling revealed that neural networks with hierarchical structures were impaired in schizophrenia. These findings indicate that altered predictive coding underlies the reduced MMN amplitude in schizophrenia. However, there are several unsolved questions about optimal procedures, association among paradigms, and heterogeneity of schizophrenia. Future studies using several paradigms and computational modeling may solve these questions, and may lead to clarifying the pathophysiology of schizophrenia and to the development of individualized treatments for schizophrenia.

Reduced Auditory Mismatch Negativity Reflects Impaired Deviance Detection in Schizophrenia.

The auditory mismatch negativity (MMN) is a translatable electroencephalographic biomarker automatically evoked in response to unattended sounds that is robustly associated with cognitive and psychosocial disability in patients with schizophrenia. Although recent animal studies have tried to clarify the neural substrates of the MMN, the nature of schizophrenia-related deficits is unknown. In this study, we applied a novel paradigm developed from translational animal model studies to carefully deconstruct the constituent neurophysiological processes underlying MMN generation. Patients with schizophrenia (N = 25) and healthy comparison subjects (HCS; N = 27) underwent MMN testing using both a conventional auditory oddball paradigm and a "many-standards paradigm" that was specifically developed to deconstruct the subcomponent adaptation and deviance detection processes that are presumed to underlie the MMN. Using a conventional oddball paradigm, patients with schizophrenia exhibited large effect size deficits of both duration and frequency MMN, consistent with many previous studies. Furthermore, patients with schizophrenia showed selective impairments in deviance detection but no impairment in adaptation to repeated tones. These findings support the use of the many-standards paradigm for deconstructing the constituent processes underlying the MMN, with implications for the use of these translational measures to accelerate the development of new treatments that target perceptual and cognitive impairments in schizophrenia and related disorders.

Resting-state EEG beta band power predicts quality of life outcomes in patients with depressive disorders: A longitudinal investigation.

BACKGROUND: Quality of life is severely impaired in patients with depressive disorders. Previous studies have focused on biomarkers predicting depressive symptomatology; however, studies investigating biomarkers predicting quality of life outcomes are limited. Improving quality of life is important because it is related not only to mental health but also to physical health. We need to develop a biomarker related to quality of life as a therapeutic target for patients with depressive disorders. Resting-state electroencephalography (EEG) is easy to record in clinical settings. The index of bandwidth spectral power predicts treatment response in depressive disorders and thus may be a candidate biomarker. However, no longitudinal studies have investigated whether EEG-recorded power could predict quality of life outcomes in patients with depressive disorders. METHODS: The resting-state EEG-recorded bandwidth spectral power at baseline and the World Health Organization Quality of Life (QOL)-26 scores at 3-year follow-up were measured in 44 patients with depressive disorders. RESULTS: The high beta band power (20-30 Hz) at baseline significantly predicted QOL at the 3-year follow-up after considering depressive symptoms and medication effects in a longitudinal investigation in patients with depressive disorders (ß = 0.38, p = 0.01). LIMITATIONS: We did not have healthy subjects as a comparison group in this study. CONCLUSIONS: Our findings suggest that resting-state beta activity has the potential to be a useful biomarker for predicting future quality of life outcomes in patients with depressive disorders.

Gamma-Band Auditory Steady-State Response as a Neurophysiological Marker for Excitation and Inhibition Balance: A Review for Understanding Schizophrenia and Other Neuropsychiatric Disorders.

Altered gamma oscillations have attracted considerable attention as an index of the excitation/inhibition (E/I) imbalance in schizophrenia and other neuropsychiatric disorders. The auditory steady-state response (ASSR) has been the most robust probe of abnormal gamma oscillatory dynamics in schizophrenia. Here, we review recent ASSR studies in patients with schizophrenia and other neuropsychiatric disorders. Preclinical ASSR research, which has contributed to the elucidation of the underlying pathophysiology of these diseases, is also discussed. The developmental trajectory of the ASSR has been explored and may show signs of the maturation and disruption of E/I balance in adolescence. Animal model studies have shown that synaptic interactions between parvalbumin-positive GABAergic interneurons and pyramidal neurons contribute to the regulation of E/I balance, which is related to the generation of gamma oscillation. Therefore, ASSR alteration may be a significant electrophysiological finding related to the E/I imbalance in neuropsychiatric disorders, which is a cross-disease feature and may reflect clinical staging. Future studies regarding ASSR generation, especially in nonhuman primate models, will advance our understanding of the brain circuit and the molecular mechanisms underlying neuropsychiatric disorders.

White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals.

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.

Mismatch negativity (MMN) as a tool for translational investigations into early psychosis: A review.

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.