Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Prevention of transgenerational transmission of disease susceptibility through perinatal intervention.

The observational findings of Barker's original epidemiological studies were generalized as the Barker hypothesis and extended as the Developmental Origins of Health and Disease (DOHaD) theory. Barker et al. proposed that low birthweight (LBW) was associated with the occurrence of various noncommunicable diseases (NCDs) later in life. In other words, LBW itself is associated with the development of NCDs. This led to the DOHaD theory which proposed that an organism may have a specific period of developmental plasticity that is highly sensitive to the factors in its environment, and that combinations of acquired constitution and environmental factors may adversely affect health and risk the formation of NCDs. Due to undernutrition during the fetal period, the fetus acquires an energy-saving constitution called a thrifty phenotype due to adaptations of the metabolic and endocrine systems. It has been suggested that stimuli experienced early in development can persist throughout life and induce permanent physiological changes that predispose to NCDs. It has since become clear that the adverse environmental effects during the prenatal period are also intergenerationally and transgenerationally inherited, affecting the next generation. It has been shown that nutritional interventions such as methyl-donner and epigenome editing can restore some of the impaired functions and reduce the risk of developing some diseases in the next generation. This review thus outlines the mechanisms underlying various disease risk formations and their genetic programs for the next generation, which are being elucidated through studies based on our fetal undernutrition rat models.

Perceptions of and subjective difficulties with social cognition in schizophrenia from an internet survey: Knowledge, clinical experiences, and awareness of association with social functioning.

AIM: Social cognition impacts social functioning in schizophrenia; however, little is known about how patients with schizophrenia themselves perceive social cognition. This study, using an internet survey, aimed to investigate their knowledge of social cognition, clinical experiences related to social cognition, awareness of social cognition's role in one's social life, and the relationships between subjective difficulties with social cognition and social functioning. METHODS: Data from 232 outpatients with schizophrenia (SZ) and 494 healthy controls (HC) were obtained through an internet survey and were weighted according to the demographics of the national population. A newly developed survey questionnaire on knowledge, experience, and awareness of social cognition was administered. Subjective difficulties were evaluated using the Self-Assessment of Social Cognition Impairments and the Observable Social Cognition Rating Scale. RESULTS: Less than a quarter of both groups were familiar with the term or concept of social cognition. Less than 5% of both groups had experienced being assessed or treated for social cognition. More than half of both groups were aware of the relationship between social cognition and social functioning. The SZ group had higher levels of subjective difficulties than the HC group across all social cognitive domains. The attributional bias domain of subjective difficulties was negatively associated with social functioning. CONCLUSION: Patients with schizophrenia had substantial subjective difficulties in social cognition, which they perceived as being related to social functioning. However, their knowledge of social cognition was limited, and the assessment and treatment might not be widespread in regular clinical practice.

Molecular Mechanisms Underlying Stress Response and Resilience.

A variety of stressors induce various physiological responses by modulating sympathetic, neuroendocrine, and behavioral systems [...].

Psychological impacts of the COVID-19 pandemic on one-month postpartum mothers in a metropolitan area of Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has recently become the most important issue in the world. Very few reports in Japan have examined the impact of the COVID-19 pandemic on peripartum mental health. We examined the status of postpartum mental health before and during COVID-19 pandemic from a consecutive database in a metropolitan area of Japan. METHODS: The subjects were women who had completed a maternity health check-up at a core regional hospital in Yokohama during the period from April 1, 2017, to December 31, 2020. We collected the subjects' scores for the Edinburgh Postnatal Depression Scale (EPDS) and the Mother-to-Infant Bonding Scale (MIBS) at 1 month postpartum. The subjects were divided into four groups (three Before COVID-19 groups and a During COVID-19 group). MANOVA and post-hoc tests were used to determine mental health changes in the postpartum period among the four groups. RESULTS: The Before and During COVID-19 groups contained 2844 and 1095 mothers, respectively. There were no significant difference in the total scores of the EPDS and MIBS among the four groups. However, the EPDS items related to anxiety factors were significantly higher and the EPDS items related to anhedonia and depression factors (excluding thoughts of self-harm) were significantly lower in the During COVID-19 group. CONCLUSION: The EPDS scores changed in connection with the COVID-19 pandemic. Anxiety, which represent hypervigilance, was significantly higher and anhedonia and depression were significantly lower in the During COVID-19 group. Our results may reflect COVID-19-related health concerns and a lack of social support caused by the COVID-19 pandemic.

Statistical Evaluation of Total Expiratory Breath Samples Collected throughout a Year: Reproducibility and Applicability toward Olfactory Sensor-Based Breath Diagnostics.

The endogenous volatile organic compounds (VOCs) in exhaled breath can be promising biomarkers for various diseases including cancers. An olfactory sensor has a possibility for extracting a specific feature from collective variations of the related VOCs with a certain health condition. For this approach, it is important to establish a feasible protocol for sampling exhaled breath in practical conditions to provide reproducible signal features. Here we report a robust protocol for the breath analysis, focusing on total expiratory breath measured by a Membrane-type Surface stress Sensor (MSS), which possesses practical characteristics for artificial olfactory systems. To assess its reproducibility, 83 exhaled breath samples were collected from one subject throughout more than a year. It has been confirmed that the reduction of humidity effects on the sensing signals either by controlling the humidity of purging room air or by normalizing the signal intensities leads to reasonable reproducibility verified by statistical analyses. We have also demonstrated the applicability of the protocol for detecting a target material by discriminating exhaled breaths collected from different subjects with pre- and post-alcohol ingestion on different occasions. This simple yet reproducible protocol based on the total expiratory breath measured by the MSS olfactory sensors will contribute to exploring the possibilities of clinical applications of breath diagnostics.

Prenatal and Postnatal Methyl-Modulator Intervention Corrects the Stress-Induced Glucocorticoid Response in Low-Birthweight Rats.

Low body weight at birth has been shown to be a risk factor for future metabolic disorders, as well as stress response abnormalities and depression. We showed that low-birthweight rats had prolonged high blood corticosterone levels after stress exposure, and that an increase in Gas5 lncRNA, a decoy receptor for glucocorticoid receptors (GRs), reduces glucocorticoid responsiveness. Thus, we concluded that dampened pituitary glucocorticoid responsiveness disturbed the glucocorticoid feedback loop in low-birthweight rats. However, it remains unclear whether such glucocorticoid responsiveness is suppressed solely in the pituitary or systemically. The expression of Gas5 lncRNA increased only in the pituitary, and the intact induction of expression of the GR co-chaperone factor Fkbp5 against dexamethasone was seen in the liver, muscle, and adipose tissue. Intervention with a methyl-modulator diet (folate, VB12, choline, betaine, and zinc) immediately before or one week after delivery reversed the expression level of Gas5 lncRNA in the pituitary of the offspring. Consequently, it partially normalized the blood corticosterone levels after restraint stress exposure. In conclusion, the mode of glucocorticoid response in low-birthweight rats is impaired solely in the pituitary, and intervention with methyl-modulators ameliorates the impairment, but with a narrow therapeutic time window.

Colloidal transport in bacteria suspensions: from bacteria collision to anomalous and enhanced diffusion.

Swimming microorganisms interact and alter the dynamics of Brownian particles and tend to modify their transport properties. In particular, dilute colloids coupled to a bath of swimming cells generically display enhanced diffusion on long time scales. This transport dynamics stems from a subtle interplay between the active and passive particles that still resists our understanding despite decades of intense research. Here, we tackle the root of the problem by providing a quantitative characterisation of the single scattering events between a colloid and a bacterium, a smooth running E. coli. Based on our experiments, we build a minimal model that quantitatively predicts the geometry of the scattering trajectories, and enhanced colloidal diffusion at long times. This quantitative confrontation between theory and experiments elucidates the microscopic origin of enhanced transport. Collisions are solely ruled by stochastic contact interactions and the ratio of the drag coefficients of the colloid and the bacteria. Such description accounts both for genuine anomalous diffusion at short times and enhanced diffusion at long times with no ballistic regime at any scale.

Demographic and clinical characteristics of foreign nationals accessing psychiatric services in Japan: a multicentre study in a metropolitan area.

BACKGROUND: International immigration to Japan, where homogeneous ethnicity is a population characteristic, has been growing. Although immigration is recognised as a risk factor for multiple mental-health related issues, there are few regional reports on foreign nationals accessing the psychiatric services in Japan. We aimed to reveal their current status and provide information to develop an optimal service system. METHODS: A multicentre retrospective document review research was conducted. The subjects were foreign nationals who resided in Japan and presented at the psychiatry departments in three core regional hospitals in the Keihin region, which faces Tokyo Bay and is well known to include the largest traditional industrial zone in Japan, over a period of 3 years. We investigated the patients' demographic and clinical information including country/region of origin, spoken language, use of a medical interpreter, pathway to hospitals and outcome. RESULTS: The percentage of foreign patients among all patients (1.4%) was quite low. Their age distribution (45.8 years on average) was dissociated from the age distribution of foreign nationals who resided in Japan. Regarding the country/region of origin, China (35.1%) was the most common country, followed by the Philippines, Korea and Brazil. Several subjects (22.9%) could not speak Japanese; therefore, interpretation was required by family members/friends (17.1%) or a professional interpreter (5.4%). Neurotic and stress-related disorders were the most common diagnosis (24.4%). The proportion of psychoactive substance use was higher than that for Japanese national data as immigrants are known to be at risk for it. CONCLUSIONS: The results suggest that foreign nationals who reside in Japan are less likely to contact appropriate services for mental illness, especially young people at relatively high risk of mental illness do not access services. Furthermore, lack of medical interpreters may impede the mental health conditions of foreign nationals. The development of a community-based integrated care system accessible to foreign nationals seems to be indispensable.

Community transition at younger ages contributes to good cognitive function outcomes in long-term hospitalized patients with schizophrenia spectrum disorder: A 15-year follow-up study with group-based trajectory modeling.

AIM: Cognitive dysfunction is a core symptom of schizophrenia spectrum disorder, but the reported long-term cognitive outcomes are heterogeneous. This study aimed to elucidate the long-term trajectories of patients with schizophrenia spectrum disorder who transitioned to community dwelling with integrated care, and to identify predictors of successful community reintegration. METHODS: After the closure of a psychiatric hospital, 78 patients with schizophrenia spectrum disorder (mean age: 54.6 years) were transferred to the community. We assessed patients' cognitive function over 15 years with the Mini-Mental State Examination (MMSE) and analyzed the scores every 3 years. Forty-four patients completed all assessments. RESULTS: The mean MMSE score at discharge was 25.8, which changed to 26.8 after 3 years and 25.3 after 6 years. After 12 and 15 years, it had decreased significantly to 23.3 and 23.0, respectively. Group-based trajectory modeling identified two groups of patients: a 'poor-outcome' group (63.4%), showing a decline in scores after maintaining post-discharge levels for several years, and a 'good-outcome' group (36.6%), maintaining post-discharge scores after showing improved scores. CONCLUSION: Considering the significant difference in age between the aforementioned groups (P = 0.040), we suggest that community transitions at younger ages contribute to better cognitive function and adaptation to community life. Even middle-aged and elderly patients with chronic schizophrenia spectrum disorder showed improved or maintained cognitive function at least 3 years after discharge, and the good-outcome group maintained cognitive function over 15 years. Improvements were dominated primarily by age at discharge, with cognitive function being maintained longer in patients in the good-outcome group.

A new action of peptide hormones for survival in a low-nutrient environment.

Malnutrition occurs when nutrient intake is too low for any reason and occurs regardless of gender or age. Therefore, besides loss of eating or digestive functionality due to illness, malnutrition can occur when a healthy individual undergoes an extreme diet and biases their nutrition, or when athletes exerts more energy than they can replenish through food. It has recently been reported that in Japan, the mortality rate of leaner individuals is equal to or higher than that of obese people. It is important to understand what homeostatic maintenance mechanism is behind this when the body is under hypotrophic conditions. Such mechanisms are generally endocranially controlled. We address this fundamental concern in this paper by focusing on peptide hormones. We introduce a mechanism for survival in a malnourished state via the regulation of food intake and temperature. Additionally, we will discuss the latest findings and future prospects for research on changes in the endocrine environment associated with malnutrition associated with exercise. We also review changes in next-generation endocrine environments when caused by malnutrition brought on by dieting.

Social anxiety and negative symptoms as the characteristics of patients with schizophrenia who show competence-performance discrepancy in social functioning.

AIM: Although competence and performance in relation to social functioning usually go hand in hand, it is not uncommon to observe a discrepancy between the two in patients with schizophrenia. The present study was aimed at examining the characteristics of patient groups showing such discrepancy. METHODS: A total of 205 outpatients with schizophrenia aged ≤40 years old were enrolled. The symptomatology and social functioning were widely assessed. The patients were divided into four groups by the cut-off scores for competence and performance in relation to social functioning calculated using a comprehensive dataset. RESULTS: The subjects were divided according to their level of competence and performance as follows: high competence and high performance (CP) group, 108 (52.7%) patients; high competence, but low performance (Cp) group, 40 (19.5%) patients; low competence, but high performance (cP) group, 13 (6.3%) patients; low competence and low performance (cp) group, 44 (21.5%) patients. One-way analysis of variance and post-hoc comparisons revealed significantly worse negative symptoms, general psychopathology scores, global functioning, and quality of life in the Cp group than in the CP group, and significantly better social anxiety symptoms, global functioning, and quality of life in the cP group than in the cp group. CONCLUSION: In patients who are capable, but do not perform well, negative symptoms may be involved in the discrepancy. Patients who are able to maintain themselves well despite low social competence appear to have milder social anxiety symptoms as compared to patients who are neither competent nor perform well.

Involvement of Noncoding RNAs in Stress-Related Neuropsychiatric Diseases Caused by DOHaD Theory : ncRNAs and DOHaD-Induced Neuropsychiatric Diseases.

According to the DOHaD theory, low birth weight is a risk factor for various noncommunicable chronic diseases that develop later in life. Noncoding RNAs (ncRNAs), including miRNAs, siRNAs, piRNAs, and lncRNAs, are functional RNA molecules that are transcribed from DNA but that are not translated into proteins. In general, miRNAs, siRNAs, and piRNAs function to regulate gene expression at the transcriptional and posttranscriptional levels. Studying ncRNAs has provided opportunities for new diagnosis and therapeutic knowledge in the endocrinological and metabolic fields as well as cancer biology. In this review, we focus on the roles of miRNAs and lncRNAs in the pathophysiology of stress-related neuropsychiatric diseases, which show abnormal blood hormone levels due to loss of feedback control and/or decreased sensitivity. Numerous recent studies have begun to unveil the importance of ncRNAs in regulation of stress-related hormone levels and functions. We summarize the involvement of abnormal ncRNA expression in the development of stress-related neuropsychiatric diseases based on the DOHaD theory.

Survey of recognition and treatment of at-risk mental state by Japanese psychiatrists.

AIM: The importance of early intervention in psychiatry is widely recognized among psychiatrists. However, it is unknown whether precise knowledge of at-risk mental state has been disseminated. With this survey, we aimed to reveal how Japanese psychiatrists diagnose patients with at-risk mental state and prescribe treatment strategies for them. METHODS: Using fictional case vignettes, we conducted a questionnaire survey of psychiatrists (n = 1399) who worked in Tokyo. We mailed study documents to all eligible participants in November 2015 with a requested return date in December. RESULTS: Two hundred and sixty (19.3%) psychiatrists responded to the survey. Their correct diagnosis rates for the patients in the at-risk mental state vignettes were low (14.6% for the vignette describing at-risk mental state with attenuated positive symptom syndrome; 13.1% for the vignette describing at-risk mental state with brief intermittent psychotic syndrome). Many psychiatrists selected pharmacotherapy and antipsychotics to treat patients in the at-risk mental state vignettes. The psychiatrists who correctly diagnosed patients in the at-risk mental state vignettes had significantly fewer years of clinical psychiatric experience than did those who diagnosed them as having a non-at-risk mental state (12.5 years vs 22.7 years for the vignette describing at-risk mental state with attenuated positive symptom syndrome, P < 0.01; 14.3 years vs 22.2 years for the vignette describing at-risk mental state with brief intermittent psychotic syndrome, P < 0.01). CONCLUSION: This study suggests that precise knowledge of at-risk mental state has not been disseminated among Japanese psychiatrists.

Finite-Size Scaling of a First-Order Dynamical Phase Transition: Adaptive Population Dynamics and an Effective Model.

We analyze large deviations of the time-averaged activity in the one-dimensional Fredrickson-Andersen model, both numerically and analytically. The model exhibits a dynamical phase transition, which appears as a singularity in the large deviation function. We analyze the finite-size scaling of this phase transition numerically, by generalizing an existing cloning algorithm to include a multicanonical feedback control: this significantly improves the computational efficiency. Motivated by these numerical results, we formulate an effective theory for the model in the vicinity of the phase transition, which accounts quantitatively for the observed behavior. We discuss potential applications of the numerical method and the effective theory in a range of more general contexts.

Stigma toward psychosis and its formulation process: prejudice and discrimination against early stages of schizophrenia.

BACKGROUND: Stigma toward psychosis can prevent social attendance and help-seeking behavior. Early detection and intervention has been shown to improve patient outcome in schizophrenia. The aim of this study was to reveal the characteristics and formulation process of stigma toward each clinical stage of schizophrenia, taking people's backgrounds into consideration. METHODS: The participants consisted of three groups: general public, patients with mental illness, and psychiatric professionals. We performed a survey examining stigmas toward people with psychotic-like-experiences (PLE), at-risk mental state for psychosis (ARMS), schizophrenia, or depression. Prejudice was measured using a 21-item questionnaire, and discrimination was measured using the Social Distance Scale. RESULTS: The participants consisted of 149 people from the general public, 97 patients, and 119 psychiatric professionals. Generally, a similar pattern was observed among the groups in which prejudice and discrimination against PLE was mildest, followed by that against ARMS and depression, and finally schizophrenia. When the stigma of the general public was compared with that of psychiatric professionals, the prejudice and discrimination against PLE of the general public were both lower than those of the psychiatric professionals. However, the prejudice of the general public was stronger than that of the professionals for ARMS. Furthermore, the discrimination of the general public was stronger than that of the professionals for schizophrenia. CONCLUSIONS: The stigmas of mental illness differed according to the clinical stage, although the pattern of severity was similar among the three groups. A formulation process is suggested in which stigma toward schizophrenia develops from an attitudinal property (prejudice) against ARMS and a behavioral property (discrimination) against schizophrenia.

Longitudinal study examining abnormal white matter integrity using a tract-specific analysis in individuals with a high risk for psychosis.

AIM: Although volume reductions in the grey matter have been previously observed in individuals with an at-risk mental state (ARMS) for psychosis, the features of white matter integrity and their correlation with psychiatric symptoms remain unclear. METHODS: Forty-six ARMS subjects were examined using magnetic resonance imaging (MRI) to acquire diffusion tensor imaging (DTI); the subjects were also evaluated using the Scale of Prodromal Symptoms at baseline and at 52 weeks. Sixteen healthy controls also underwent MRI scanning. The DTI results were longitudinally analyzed using a tract-specific analysis to measure the fractional anisotropy (FA) values of the entire corpus callosum (CC), as well as its genu, trunk, and splenium. RESULTS: During the 52-week study period, seven patients developed psychosis (ARMS-P) and 39 did not (ARMS-NP). In the entire CC and the genu, trunk, and splenium of the CC, the FA values of the ARMS subjects were each significantly smaller than the respective values of the healthy controls at baseline. In the genu and trunk, the baseline FA values in the ARMS-NP group were, paradoxically, smaller than those of the ARMS-P group at baseline. Regarding the association between the FA values and psychiatric symptoms, a reduction in the FA value in the genu was significantly correlated with a deterioration of negative symptoms among the ARMS subjects. CONCLUSION: Abnormal white matter integrity in the CC may predict the long-term outcome of patients with prodromal psychosis, since negative symptoms are associated with poor functioning.

Adrenalectomy facilitates ATAT1 expression and α-tubulin acetylation in ACTH-producing corticotrophs.

Microtubules play an important role in the intracellular transport of secretory granules in endocrine cells and in mitosis and the maintenance of cell morphology and are composed of heterodimers of α- and ß-tubulin. α-Tubulin N-acetyltransferase 1 (ATAT1), which acetylates the lysine residue at position 40 of α-tubulin, functions not only in stabilizing microtubule structures and forming the primary cilium assembly but also in vesicular trafficking in neurons. However, the localization of ATAT1 and the role of α-tubulin acetylation in endocrine cells in the pituitary are still poorly understood. Corticotrophs in the anterior lobe of the pituitary produce and secrete adrenocorticotropin (ACTH). Although removal of the adrenal gland, a target organ of ACTH, is reported to promote the synthesis and secretion of ACTH in corticotrophs and to induce structural alterations in their organelles, uncertainty remains as to whether the acetylation of α-tubulin is involved in such intracellular events of corticotrophs. We investigate the expression and localization of ATAT1 and the acetylation of α-tubulin in the pituitary of normal and adrenalectomized rats. We find that ATAT1 is localized to the Golgi apparatus of endocrine cells in the anterior lobe of normal pituitary and that the expression levels of ATAT1 and acetylation levels of α-tubulin increase following adrenalectomy. These results agree with the hypothesis that the acetylation of α-tubulin by ATAT1 regulates the intracellular transport of secretory granules in corticotrophs.