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BackgroundLoneliness is the distressing feeling that arises when a person's network of social relations is perceived as being inadequate in some way. Research has linked loneliness to a number of detrimental health outcomes. There is also some evidence that lonely individuals are more likely to engage in poorer health behaviors. However, as yet, there has been comparatively little attention paid to the relation between loneliness and dietary behavior. In particular, there has been little focus on the association between loneliness and fruit and vegetable intake.ObjectiveThe aim of this cross-sectional study was to examine the association between loneliness and low fruit and vegetable consumption in the Japanese general population.MethodsData were analyzed from 3,410 Japanese adults collected in an online survey in early 2023. Information was obtained on past-week fruit and vegetable consumption with a single-item measure, while loneliness was assessed with the Three-Item Loneliness Scale. Information was also collected on sociodemographic characteristics, physical health status, health-risk behaviors and depressive symptoms. Logistic regression was used to assess associations.ResultsOne in twenty (5.3%) adults reported low fruit and vegetable consumption. In a fully adjusted analysis loneliness was associated with higher odds for low fruit and vegetable consumption (OR: 1.14, 95%CI: 1.04–1.26). In sex- and age-stratified analyses loneliness was significantly associated with low fruit and vegetable consumption in both women and middle-aged adults, although confidence intervals overlapped for this association across all of the sex and age groups in the fully adjusted analyses.ConclusionsLoneliness is associated with low fruit and vegetable consumption among adults in Japan. As loneliness and inadequate fruit and vegetable intake have both been linked to poorer health outcomes, the results of this study underscore the potential importance and public health benefits of reducing loneliness in Japan.

Abstract The rate of medication persistence was examined in patients with schizophrenia or schizoaffective disorder during switching from previously administered antipsychotics to brexpiprazole, a new dopamine D2 receptor partial agonist. A multicenter, single‐arm, open‐label 24‐week interventional study was conducted, consisting of two 12‐week consecutive periods: an initial switch (by plateau cross‐titration) with the subsequent period, followed by a second maintenance period. Prior antipsychotics were olanzapine or risperidone/paliperidone. The primary and secondary outcome measures were medication persistence rates after the first 12 weeks and changes from baseline in the Specific Levels of Functioning Scale (SLOF), Subjective Well‐being under Neuroleptic drug treatment Short form (SWNS), and Positive and Negative Syndrome Scale (PANSS) scores, respectively. In total, 79 patients were administered brexpiprazole and the medication persistence rate at 12 weeks was 78.5%, which was significantly higher than the predefined threshold of 65%. Regarding the prior medication, the persistence rate at 12 weeks was 84.6% for olanzapine and 72.5% for risperidone/paliperidone. Significant improvements from baseline were observed in the SLOF, SWNS, and PANSS scores. There were no adverse events of concern. Thus, brexpiprazole appeared to be a suitable antipsychotic on switching from olanzapine, risperidone, or paliperidone.

Abstract Aim Interview quality is an important factor in the success of clinical trials for major depressive disorder (MDD). There is a substantial need to establish a reliable, remote clinical assessment interview system that can replace traditional in‐person interviews. Methods We conducted a multicenter, randomized, unblinded, prospective, cross‐sectional study to assess the reliability of remote interviews in patients with MDD (UMIN000041839). Eligible patients with MDD underwent remote and in‐person sessions of the Montgomery‐Åsberg Depression Rating Scale (MADRS) assessment performed by different raters within 28 days of providing consent. Patients were randomized to a group first assessed using in‐person interviews and secondarily using remote interviews (in‐person‐first group) or a group first assessed by remote interviews and secondarily using in‐person interviews (remote‐first group). Nineteen trained people (15 clinical psychologists, 3 nurses, and 1 clinical laboratory technologist) performed interviews. Results Of 59 patients (in‐person‐first group, n = 32; remote‐first group, n = 27) who completed both remote and in‐person interviews, 51% (n = 30) were women; the mean age was 41.6 years (range, 21–64 years). There was a strong association between remote and in‐person MADRS scores (r = 0.891, kappa = 0.901). An overall intraclass correlation coefficient (ICC) of 0.886 (95% confidence interval, 0.877–0.952) indicated good consistency between MADRS scores in remote and in‐person interviews. The ICC decreased as the severity of depression increased. Conclusion Our results suggest remote interviews are a feasible alternative option to in‐person interviews in assessing symptom severity in MDD patients and could promote clinical trials in Japan.

IntroductionMembrane phospholipid abnormalities are considered a pathophysiological background for schizophrenia. The aim of the study was to explore in detail the fatty acid (FA) composition in patients with antipsychotic-free schizophrenia and its association with clinical symptoms and cognitive function.Materials and methodsErythrocyte membrane FAs were measured in 29 antipsychotic-free patients with schizophrenia (male/female = 11/18; mean [standard deviation] age=26.7 [7.9] years) and age and sex-matched 32 healthy volunteers. Clinical symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), and the Schizophrenia Cognition Rating Scale (SCoRS).ResultsEicosapentaenoic acid levels were lower in the schizophrenia group than in the healthy control group. In contrast, arachidonic acid and nervonic acid levels were higher in the schizophrenia group than in the control group. Nervonic acid levels were significantly associated with depression scores as measured by the PANSS. No FA levels were correlated with BACS score; however, oleic acid levels were significantly related to cognitive dysfunction, as measured by the SCoRS.ConclusionThese findings suggest that depressive symptoms along with cognitive dysfunction in daily living in schizophrenia may be linked to the FA composition abnormalities. Further studies will be needed to examine potential longitudinal FA changes during the course of schizophrenia as well as disease specificity.

Abstract Poorer mental health is linked to a lower likelihood of voting in elections. However, little is known about this association in non-Western settings. This study examined the association between psychological distress and voting in nine countries of the former Soviet Union (FSU). Data were analysed from 18,000 respondents aged ≥ 18 in Armenia, Azerbaijan, Belarus, Georgia, Moldova, Kazakhstan, Kyrgyzstan, Russia and Ukraine collected during the Health in Times of Transition (HITT) survey in 2010/11. Information was collected on previous voting behaviour and future voting intentions. Psychological distress was assessed with a 12-item scale. In pooled multivariable logistic regression analyses psychological distress was significantly associated with ‘never voting’ (not having voted previously or intending to vote in future) and ‘past voting only’ (having voted previously but not intending to vote in future). In stratified analyses psychological distress was linked to never voting in women and working-age adults. The significant association between psychological distress and voting was observed only in hybrid political regimes. Psychological distress is associated with a reduced likelihood of voting in FSU countries especially among women, working-age adults and those in hybrid political regimes.

Abstract Background Financial debt has been linked to poorer mental health. However, most research has been undertaken in western countries. This study examined the association between financial debt, worry about debt, and mental health in Japan, where there has been little specific focus on debt and its effects on mental health. Methods Data were analyzed from 3717 respondents collected in an online survey in 2023. Information on financial debt and worry about debt was collected with single-item questions. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scale were used to respectively collect information on depression and anxiety symptoms, while a single-item measure was used to obtain information on a recent history of suicidal ideation. Logistic regression was used to assess associations. Results Both financial debt (17.7%) and worry about debt (14.8%) were prevalent in the study sample. In fully adjusted analyses, compared to those with no debt and worry about debt, individuals who were worried about debt but had no debt, or who had debts and were worried about debt had significantly higher odds for suicidal ideation and depressive symptoms. In contrast, having debt but not being worried about debt was not associated with any of the mental health outcomes. Conclusion The results of this study suggest that worrying about debt is strongly associated with poorer mental health among Japanese adults. Interventions to address debt and its associated worries may be important for improving public mental health in Japan.

While many countries across the world have had difficulty in providing continuous coronavirus disease (COVID-19) vaccine boosters, in Japan, the number of COVID-19 vaccinations has increased rapidly in the past two years to the point where the vaccination booster numbers are now at the highest level in the world (by March 2023). Against this backdrop, this study aimed to determine the characteristics of individuals who either refused to be vaccinated or who were vaccinated multiple (five) times during this period. We analyzed data from a sample of 3710 Japanese adults that were collected in a nationwide, cross-sectional Internet survey that was undertaken in March 2023. Several demographics (e.g., age, education level, marital status, job status), medical conditions, daily smoking, and mental health/psychological factors (i.e., perceived stress, anxiety symptoms, loneliness) were associated with not having been vaccinated. Although the most frequently vaccinated status was also associated with some demographics (e.g., age, employment status), medical conditions, and daily smoking, other predictors such as having a COVID-19 infection history were unique to this outcome. Moreover, age-stratified analyses showed that depression (OR: 2.05, 95%CI: 1.08–3.89) and anxiety (OR: 3.87, 95%CI: 1.80–8.31) symptoms were associated with higher odds of being unvaccinated while loneliness was associated with lower odds for the most frequently vaccinated status (OR: 0.72, 95%CI: 0.54–0.96) among older adults (aged ≥ 60 years). The findings of this study indicate that many of the same factors are associated with vaccine hesitancy and being vaccinated multiple times among adults in Japan but that among older individuals, worse mental/psychological health problems may be important for vaccine hesitancy/infrequent vaccine uptake in an age range where the majority of individuals (57.7%) had been vaccinated five times.

Background: In a previous meta-analysis, the use of serotonin1A(5-HT1A) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT1A partial agonists in improving other domains of neurocognitive function in schizophrenia patients. Methods: A literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis. Results: 5-HT1A partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = −0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = −0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = −0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = −0.10, 95 % CI = −0.53 to 0.33). Conclusions: The absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT1A agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.

Background: Exposure to natural disaster media coverage is associated with mental health problems, but its long-term impacts are still unclear. Also, no study has analysed the psychological impact of exposure to natural disaster media coverage among children who are generally sensitive to threatening events. Objective: We aimed to examine how television images of victims after the 2011 Great East Japan Earthquake were associated with mental health among children and their parents. Methods: In 2012, questionnaires for sociodemographic factors were distributed to 2053 families. Parents who provided written consent were contacted in 2013 and invited to provide information on mental health problems (outcome) and retrospectively provide information on television watching at the time of the earthquake (exposure). We used data from 159 parents who completed the survey as the final sample. We used a dichotomous variable to evaluate exposure to media coverage. Multivariable regression was used to examine the association between exposure to television images of victims and mental health, adjusting for potential confounders. Bias-corrected and accelerated bootstrap confidence intervals (CIs) were used. Results: Exposure to television images of victims was significantly associated with worse psychopathology among children (β, 1.51; 95% CI, 0.07–2.96) and greater psychological distress among their parents (β, 1.49; 95% CI, 0.28–2.70). Child psychopathology and parental psychological distress were significantly correlated (r = 0.36, p

BackgroundsPatients with schizophrenia suffer from cognitive impairment that worsens real-world functional outcomes. We previously reported that multi-session transcranial direct current stimulation (tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) improved daily living skills, while stimulation on the left superior temporal sulcus (STS) enhanced performance on a test of social cognition in these patients. To examine the region-dependent influence of tDCS on daily-living skills, neurocognition, and psychotic symptoms, this study compared effects of anodal stimulation targeting either of these two brain areas in patients with schizophrenia.MethodsData were collected from open-label, single-arm trials with anodal electrodes placed over the left DLPFC (N = 28) or STS (N = 15). Daily-living skills, neurocognition, and psychotic symptoms were measured with the UCSD performance-based skills assessment-brief (UPSA-B), Brief Assessment of Cognition in Schizophrenia (BACS), and Positive and Negative Syndrome Scale (PANSS), respectively. After baseline evaluation, tDCS (2 mA × 20 min) were delivered two times per day for 5 consecutive days. One month after the final stimulation, clinical assessments were repeated.ResultsPerformance on the UPSA-B was significantly improved in patients who received anodal tDCS at the left DLPFC (d = 0.70, p

IntroductionAbnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES).Materials and methodsThis study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS).ResultsEicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30).DiscussionThe findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

Abstract Background Recently, there has been a growing recognition that autistic traits exist along a continuum beyond diagnostic categories and that even subclinical symptoms may be associated with an increased risk for the psychosocial well-being and mental health of children. However, as yet, there has been little research on whether preschool children with autism spectrum disorder (ASD) symptoms, who do not meet the diagnostic criteria for ASD, are more likely to experience difficulties. To address this deficit this study examined whether young children with subthreshold autistic traits have an increased risk for emotional/behavioral difficulties. Methods Data were analyzed from 1057 Japanese preschool children aged 5-years old collected during the first wave of the Tama Children’s Survey (TCS) cohort study. Parent-reported autistic traits were assessed with the Social Responsiveness Scale (SRS), while they provided information on their child’s emotional/behavioral problems using the Strengths and Difficulties Questionnaire (SDQ). Logistic regression analysis was used to examine associations. Results Preschool children with mild-to-moderate autistic traits, corresponding to subclinical autism were significantly more likely to score above the clinical thresholds for emotional/behavioral problems compared to children with fewer autistic traits. Follow-up diagnostic assessments and analyses of 72 children from the cohort confirmed these findings and showed that these children with subthreshold autistic traits also had a significantly lower intelligence quotient (IQ) as measured by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Conclusions Although subthreshold autistic traits are difficult to define due to the sometimes vague border between typical and atypical development, there may be a large number of preschool children with subthreshold autistic traits, who may have an increased risk for a variety of different emotional/behavioral difficulties as well as lower cognitive functioning.

ObjectiveAlthough research has indicated that the prevalence of attention-deficit/hyperactivity disorder (ADHD) may be elevated in individuals with psychotic disorders, as yet, there has been comparatively little research on this association and its effects among adults at the subclinical level. To address this deficit, the current study examined the association between psychotic experiences (PE) and ADHD symptoms in Japanese individuals and whether the presence of ADHD symptoms increases the risk for negative health outcomes in people with PE.MethodData were analyzed from an online sample of 1,452 individuals (age 18–89; 51.5% female) collected in 2021. Information on PE was obtained with the PRIME Screen-Revised (PS-R), while the Adult ADHD Self-Report Scale (ASRS) Screener was used to measure ADHD symptoms. Information was also obtained on a number of health outcomes including anxiety and depressive symptoms and suicidal ideation. Logistic regression was used to assess associations.ResultsIn a fully adjusted analysis PE were associated with almost three times higher odds for ADHD symptoms (OR: 2.92, 95%CI: 1.19–7.17). In an analysis that was restricted to individuals with PE, ADHD symptoms were associated with significantly increased odds for depressive symptoms, lifetime suicidal ideation, perceived stress and severe sleep problems.ConclusionADHD symptoms are present in some individuals with PE and increase the odds for several detrimental health outcomes in this population. Identifying co-occurring PE and ADHD/ADHD symptoms may facilitate treatment options and help prevent negative health outcomes in individuals with these conditions.

Abstract Little is known about socioeconomic differences in epilepsy mortality. This study examined educational inequalities in epilepsy mortality in the general population in the Baltic countries and Finland in 2000–2015. Education-specific mortality estimates for individuals aged 30–74 in Estonia, Latvia and Lithuania were obtained from census-linked mortality datasets while data for Finland came from the register-based population and death data file of Statistics Finland. Trends and educational inequalities in epilepsy mortality were assessed using age-standardised mortality rates (ASMRs) per 100,000 person years and age-adjusted mortality rate ratios (RRs) calculated using Poisson regression. ASMRs were higher in men than women in all countries. ASMRs reduced in 2000–2015 among all men and women except for Finnish women. Among men, an inverse educational gradient in epilepsy mortality in 2000–2007 widened in 2008–2015 with ASMRs falling among high and mid educated men in all countries but increasing among low educated men in three countries. An inverse educational gradient in female mortality remained in all countries throughout 2000–2015. Although epilepsy mortality fell in the Baltic countries and Finland (men only) in 2000–2015, this masked a clear inverse educational gradient in mortality that became steeper across the period.

ObjectiveAttention–deficit/hyperactivity disorder (ADHD) symptoms have been linked to suicidal behavior. However, little is known about the mechanisms involved in this association. This study examined ADHD symptoms and suicidal ideation during the COVID-19 pandemic and the role of self–perceived stress in this association.MethodData were analyzed from an online sample of 1,452 Japanese individuals aged 18 to 89 obtained in February 2021. Information was collected on past–year suicidal ideation. ADHD symptoms were assessed with the Adult ADHD Self–Report Scale (ASRS) Screener while stress was measured with the Perceived Stress Scale (PSS−14). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ−9), while the Generalized Anxiety Disorder scale (GAD−7) was used to assess anxiety symptoms. Logistic regression was used to examine associations.ResultsFifty–one (3.5%) individuals had ADHD symptoms, while more than one in ten (11.7%) of the respondents reported past–year suicidal ideation. In an analysis adjusted for sociodemographic factors, ADHD symptoms were associated with eight times higher odds for past–year suicidal ideation. However, adjusting the analysis for mental health variables (anxiety and depressive symptoms) attenuated the association which became non–significant (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 0.92–4.18). In contrast, in an analysis adjusted for mental health, individuals with ADHD symptoms and stress had significantly higher odds for suicidal ideation (OR: 3.72, 95%CI: 1.43–9.67) whereas, ADHD symptoms without stress were not linked to suicidal ideation (OR: 1.25, 95%CI: 0.38–4.18).ConclusionsSelf–perceived stress is important in the association between ADHD symptoms and suicidal ideation among individuals in Japan during the COVID-19 pandemic. Detecting and managing stress and its effects in individuals with ADHD/ADHD symptoms should be a therapeutic focus for improving health–related outcomes in this population both during the COVID-19 pandemic and beyond.

BackgroundSocial cognitive impairments adversely affect social functioning (e.g., employment status) in patients with schizophrenia. Although pharmacological interventions have been suggested to provide some benefits on social cognition, little information is available on the comparative efficacy of pharmacotherapy. Thus, the aim of this planned systematic review and network meta-analysis is to perform a quantitative comparison of the effects of various psychotropic drugs, including supplements, on social cognition disturbances of schizophrenia.MethodsThe literature search will be carried out using the PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov, and International Clinical Trials Registry Platform databases from inception onward. Randomized controlled trials that examined the efficacy of drugs in social cognitive disturbances will be included, based on the most recent studies and the broader literature than previously searched. This protocol defines a priori the methods that will be used for study selection, data collection, quality assessment, and statistical syntheses.DiscussionThe findings this work are expected to help promote the development of better therapeutics of social cognitive impairments in schizophrenia and related psychiatric conditions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42021293224].

Accumulating evidence suggests that deficits in perceptual inference account for symptoms of schizophrenia. One manifestation of perceptual inference is the central bias, i.e., the tendency to put emphasis on prior experiences over actual events in perceiving incoming sensory stimuli. Using an interval reproduction task, this study aimed to determine whether patients with schizophrenia show a stronger central bias than participants without schizophrenia. In the interval reproduction task, participants were shown a cross on a screen. The cross was replaced with a Gaussian patch for a predetermined time interval, and participants were required to reproduce the interval duration by pressing and releasing the space key. We manipulated the uncertainty of prior information using different interval distributions. We found no difference in the influence of prior information on interval reproduction between patients and controls. However, patients with SZ showed a stronger central bias than healthy participants in the intermediate interval range (approximately 450 ms to 900 ms). It is possible that the patients in SZ have non-uniform deficits associated with interval range or uncertainty of prior information in perceptual inference. Further, the severity of avolition and alogia was correlated with the strength of central bias in SZ. This study provides some insights into the mechanisms underlying the association between schizophrenic symptoms and perceptual inference.

BackgroundPatients with schizophrenia show impairments of social cognition, which cause poor real-world functional outcomes. Transcranial direct current stimulation (tDCS) delivered to frontal brain areas has been shown to partially alleviate disturbances of social cognition. In this study, we aimed to determine whether multisession tDCS targeting the superior temporal sulcus (STS), a brain region closely related to social cognition, would improve social cognitive performance in patients with schizophrenia.MethodsThis was an open-label, single-arm trial to investigate the benefits and safety of multisession tDCS over the left STS. Fifteen patients received tDCS (2 mA × 20 min) two times per day for 5 consecutive days. Anodal and cathodal electrodes were placed over the left STS and right supraorbital regions, respectively. Assessments with the Social Cognition Screening Questionnaire (SCSQ), the Hinting Task (HT), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Positive and Negative Syndrome Scale (PANSS) were conducted at baseline and 1 month after the final stimulation.ResultsSignificant improvements were found on theory of mind, as measured using the SCSQ (d = 0.53) and the HT (d = 0.49). These changes on social cognition were not correlated with those of neurocognition, as measured using the BACS or psychotic symptoms, as measured using the PANSS. There were no adverse events of serious/moderate levels attributable to tDCS.ConclusionThese results suggest that administration of multisession tDCS with anode stimulation targeting the left STS provides a novel strategy to improve functional outcomes in patients with schizophrenia.Ethics StatementThe National Center of Neurology and Psychiatry Clinical Research Review Board (CRB3180006) approved this study.Trial RegistrationThis study was registered within the Japan Registry of Clinical Trials (jRCTs032180026).

BackgroundBoth impairment and sex differences in social cognition and neurocognition have been documented in schizophrenia. However, whether sex differences exist in the association between social cognition and neurocognition are not known. We aimed to investigate the contribution of areas of neurocognition to theory of mind (ToM) and hostility bias, representing social cognition, according to sex in early course schizophrenia.MethodsIn this cross-sectional study, we assessed neurocognition using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS) and assessed the ToM and hostility bias subdomains of social cognition using the Social Cognition Screening Questionnaire (SCSQ) in 131 participants (65 female, 66 male) diagnosed with schizophrenia within 5 years of onset. Sex differences were analyzed using t-tests. The associations of neurocognitive subdomains with ToM and hostility bias according to sex were analyzed using multiple regression analysis. Results were adjusted by age, estimated premorbid intelligence quotient, and symptomatology.ResultsNo sex differences were found in ToM (p = 0.071) or hostility bias (p = 0.057). Higher verbal fluency was significantly associated with higher ToM in females (p < 0.01), whereas higher executive function was significantly associated with higher ToM in males (p < 0.05). Higher verbal fluency was significantly associated with lower hostility bias in females (p < 0.05), whereas neurocognition and hostility bias were not significantly associated in males.ConclusionThe results suggest that neurocognition associated with social cognition differ according to sex. These differences should be considered for more effective treatment of social cognition.

The rapid expansion of online job interviews during the COVID-19 pandemic is expected to continue after the pandemic has subsided. These interviews are a significant barrier for individuals with autism spectrum disorders (ASD). There is little evidence-based training for online job interviews for individuals with ASD, and the development of new trainings is expected. In an effort to facilitate online job interview skill acquisition for individuals with ASD, we developed a group-based online job interview training program using a virtual robot (GOT). In GOT, the interviewer and interviewee are projected as virtual robots on the screen. Five participants were grouped and performed the role of interviewee, interviewer, and evaluator. The participants performed all roles in a random order. Each session consisted of a first job interview session, feedback session, and second job interview session. The participants experienced 25 sessions. Before and after GOT, the participants underwent a mock online job interview with a human professional interviewer (MOH) to evaluate the effect of GOT. In total, 15 individuals with ASD took part in the study. The GOT improved self-confidence, motivation, the understanding of others' perspectives, verbal competence, non-verbal competence, and interview performance scores. There was also a significant increase in the recognition of the importance of the point of view of interviewers and evaluators after the second MOH compared to after the first MOH. Using a VR robot and learning the importance of interview skills by experiencing other perspectives (i.e., viewpoint of interviewer and evaluator) may have sustained their motivation and enabled greater self-confidence. Given the promising results of this study and to draw definitive conclusions regarding the efficacy of virtual reality (VR) robots for mock online job interview training, further studies with larger, more diverse samples of individuals with ASD using a longitudinal design are warranted.

Antipsychotic medications based on the dopamine hypothesis possess limited effects for negative symptoms and cognitive impairments of schizophrenia. Growing body of evidence suggests that redox dysregulation contributes to the pathophysiology of the illness. We synthesized new chemicals using apocynin and tandospirone as leading compounds, and tested their antioxidant properties. The new compounds (A-1, A-2, A-3, and A-4), olanzapine (OLA), and clozapine (CLZ) were examined in terms of the ⋅OH radical decreasing activity and the effects on intracellular reactive oxygen species (ROS) formation induced by X-irradiation in human lymphoma U937 cells. The effects of these drugs, given around the period of puberty (postnatal days; PD 49 to 62), on glutathione (GSH) levels, as well as the number of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons were evaluated in the medial prefrontal cortex (mPFC) of rats transiently exposed to MK-801 in the neonatal period. A-2, A-3, A-4, OLA, and CLZ decreased intracellular ⋅OH and OCl−. The novel compounds reversed the decrease in GSH concentrations and reduction of PV-positive neurons in the mPFC in the model rats. CLZ only decreased GSH levels while OLA did not show a significant effect on either measure. These findings suggest that the new compounds derived from apocynin and tandospirone elicit antioxidant properties, and may provide a novel therapeutic approach for the treatment of schizophrenia and its spectrum disorders.

Abstract Aims Dopamine (DA) hyperactivity causes overestimation of time, whereas DA hypoactivity produces its underestimation. DA activity also provides neurochemical substrates pertinent to several psychiatric conditions, such as schizophrenia and Tourette's syndrome. The overestimation of time sometimes exists in patients with Tourette's syndrome, but no reports have addressed time perception in relation to antipsychotic medications which typically act as DA receptor antagonists. We herein report a case of Tourette's syndrome, in which time estimation was differentially affected by risperidone (a DA antagonist) and aripiprazole (a DA partial agonist). Case A 27‐year‐old man who suffered from verbal and motor tics was treated with risperidone. His tic symptoms disappeared; however, he began to experience a strange feeling that “time is going too fast.” For example, “people walk more quickly compared to a normal pace.” These complaints were thought to represent underestimation of time. Then, risperidone was switched to oral aripiprazole to optimize DA transmissions, which resulted in the amelioration of these subjective feelings. Conclusion Our observations indicate that the underestimation of time may occur in patients with Tourette's syndrome who receive antipsychotic drugs with high DA D2 receptor blocking potency. This may support the concept that the estimation of time is influenced by DA activity.

Backgrounds: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique for the treatment of several psychiatric disorders, e.g., mood disorders and schizophrenia. Therapeutic effects of tDCS are suggested to be produced by bi-directional changes in cortical activities, i.e., increased/decreased cortical excitability via anodal/cathodal stimulation. Although tDCS provides a promising approach for the treatment of psychiatric disorders, its neurobiological mechanisms remain to be explored.Objectives: To review recent findings from neurophysiological, chemical, and brain-network studies, and consider how tDCS ameliorates psychiatric conditions.Findings: Enhancement of excitatory synaptic transmissions through anodal tDCS stimulation is likely to facilitate glutamate transmission and suppress gamma-aminobutyric acid transmission in the cortex. On the other hand, it positively or negatively modulates the activities of dopamine, serotonin, and acetylcholine transmissions in the central nervous system. These neural events by tDCS may change the balance between excitatory and inhibitory inputs. Specifically, multi-session tDCS is thought to promote/regulate information processing efficiency in the cerebral cortical circuit, which induces long-term potentiation (LTP) by synthesizing various proteins.Conclusions: This review will help understand putative mechanisms underlying the clinical benefits of tDCS from the perspective of neurotransmitters, network dynamics, intracellular events, and related modalities of the brain function.

Background: Beneficial effects of transcranial direct current stimulation (tDCS) are relevant to cognition and functional capacity, in addition to psychiatric symptoms in patients with schizophrenia. However, whether tDCS would improve higher-order cognition, e.g., semantic memory organization, has remained unclear. Recently, text-mining analyses have been shown to reveal semantic memory. The purpose of the current study was to determine whether tDCS would improve semantic memory, as evaluated by text-mining analyses of category fluency data, in patients with schizophrenia.Methods: Twenty-eight patients entered the study. Cognitive assessment including the category fluency task was conducted at baseline (before tDCS treatment) and 1 month after t administration of tDCS (2 mA × 20 min, twice per day) for 5 days, according to our previous study. The category fluency data were also obtained from 335 healthy control subjects. The verbal outputs (i.e., animal names) from the category fluency task were submitted to singular valued decomposition (SVD) analysis. Semantic memory structures were estimated by calculating inter-item cosines (i.e., similarities) among animal names frequently produced in the category fluency task. Data were analyzed longitudinally and cross-sectionally to compare the semantic structure within the patient group (i.e., baseline vs. follow-up) and between groups (patients vs. healthy controls). In the former, semantic associations for frequent items were compared in the form of cosine profiles, while in the latter, the difference in the magnitude of the correlations for inter-item cosines between healthy controls and patients (baseline, follow-up) was examined.Results: Cosine profiles in the patient group became more cluster-based (i.e., pet, carnivores, and herbivores) at follow-up compared to those at baseline, yielding higher cosines within subcategories. The correlational coefficient of inter-item cosines between healthy controls and patients was significantly greater at follow-up compared to baseline; semantic associations in patients approached the normality status after multi-session tDCS.Conclusions: To our knowledge, this is the first study to demonstrate the facilitative effect of tDCS on semantic memory organization in patients with schizophrenia. Text-mining analysis was indicated to effectively evaluate semantic memory structures in patients with psychiatric disorders.

COVID-19 has affected many areas of daily life, including communication and learning. Social distancing is essential to prevent the spread of COVID-19. In these situations, teaching communication skills is essential for helping individuals with autism spectrum disorders (ASD) reach their full potential. To provide communication education while maintaining social distancing, we developed a communication training system using a tele-operated robot. In this system, we prepared a PC and a robot for each participant. The participants were grouped in pairs and communicated with each other through the tele-operated robot. The objective of this study was to test whether this system can maintain motivation for training in individuals with ASD and whether our system was useful for improving communication skills. Participants were randomly assigned to one of two groups: the taking a class by teachers alone (TCT) group or robot-mediated communication exercise (RMC) group. Participants in the TCT group took a class about communication skills from their teacher. Participants in the RMC group, in addition to taking a class by teacher, were grouped in pairs and communicated with each other through the tele-operated robot once a week over 4 weeks (for a total of five sessions). In total, twenty individuals with ASD participated in the study. One-way ANOVA revealed that there were significantly greater improvements in being good at describing their thoughts to others, which was self-rated (F = 6.583; p = 0.019), and good at listening to the thoughts or feelings of others, which was rated by themselves (F = 5.635; p = 0.029) and their teacher (F = 5.333; p = 0.033). As expected, the motivation for training using this system was maintained during a session. Overall, this study revealed that our system was useful for improving communication skills (e.g., listening to the thoughts or feelings of others). Teaching communication skills under pandemic conditions is important, and this study demonstrated the feasibility of communication training using tele-operated robots.

BACKGROUND:The prevalence of dementia has increased rapidly in Japan, while the proportion of the population accounted for by working-age individuals is facing a sharp decline. Optimizing the balance between work and caregiving for persons with dementia is a major public health issue. AIMS:Using a nationally representative sample, this study investigated the working status of caregivers (CGs) for elderly people (care recipients) with dementia (CRDs) and assessed the effects of sociodemographic factors on this status. METHODS:Data were obtained from the 2013 Comprehensive Survey of the Living Conditions for CRDs and CGs (the latter aged 65 years or less). Individual data of CRDs and CGs were linked, and 452 pairs were extracted. The Japanese version of the Kessler 6 (K6) with a cut-off point of 13 was used to assess general psychological distress among CGs. Multivariable logistic regression analysis with the forward selection method was used to identify the predictors of their working status. RESULTS:Overall, the mean age of CGs was 57.1 ± 6.8 years, with 57.5% (260/452) performing paid work. Male sex, higher educational attainment, and having their own house were associated with having paid work for CGs, while higher age, spending almost all day performing nursing care, and participation in helping with toilet activities and laundry were associated with not performing paid work. CONCLUSIONS:Several sociodemographic factors, including nursing care-related factors, are associated with the employment status of CGs. Further research should examine detailed information on CRDs' activities of daily living, behavioral and psychological symptoms, medical service use, and social support to strengthen the system of supportive services for both CRDs and their CGs.

Positive symptoms of schizophrenia may be related to distortions in time perception. To examine this issue, we conducted a meta-analysis to determine whether positive symptoms are associated with deficits in time processing performance. MEDLINE and Web of Science were searched from January 1980 through March 2017, and all related articles and their references were scrutinized to find relevant studies. Studies were selected if they included participants with a diagnosis of schizophrenia, and reported data from behavioral measures of interval timing (e.g. duration discrimination and temporal order judgement). The results indicated that positive symptoms of schizophrenia are related with overestimation of interval timing (i.e., acceleration of the “internal clock”), and suggest that time perception may be associated with psychosis. Keywords: Interval timing, Positive symptoms, Psychosis, Time perception, Internal clock

Cognitive function is impaired in patients with schizophrenia-spectrum disorders, even in their prodromal stages. Specifically, the assessment of cognitive abilities related to daily-living functioning, or functional capacity, is important to predict long-term outcome. In this study, we sought to determine the validity of the Schizophrenia Cognition Rating Scale (SCoRS) Japanese version, an interview-based measure of cognition relevant to functional capacity (i.e. co-primary measure). For this purpose, we examined the relationship of SCoRS scores with performance on the Brief Assessment of Cognition in Schizophrenia (BACS) Japanese version, a standard neuropsychological test battery, and the Social and Occupational Functioning Assessment Scale (SOFAS), an interview-based social function scale. Subjects for this study (n = 294) included 38 patients with first episode schizophrenia (FES), 135 with chronic schizophrenia (CS), 102 with at-risk mental state (ARMS) and 19 with other psychiatric disorders with psychosis. SCoRS scores showed a significant relationship with SOFAS scores for the entire subjects. Also, performance on the BACS was significantly correlated with SCoRS scores. These associations were also noted within each diagnosis (FES, CS, ARMS). These results indicate the utility of SCoRS as a measure of functional capacity that is associated both with cognitive function and real-world functional outcome in subjects with schizophrenia-spectrum disorders.

Abstract Introduction Patients with dentatorubral‐pallidoluysian atrophy (DRPLA) sometimes elicit psychosis. First‐generation antipsychotic drugs have been reported to be effective in treating psychotic symptoms associated with the disease. However, little information is available on the benefits of second‐generation antipsychotic drugs (SGAs). Case We report on a 47‐year‐old man with DRPLA whose psychotic symptoms were effectively treated with quetiapine, one of the SGAs. He suffered from delusions, auditory hallucinations, and disorganized speech. Initially, other antipsychotic drugs were tried, but were withdrawn because of adverse effects before switching to quetiapine. Conclusion Our observations add to the notion that some of the SGAs are useful for ameliorating psychosis in DRPLA.

Patients with schizophrenia exhibit impairments in their social activity, intelligence quotient (IQ), daily living skills, and social function. Social activity is a high-order outcome measure of their lives. Here we attempted to longitudinally evaluate the effects of IQ, daily living skills, social function, psychiatric symptoms, and medications on social activity in patients with schizophrenia. The purpose of the current study is to identify the specific factor that affects longitudinal changes in social activity. Sixty-five patients with schizophrenia were assessed at two time points [time 2 (T2, follow-up) − time 1 (T1, baseline) = 1.71 ± 0.79 years]. Social activity, IQ, daily living skills, and social function were assessed using the Social Activity Assessment (SAA; h/week), short form of the Wechsler Adult Intelligence Scale (WAIS)-III (WAIS-SF), University of California San Diego (UCSD) Performance-Based Skills Assessment (UPSA), and Social Functioning Scale (SFS), respectively. IQ, daily living skills, social function, and social activity were significantly improved between T1 and T2 (t = 2.0–4.4, p = 0.048–3.60 × 10−5). IQ, daily living skills, and social function positively correlated with social activity (lowest p = 1.27 × 10−5), and psychiatric symptoms negatively correlated with social activity over time (lowest p = 3.26 × 10−9). The longitudinal change in social activity was independently and positively correlated with a change in social function (beta = 0.35, p = 4.63 × 10−3), particularly interpersonal communication (beta = 0.35, p = 4.32 × 10−3). The longitudinal changes in other factors did not directly affect the change in social activity (p > 0.05). Based on these findings, social activity is more affected by social function than by other factors.

Backgrounds: Social cognition deficits are a core feature of schizophrenia and deteriorate functionality of patients. However, evidence is sparse for the treatment effect on social cognition impairments in the early stage of psychosis. Here, we provide a systematic review of the literature on social cognitive impairment in early psychosis in relation to its intervention.Methods: A literature search was conducted on English articles identified by Web of Science and PubMed databases, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement.Results: Five papers met the inclusion criteria. Results from two studies of cognitive training and one study of modafinil indicate positive results regarding social cognition outcomes in patients with early psychosis. On the other hand, two studies with oxytocin and modafinil did not suggest such effects.Conclusions: Further research is warranted to explore the benefit of early intervention into disturbances of social cognition in psychoses.

Decisional capacity to consent is an emerging ethical and legal concept, and is closely related to self-determination of patients facing important medical decisions or research participations. Recently, the MacArthur Competence Assessment Tool (MacCAT), a semi-structured interview consisting of four dimensions (Understanding, Appreciation, Reasoning, and Expression of a Choice), was developed to assess the decisional capacity. Decision-making capacity in a group of patients with schizophrenia, as measured by the MacCAT, has been shown to be impaired in comparison with healthy control people. However, this does not necessarily mean the presence of impaired decisional capacity in all cases. Considering the real-world practice of obtaining informed consent from patients with schizophrenia, it is important to evaluate the relationship between psychopathological features and decisional capacity of the illness. Negative symptoms of schizophrenia have been demonstrated to be related to the ability to understand information relevant to the decision, reason rationally, and appreciate a situation and its consequences. On the other hand, positive symptoms, such as delusions and hallucinations have been an inconsistent correlate of poor capacity. Furthermore, some studies indicate that impairment of cognitive function, a core symptom of schizophrenia, could be more largely associated with decisional capacity than positive and negative symptoms. Therefore, it is reasonable to assume cognitive enhancement would enlarge the capacity to consent and promote autonomy in medical treatment and research participation in patients with schizophrenia. Further studies are warranted to elucidate this and related issues.

Background: Autism spectrum disorder (ASD) is associated with persistent impairments in adaptive functioning across multiple domains of daily life. Thus, investigation of the biological background of both adaptive and maladaptive behaviors may shed light on developing effective interventions for improving social adaptation in ASD. In this study, we examined the relationship between adaptive/maladaptive behaviors and the acoustic startle response (ASR) and its modulation, which are promising neurophysiological markers for ASD translational research.Method: We investigated the ASR and its modulation in 11 children with ASD and 18 with typical development (TD), analyzing the relationship between startle measures and adaptive/maladaptive behaviors assessed with the Vineland Adaptive Behavior Scales (VABS) Second Edition.Results: Peak-ASR latency was negatively correlated with the VABS total score and socialization domain score of adaptive behaviors, while the ASR magnitude for relatively weak stimuli of 75–85 dB was positively correlated with VABS maladaptive behavior scores. Prepulse inhibition (PPI) at the prepulse intensity of 70–75 dB was also correlated with VABS maladaptive behavior. However, these relationships did not remain significant after adjustment for multiple comparisons.Conclusions: Our results indicate that the prolonged peak-ASR latency of ASD children might be associated with impairment in the developmental level of adaptive behavior, and that the greater ASR magnitude to relatively weak acoustic stimuli and smaller PPI of ASD children might increase the risk of maladaptive behavior. Future studies that have larger sample sizes will be important for further elucidating the neurophysiological factors that underpin adaptive as well as maladaptive behaviors in ASD.

Although impaired social functioning, particularly poor employment status, is a cardinal feature of patients with schizophrenia and leads to decreased quality of life (QOL), few studies have addressed the relationship between these two clinical issues. The aim of this study was to determine whether employment status predicts subjective QOL and to evaluate a model in which functional capacity mediates the relationship between general cognitive performance and employment status. Ninety-three patients with schizophrenia were administered a comprehensive battery of cognitive tests, the UCSD Performance-based Skills Assessment-Brief version (UPSA-B), the Social Functioning Scale (SFS), and the Subjective Quality of Life Scale (SQLS). First, we evaluated a model for predicting the employment/occupation subscale score of the SFS using path analysis, and the model fitted well (χ2 (4) = 3.6, p = 0.46; CFI = 1.0; RMSEA

An important objective for researchers and clinicians is to gain a better understanding of the factors that underlie autism spectrum disorders (ASDs). It is possible that investigating objective and quantitative behavioral phenotypes and their relationship to clinical characteristics, such as autistic traits and other emotional/behavioral problems, might facilitate this process. Given this, in the current study we examined the link between locomotor dynamics and clinical characteristics, including autistic traits and emotional/behavioral problems, in children with ASD (n = 14) and typically developing (TD) children (n = 13). A watch-type actigraph was used to continuously measure locomotor activity which was assessed in terms of mean activity levels and the skewness of activity. Parents assessed quantitative autistic traits using the Japanese version of the Social Responsiveness Scale (SRS) and emotional and behavioral problems using the Japanese version of the Strengths and Difficulties Questionnaire (SDQ). Results showed that among all children, all-day activity was more negatively skewed, suggesting sporadic large all-day “troughs” in activity and was significantly correlated with the SRS social awareness subscale score (ρ = −0.446, p = 0.038). In addition, the more negatively skewed daytime locomotor activity was associated with the SDQ Hyperactivity Inattention subscale score (ρ = −0.493, p = 0.020). The results of this study indicate that investigating locomotor dynamics may provide one way to increase understanding of the neurophysiological mechanisms underlying the clinical characteristics of ASD.

Backgrounds: There is a debate regarding the optimal timing of discontinuation of antipsychotic drugs in patients with first episode psychosis (FEP) or schizophrenia. We aimed to provide a review of the literature on which strategy (medication maintenance vs. dose reduction/discontinuation) is more likely to maximize outcomes, such as cognition and social function.Methods: Using PubMed, the Cochrane Library and systematic reviews, articles published between 2007 and 2018 were reviewed, which investigated the effect of dose reduction/discontinuation vs. maintenance treatment on measures of cognition and/or social function in FEP and schizophrenia.Results: Six studies were identified; 2 studies reported on cognition while 4 studies concern social function. All studies except one reported that improvement of functional outcomes in remitted patients with FEP or schizophrenia allocated to a dose reduction/discontinuation arm was equal to or better than that in patients for whom medication doses were maintained. One trial of social function with a 1-year follow-up period found a greater improvement in the medication maintenance group, while no group difference was observed with 3-year and 10-year follow-up periods. On the other hand, a 7-year follow-up study found a superiority for the dose reduction/discontinuation regimen in terms of social outcome. Two studies on cognition with a short follow-up period reported a greater improvement for the dose reduction/discontinuation group.Conclusions: Information on cognition and social function has been relatively sparse. These measures of functional outcome should be considered in deciding which strategy of antipsychotic treatments is beneficial in individual cases with FEP or schizophrenia.

Several domains of cognitive function, e.g., verbal memory, information processing, fluency, attention, and executive function are impaired in patients with schizophrenia. Cognitive impairments in schizophrenia have attracted interests as a treatment target, because they are considered to greatly affect functional outcome. Electrophysiological markers, including electroencephalogram (EEG), particularly, event-related potentials, have contributed to psychiatric research and clinical practice. In this review, we provide a summary of studies relating electrophysiological findings to cognitive performance in schizophrenia. Electrophysiological indices may provide an objective marker of cognitive processes, contributing to the development of effective interventions to improve cognitive and social outcomes. Further efforts to understand biological mechanisms of cognitive disturbances, and develop effective therapeutics are warranted.

The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia.

BackgroundDisorganization of semantic memory in patients with schizophrenia has been studied by referring to their category fluency performance. Recently, data-mining techniques such as singular value decomposition (SVD) analysis have been reported to be effective in elucidating the latent semantic memory structure in patients with schizophrenia. The aim of this study is to investigate semantic memory organization in patients with schizophrenia using a novel method based on data-mining approach.MethodCategory fluency data were collected from 181 patients with schizophrenia and 335 healthy controls at the Department of Psychiatry, Osaka University. The 20 most frequently reported animals were chosen for SVD analysis. In the two-dimensional (2D) solution, item vectors (i.e., animal names) were plotted in the 2D space of each group. In the six-dimensional (6D) solution, inter-item similarities (i.e., cosines) were calculated among items. Cosine charts were also created for the six most frequent items to show the similarities to other animal items.ResultsIn the 2D spatial representation, the six most frequent items were grouped in the same clusters (i.e., dog, cat as pet cluster, lion, tiger as wild/carnivorous cluster, and elephant, giraffe as wild/herbivorous cluster) for patients and healthy adults. As for 6D spatial cosines, the correlations (Pearson’s r) between 17 items commonly generated in the two groups were moderately high. However, cosine charts created for the three pairs from the six most frequent animals (dog–cat, lion–tiger, elephant–giraffe) showed that pair-wise similarities between other animals were less salient in patients with schizophrenia.DiscussionSemantic memory organization in patients with schizophrenia, revealed by SVD analysis, did not appear to be seriously impaired in the 2D space representation, maintaining a clustering structure similar to that in healthy controls for common animals. However, the coherence of those animals was less salient in 6D space, lacking pair-wise similarities to other members of the animal category. These results suggests subtle but structural differences between the two groups. A data-mining approach by means of SVD analysis seems to be effective in evaluating semantic memory in patients with schizophrenia, providing both a visual representation and an objective measure of the structural alterations.

BackgroundA recent review reported that the median proportion of patients recovering from schizophrenia was 13.5% and that this did not change over time. Various factors including the duration of untreated psychosis, cognitive impairment, negative symptoms, and morphological changes in the brain influence the functional outcome of schizophrenia. The authors herein reviewed morphological changes in the brain of schizophrenia patients, effects of early intervention, and a direction of developing novel therapeutics to achieve significant improvement of the functional outcome.MethodsA selective review of the literature including studies from our department was performed.ResultsLongitudinal structural neuroimaging studies on schizophrenia revealed that volume reductions in the peri-Sylvian regions (e.g., superior temporal gyrus and insula), which are related to positive psychotic symptoms, progress around the onset (critical stage) of schizophrenia, but become stable in the chronic stage. On the other hand, morphological changes in the fronto-thalamic regions and lateral ventricle, which are related to negative symptoms, neurocognitive dysfunction, and the functional outcome, progress during both the critical and chronic stages. These changes in the peri-Sylvian and fronto-thalamic regions may provide a pathophysiological basis for Crow’s two-syndrome classification. Accumulated evidence from early intervention trials suggests that the transition risk from an at-risk mental state (ARMS) to psychosis is approximately 30%. Differences in the cognitive performance, event-related potentials (e.g., mismatch negativity), and brain morphology have been reported between ARMS subjects who later developed psychosis and those who did not. Whether early intervention for ARMS significantly improves the long-term recovery rate of schizophrenia patients remains unknown. With respect to the development of novel therapeutics, animal models of schizophrenia based on the N-methyl-d-aspartate receptor hypofunction hypothesis successfully mimicked behavioral changes associated with cognitive impairments characteristic of the disease. Furthermore, these animal models elicited histological changes in the brain similar to those observed in schizophrenia patients, i.e., decreased numbers of parvalbumin-positive interneurons and dendritic spines of pyramidal neurons in the frontal cortex. Some antioxidant compounds were found to ameliorate these behavioral and histological abnormalities.ConclusionEarly intervention coupled with novel therapeutics may offer a promising approach for substantial improvement of the functional outcome of schizophrenia patients.

Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1) to identify which outcome factors predict occupational functioning, quantified as work hours, and 2) to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB), the UCSD Performance-based Skills Assessment-Brief (UPSA-B), and the Social Functioning Scale Individuals’ version modified for the MATRICS-PASS (Modified SFS for PASS), respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly) and a multiple logistic regression analyses (predicting dichotomized work status based on work hours). ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60–70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

Patients with schizophrenia elicit several clinical features, such as psychotic symptoms, cognitive impairment, and subtle decline of intelligence. The latter two features become evident around the onset of the illness, although they may exist even before the disease onset in a substantial proportion of cases. Here, we review the literature concerning intelligence decline (ID) during the progression of schizophrenia. ID can be estimated by comparing premorbid and current intellectual quotient (IQ) by means of the Adult Reading Test and Wechsler Adult Intelligence Scale (WAIS), respectively. For the purpose of brief assessment, we have recently developed the WAIS-Short Form, which consists of Similarities and Symbol Search and well reflects functional outcomes. According to the degree of ID, patients were classified into three distinct subgroups; deteriorated, preserved, and compromised groups. Patients who show deteriorated IQ (deteriorated group) elicit ID from a premorbid level (≥10-point difference between current and premorbid IQ), while patients who show preserved or compromised IQ do not show such decline (90 or below 90, respectively. We have recently shown the distribution of ID in a large cohort of schizophrenia patients. Consistent with previous studies, approximately 30% of schizophrenia patients had a decline of less than 10 points, i.e., normal intellectual performance. In contrast, approximately 70% of patients showed deterioration of IQ. These results indicate that there is a subgroup of schizophrenia patients who have mild or minimal intellectual deficits, following the onset of the disorder. Therefore, a careful assessment of ID is important in identifying appropriate interventions, including medications, cognitive remediation, and social/community services.

Recent research on neuromodulation techniques, such as transcranial direct current stimulation (tDCS), for the treatment of schizophrenia has mainly focused on psychotic symptoms. We aimed to determine whether repetitive tDCS is efficacious in improving determinants of outcome, such as cognitive function, daily living skills, and depressive mood in patients with schizophrenia. Twenty-eight patients underwent tDCS (2 mA × 20 min) two times per day for 5 consecutive days. The anodal electrode was placed over the left dorsolateral prefrontal cortex while the cathodal electrode was placed over the right supraorbital region. One month after the last stimulation, there was a significant improvement on cognitive function, measured by the brief assessment of cognition in schizophrenia (d = 0.49). Significant effects were also shown on daily living skills (functional capacity), measured by the UCSD performance-based skills assessment-brief (d = 0.70). Depressive symptoms, measured by the Calgary depression rating scale, as well as psychotic symptoms measured by on the positive and negative syndrome scale positive and general psychopathology subscales also responded to the treatment (d = 0.38, d = 0.48, and d = 0.50, respectively). This is the first study to suggest that tDCS with the anodal electrode on the left prefrontal cortex improves functional capacity and depressive symptoms in patients with schizophrenia. These results may add to the concept that tDCS provides a strategy to enhance functional outcomes in patients with schizophrenia.Trial Registrationhttps://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000018556, UMIN000015953.

BackgroundsSeveral domains of cognitive function, including learning memory and executive function, are impaired in mood disorders. Also, the relationship between disturbances of these two cognitive domains has been suggested. In line with the recent initiative to establish a standard measure of cognitive decline in bipolar disorder, the present study was conducted to (1) test the criterion-related validity and test–retest reliability of the California Verbal Learning Test (CVLT)-II Japanese version, and (2) determine if type of word learning tasks (i.e., with or without a category structure) affects severity of verbal memory deficits in patients with subsyndromal bipolar disorder.MethodsThirty-six patients with bipolar disorder with mild symptoms and 42 healthy volunteers participated in the study. We first compared effect sizes for memory deficits in patients among the CVLT-II, Brief Assessment of Cognition in Schizophrenia (BACS), and Hopkins Verbal Memory Tests-Revised (HVLT-R). We next evaluated the correlations between scores of the CVLT-II vs. those of the BACS and HVLT-R. Bipolar patients were re-assessed with the same (standard) or alternate forms of the CVLT-II and HVLT-R 1 month later.ResultsScores on the CVLT-II 1–5 Free Recall and Long-delay Free Recall, as well as the HVLT-R Immediate Recall, but not the BACS List Learning were significantly lower for patients compared to control subjects. The effect sizes for cognitive decline due to the illness were comparable when measured by the CVLT-II and HVLT-R, ranging from 0.5 to 0.6. CVLT-II scores were significantly correlated with those of the HVLT-R and BACS. Test–retest reliability of the CVLT-II was acceptable, and no significant practice effect was observed when the alternate form was used. There was no consistent relationship between mood symptoms and performance on the CVLT-II.ConclusionThese results suggest the CVLT-II Japanese version is able to discriminate between bipolar disorder patients and healthy controls with good sensitivity and validity. Data in this study also indicate that the degree of verbal memory deficits in bipolar disorder may be influenced by memory organizational strategy.

The UCSD Performance-based Skills Assessment Brief (the UPSA-B) has been widely used for evaluating functional capacity in patients with schizophrenia. The utility of the battery in a wide range of cultural contexts has been of concern among developers. The current study investigated the validity of the Japanese version of the UPSA-B as a measure of functional capacity and as a co-primary for neurocognion. Sixty-four Japanese patients with schizophrenia and 83 healthy adults entered the study. The Japanese version of the UPSA-B (UPSA-B Japanese version) and the MATRICS Cognitive Consensus Battery Japanese version (MCCB Japanese version) were administered. Normal controls performed significantly better than patients, with large effect sizes for the Total and the subscale scores of the UPSA-B. Receiver Operating Characteristic (ROC) curve analysis revealed that the optimal cut-off point for the UPSA-B Total score was estimated at around 80. The UPSA-B Total score was significantly correlated with the MCCB Composite score and several domain scores, indicating the relationship between this co-primary measure and overall cognitive functioning in Japanese patients with schizophrenia. The results obtained here suggest that the UPSA-B Japanese version is an effective tool for evaluating disturbances of daily-living skills linked to cognitive functioning in schizophrenia, providing an identifiable cut-off point and relationships to neurocognition. Further research is warranted to evaluate the psychometrical properties and response to treatment of the Japanese version of the UPSA-B.

The number of patients with schizophrenia has increased over the past decade. Previously, many studies have been performed to establish its diagnostic criteria, prophylactic methods, and effective therapies. In this study, we analyzed whether the ratios of DNA methylation in CpG islands of the Shati/Nat8l is decreased in model mice of schizophrenia-like phenotype using genomic DNA collected from brain regions and peripheral blood, since the mouse model of schizophrenia-like phenotype, mice treated repeatedly with methamphetamine showed increase of Shati/Nat8l mRNA expression in our previous experiment. The ratios of Shati/Nat8l CpG island methylation were significantly decreased in both the nucleus accumbens and the peripheral blood of model mice compared with those of control mice. We also investigated Shati/Nat8l methylation in the blood of patients with schizophrenia. We found that Shati/Nat8l CpG island methylation ratios were lower in the patients with schizophrenia than in the healthy controls, which is consistent with our findings in the mice model. To our knowledge, this is the first study to show similar alterations in methylation status of a particular genomic DNA site in both the brain and peripheral blood of mice. Furthermore, the same phenomenon was observed in corresponding human genomic sequences of the DNA extracted from the peripheral blood of patients with schizophrenia. Based on our findings, DNA methylation profiles of the CpG island of Shati/Nat8l might be a diagnostic biomarker of schizophrenia.

BACKGROUND: A shorter duration of untreated psychosis has been associated with better prognosis in schizophrenia. In this study, we measured the duration mismatch negativity (dMMN), an event-related potential, and cognitive performance in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these neurocognitive measures predict progression to overt schizophrenia in ARMS subjects. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen ARMS subjects, meeting the criteria of the Comprehensive Assessment of At-Risk Mental State, 31 schizophrenia patients (20 first-episode and 11 chronic) and healthy controls (N=20) participated in the study. dMMN was measured by an auditory odd-ball paradigm at baseline. Neuropsychological performance was evaluated by the Japanese version of the Brief assessment of cognitive function of schizophrenia (BACS-J). The first-episode schizophrenia group showed significantly smaller amplitudes at frontal electrodes than did control subjects whereas chronic patients elicited smaller amplitudes at frontal and central electrodes, consistent with previous reports. During the follow-up period, 4 out of the 17 ARMS subjects transitioned to schizophrenia (converters) while 13 did not (non-converters). Specifically, dMMN amplitudes of non-converters did not differ from those of healthy controls, while converters showed significantly smaller dMMN amplitudes at some electrodes compared to control subjects. Converters performed significantly worse on tests of working memory, verbal fluency, and attention/information processing than did non-converters. There was a significant positive correlation between dMMN amplitudes at the frontal electrodes and verbal fluency, as measured by the BACS, in the AMRS subjects as a whole. CONCLUSIONS/SIGNIFICANCE: ARMS subjects who later developed schizophrenia elicited smaller dMMN amplitudes to begin with, compared to non-converters. Notably, we have provided the first evidence for the ability of verbal fluency to predict dMMN amplitudes in ARMS subjects. These findings are expected to add to the efforts for early diagnosis and intervention of schizophrenia.

INTRODUCTION: Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia. METHODS: Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J). RESULTS: Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. CONCLUSIONS: This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.