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Purpose: Understanding affiliate stigma and its impact on family of people living with schizophrenia (PLS) in China is important for culturally informed intervention. This study aims to describe the pattern of affiliate stigma of family members of PLS in China and investigated the association between affiliate stigma and family burden., Methods: PLS and their family members dwelling in community were randomly recruited from four cities across China and completed measures of affiliate stigma and family burden. Linear regression analyses were used to determine the association between affiliate stigma and family burden., Results: A total of 493 dyads of family member and PLS were include in this study. The mean affiliate stigma in family members was 2.21 (SD = 0.61). The vast majority of family members reported the feeling of inferiority, helpless and sad because of their family members' schizophrenia, but few family members refusing to communicate or contact with the PLS. The mean score of overall family burden was 22.25 (SD = 14.90), with 98 % of participants reported moderate or severe burden. A higher level of affiliate stigma was associated with more family burden (b = 7.837, 95CI: 5.240 to 8.747). Affiliate stigma was significantly associated with family daily activities, entertainment activities, family relationship, physical health and mental health of family members, but not family economic burden., Conclusion: A higher level of affiliate stigma was associated with more family burden among family with PLS. Anti-stigma intervention of mental illness should be consider not only PLS but also their family members., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Hypothesis: This survey explores Swiss mental health professionals', users', and relatives' opinions on re-naming schizophrenia exploiting Switzerland's specific multilingualism to examine possible effects of linguistic and microcultural differences on the issue., Study Design: Opinions on 'schizophrenia' were collected using a self-rated online questionnaire incl. Freetext answers available in the three main Swiss languages, German, French and Italian. It was distributed to the main professional and self-help organizations in Switzerland between June and October 2021., Study Results: Overall, 449 persons completed the questionnaire, 263 in German, 172 in French and 14 in Italian. Of the total sample, 339 identified as mental health professionals, 81 as relatives and 29 as users. Considering the whole sample, almost half favored a name-change with a significant difference between stakeholder- and between language groups. Also, the name 'schizophrenia' was evaluated more critically than the diagnostic concept. Qualitative analysis of freetext answers showed a highly heterogenous argumentation, but no difference between language groups., Conclusions: Our results suggest the attitude towards re-naming might itself be subject to (micro)cultural difference, and they highlight the nature of 'schizophrenia' as not only a scientific, but also a linguistic and cultural object. Such local factors ought to be taken into consideration in the global debate., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest relating to the content of this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking., Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs])., Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022., Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes., Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias., Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs., Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies., Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US.

Background and Hypothesis: Racial discrimination and public stigma toward Black individuals living with schizophrenia create disparities in treatment-seeking and engagement. Brief, social-contact-based video interventions efficaciously reduce stigma. It remains unclear whether including racial identity experiences in video narrative yields greater stigma reduction. We hypothesized that we would replicate findings showing sustained stigma reduction in video-intervention groups vs control and that Black participants would show greater stigma reduction and emotional engagement than non-Black participants only for a racial-insights video presenting a Black protagonist., Study Design: Recruiting using a crowdsourcing platform, we randomized 1351 participants ages 18-30 to (a) brief video-based intervention, (b) racial-insights-focused brief video, or (c) non-intervention control, with baseline, post-intervention, and 30-day follow-up assessments. In 2-minute videos, a young Black protagonist described symptoms, personal struggles, and recovery from schizophrenia, with or without mentioning race-related experiences., Study Results: A 3 × 3 ANOVA showed a significant group-by-time interaction for total scores of each of five stigma-related domains: social distance, stereotyping, separateness, social restriction, and perceived recovery (all P < .001). Linear mixed modeling showed a greater reduction in stigma from baseline to post-intervention among Black than non-Black participants in the racial insights video group for the social distance and social restriction domains., Conclusions: This randomized controlled trial replicated and expanded previous findings, showing the anti-stigma effects of a brief video tailored to race-related experiences. This underscores the importance of personalized, culturally relevant narratives, especially for marginalized groups who, more attuned to prejudice and discrimination, may particularly value identification and solidarity. Future studies should explore mediators/moderators to improve intervention efficacy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Latinxs are vastly underrepresented in mental health research; one of many contributing factors may be complexities in the research consent process, including language preferences. We examined determinants of comprehension of research consent procedures and tested the effects of a preconsent research schema condition among 180 adults with schizophrenia (60 Latinx-English and 60 Latinx-Spanish preference, and 60 non-Latinx White)., Study Design: Participants were randomly assigned (equal allocation) to an educational session regarding clinical research concepts and processes (schema condition) or to an attention control. Following a subsequent simulated consent procedure for a hypothetical drug trail, comprehension of consent disclosures was measured with 2 standard measures., Study Results: One-way ANOVAs showed significant medium effect size differences between ethnicity/language groups on both measures of comprehension (η2s = 0.066-0.070). The Latinx-Spanish group showed lower comprehension than non-Latinx White participants; differences between the 2 Latinx groups did not reach statistical significance. Group differences were not statistically significant after adjusting for differences in education, or on scores from structured measures of acculturation, health literacy, or research literacy. Two-way ANOVAs showed no significant main effects for consent procedure on either comprehension measure (Ps > .369; partial η2s < 0.006) and no significant group-by-consent interactions (Ps > .554; partial η2s < 0.008)., Conclusions: Although the preconsent procedure was not effective, the results suggest health and research literacy may be targets for reducing disparities in consent comprehension. The onus is on researchers to improve communication of consent information as an important step to addressing health care disparities., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2023.)

Background: While there is increasing recognition of disparities in healthcare for Black Americans, there have been no comparisons in a nationally representative U.S. sample of Black and White adults with clinical diagnoses of schizophrenia., Methods: Using nationally representative survey data from the National Epidemiologic Survey on Alcohol and Related Conditions-III, we compared Black (n = 240, 36.2%) and White (n = 423, 63.8%) adults who report having been told by a physician that they have schizophrenia. Due to the large sample size, effect sizes (risk ratios and Cohen's d), rather than p-values, were used to identify the magnitude of differences in sociodemographic and clinical characteristics, including experiences of discrimination and service use. Multivariate analyses were used to identify independent factors., Results: Black individuals with diagnoses of schizophrenia reported multiple sociodemographic disadvantages, including lower rates of employment, educational attainment, income, marriage, and social support, with little difference in incarceration, violent behavior, and quality of life. They reported much higher scores on a general lifetime discrimination scale (Cohen's d = 0.75) and subscales representing job discrimination (d = 0.85), health system discrimination (d = 0.70), and public race-based abuse (d = 0.55) along with higher rates of past year alcohol and drug use disorders, but lower rates of co-morbid psychiatric disorders. Multivariable-adjusted regression analyses highlighted the independent association of Black race with measures of discrimination and religious service attendance; less likelihood of receiving psychiatric treatment (p = 0.02) but no difference in substance use treatment., Conclusion: Black adults with schizophrenia report numerous social disadvantages, especially discrimination, but religious service attendance may be an important social asset., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Previous research demonstrated an increase in the reporting of schizophrenia diagnoses among nursing home (NH) residents after the Centers for Medicare & Medicaid Services National Partnership to Improve Dementia Care. Given known health and healthcare disparities among Black NH residents, we examined how race and Alzheimer's and related dementia (ADRD) status influenced the rate of schizophrenia diagnoses among NH residents following the partnership., Methods: We used a quasi-experimental difference-in-differences design to study the quarterly prevalence of schizophrenia among US long-stay NH residents aged 65 years and older, by Black race and ADRD status. Using 2011-2015 Minimum Data Set 3.0 assessments, our analysis controlled for age, sex, measures of function and frailty (activities of daily living [ADL] and Changes in Health, End-stage disease and Symptoms and Signs scores) and behavioral expressions., Results: There were over 1.2 million older long-stay NH residents, annually. Schizophrenia diagnoses were highest among residents with ADRD. Among residents without ADRD, Black residents had higher rates of schizophrenia diagnoses compared to their nonblack counterparts prior to the partnership. Following the partnership, Black residents with ADRD had a significant increase of 1.7% in schizophrenia as compared to nonblack residents with ADRD who had a decrease of 1.7% (p = 0.007)., Conclusions: Following the partnership, Black NH residents with ADRD were more likely to have a schizophrenia diagnosis documented on their MDS assessments, and schizophrenia rates increased for Black NH residents with ADRD only. Further work is needed to examine the impact of "colorblind" policies such as the partnership and to determine if schizophrenia diagnoses are appropriately applied in NH practice, particularly for black Americans with ADRD., (© 2021 The American Geriatrics Society.)

Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5-1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 - β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy., (© 2021. The Author(s).)

Background: Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns., Methods: We used case-control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20-F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data., Results: Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69-2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31-1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22-1.89) and linguistic distance (OR 1.22, 95% CI 0.95-1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively., Conclusion: Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.

Schizophrenia is a severe psychiatric disorder with a strong hereditary component that affects approximately 1% of the world's population. The disease is most likely caused by the altered expression of a number of genes that function at the level of biological pathways or gene networks. Transcription factors (TF) are indispensable regulators of gene expression. EGR3 is a TF associated with schizophrenia. In the current study, DNA microarray and ingenuity pathway analyses (IPA) demonstrated that EGR3 regulates Reelin signaling pathway in SH-SY5Y cells. ChIP and luciferase reporter studies confirmed that EGR3 directly binds to the promoter region of RELN thereby activating RELN expression. The expression of both EGR3 and RELN was decreased during neuronal differentiation induced by retinoic acid (RA) in SH-SY5Y cells, and EGR3 over-expression reduced neurite outgrowth which could be partially reversed by the knockdown of RELN. The expression levels of EGR3 and RELN in peripheral blood of subjects with schizophrenia were found to be down-regulated (compared with healthy controls), and were positively correlated. Furthermore, data mining from public databases revealed that the expression levels of EGR3 and RELN were presented a positive correlation in post-mortem brain tissue of subjects with schizophrenia. Taken together, this study suggests that EGR3 is a novel TF of the RELN gene and regulates neurite outgrowth via the Reelin signaling pathway. Our findings contribute to the understanding of the regulatory role of EGR3 in the pathophysiology and molecular mechanisms of schizophrenia, and potentially to the development of new therapies and diagnostic biomarkers for the disorder., (© 2020 International Society for Neurochemistry.)

Abstract: Primarily we aimed to examine the crude and standardized schizophrenia hospitalization trend from 2005 to 2014. We hypothesized that there will be a statistically significant linear trend in hospitalization rates for schizophrenia from 2005 to 2014. Secondarily we also examined trends in hospitalization by race/ethnicity, age, gender, as well as trends in hospitalization Length of Stay (LOS) and inflation adjusted cost.In this observational study, we used Nationwide Inpatient Sample data and International Classification of Diseases, Eleventh Revisions codes for Schizophrenia, which revealed 6,122,284 cases for this study. Outcomes included crude and standardized hospitalization rates, race/ethnicity, age, cost, and LOS. The analysis included descriptive statistics, indirect standardization, Rao-Scott Chi-Square test, t-test, and adjusted linear regression trend.Hospitalizations were most prevalent for individuals ages 45-64 (38.8%), African Americans were overrepresented (25.8% of hospitalizations), and the gender distribution was nearly equivalent. Mean LOS was 9.08 days (95% confidence interval 8.71-9.45). Medicare was the primary payer for most hospitalizations (55.4%), with most of the costs ranging from $10,000-$49,999 (57.1%). The crude hospitalization rates ranged from 790-1142/100,000 admissions, while the US 2010 census standardized rates were 380-552/100,000 from 2005-2014. Linear regression trend analysis showed no significant difference in trend for race/ethnicity, age, nor gender (P > .001). The hospitalizations' overall rates increased while LOS significantly decreased, while hospitalization costs and Charlson's co-morbidity index increased (P < .001).From 2005-2014, the overall US hospitalization rates significantly increased. Over this period, observed disparities in hospitalizations for middle-aged and African Americans were unchanged, and LOS has gone down while costs have gone up. Further studies addressing the important disparities in race/ethnicity and age and reducing costs of acute hospitalization are needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Schizophrenia (SCZ) is a destructive neuropsychiatric illness affecting millions of people worldwide. The correlation between RELN gene polymorphisms and SCZ was investigated by previous researches, though the results remained conflicting. Based on the available studies, we conducted this meta-analysis to provide a more comprehensive outcome on whether the RELN gene polymorphisms (rs7341475 and rs262355) are associated with SCZ. A total of 15 studies with 25,403 subjects (9047 cases and 16,356 controls) retrieved from PubMed, ScienceDirect, EMBASE, Wiley, BMC, Cochrane, Springer, MDPI, SAGE, and Google Scholar up to June 2020 were included. Meta-analysis was performed using Review Manager 5.3. The heterogeneity was checked using I 2 statistics and Q-test, whereas publication bias was also measured. The rs7341475 polymorphism showed a significantly lower risk for SCZ for the allele (A vs. G: OR = 0.93, 95%CI = 0.87-0.99), codominant 1 (AG vs. GG: OR = 0.92, 95%CI = 0.85-0.99), dominant model (AA+AG vs. GG: OR = 0.92, 95%CI = 0.86-0.98), and over dominant model (AG vs. AA+GG: OR = 0.92, 95%Cl = 0.86-0.99). The allele, codominant model 1, and dominant models remained statistically significant after the correction of the Bonferroni (p < 0.025). Subgroup analysis confirmed the association of allele and dominant models in the Caucasian after Bonferroni correction. For rs262355 polymorphism, a significantly increased risk of SCZ was found only in Caucasians for codominant 2, dominant, and allele models, but significance exists only for the allele model after Bonferroni correction. Publication bias was found in the case of codominant 2 and recessive models for rs7341475 in the overall population, but this publication was not found after performing the Bonferroni correction or after performing the subgroup analysis. No such publication was found for rs262355. The results suggest that RELN rs7341475 is associated with a lower risk of SCZ in the overall population and Caucasian population, but rs262355 is associated with an increased risk of SCZ only in the Caucasian population.

Background: Persons of African ancestry are thought to carry a higher risk for extrapyramidal syndromes (EPS) in schizophrenia., Aim: We investigated the phenomenon of spontaneous and treatment-emergent EPS in a sample comprising Xhosa (South Africa) and Yoruba (Nigeria) Africans with first-episode schizophrenia and first exposure to antipsychotics., Methods: The Extrapyramidal Symptom Rating Scale (ESRS) and a variety of validated tools were used for the assessment of participants before, and two-weekly after treatment with low dose flupenthixol decanoate. Participants were followed up for 12 months. Association of EPS with clinical characteristics was investigated using Pearson's correlation and linear regression analyses., Results: Of 88 participants at baseline, 16 (18.1%) had at least one definite EPS prior to antipsychotic exposure and 34 (38.6%) had treatment-emergent EPS. While spontaneous Parkinsonism was associated with negative symptoms ( r  = 0.2, p  = 0.043; β  = 0.6, p  = 0.043), treatment-emergent EPS demonstrated non-significant correlations with clinical characteristics. Apart from dyskinesia, the frequency of treatment-emergent EPS decreased over 12 months observation., Conclusion: These findings support the hypothesis suggesting that spontaneously occurring Parkinsonism in schizophrenia may be the motor spectrum of negative symptomatology. Future studies of this relationship may lead to early identification of patients who may be more sensitive to EPS.

Accumulating evidence suggests that epigenetics plays an important role in the etiology of schizophrenia. Here, we performed a methylome-wide association study (MWAS) of first-onset schizophrenia patients and controls from the Han Chinese population using microarray technology. The DNA methylation profiles revealed 4494 differentially methylated CpG sites. Gene ontology (GO) analysis showed that the functions of differentially methylated genes were primarily involved in enzymatic activity, cytoskeleton organization and cell adhesion, and the TNIK (encoding TRAF2- and NCK-interacting kinase) gene was enriched in most of these terms. By combining the MWAS results with those of previous genome-wide association studies (GWASs), we identified 72 candidate genes located in 49 human genome loci. Among the overlapping genes, the most significantly methylated CpG sites were in the transcriptional start site (TSS) 200 region (cg21413905, P unadjusted  = 3.20 × 10 -5 ) of TNIK. TNIK was listed in the top 50 differentially methylated loci. The results of pyrosequencing and TNIK mRNA expression were consistent with those of the microarray study. Bioinformatics analyses, dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) studies showed that TNIK interacted with genes associated with schizophrenia and NRF1 was identified as a novel transcription factor (TF) that binds to TNIK in its TSS200 region. Thus, the regulatory function of NRF1 may be influenced by the status of the methylated CpG site in this region. In summary, our study provides new insights into the epigenetic mechanisms that regulate schizophrenia. Studies of the functions of TNIK methylation should be performed in vitro and in vivo to provide a better understanding of the pathophysiology of schizophrenia., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: Previous studies and meta-analysis indicated that rs1344706 was associated with schizophrenia in European population, whereas the conclusions in other populations were disputed. To further explore whether the allele A of rs1344706 would increase the risk of schizophrenia in different populations and update the original meta-analysis, we conducted a systematic review and meta-analysis worldwide., Methods: A literature search was performed in PubMed, Embase, Cochrane Library, PsycINFO and Web of Science (up to 10 July 2019) according to the inclusion criteria., Results: A total of 27 articles were included. Our meta-analysis showed an association between rs1344706 and schizophrenia in total populations [P = 0.000; odds ratio (OR) = 1.105; 95% confidence interval (CI), 1.048-1.165], Europe population (P = 0.025; OR = 1.108; 95% CI, 1.013-1.222) and Asian population(P = 0.005; OR = 1.094; 95% CI, 1.027-1.164)., Conclusions: Our findings suggested that the risk of single nucleotide polymorphism rs1344706 A-allele may increase the risk of schizophrenia worldwide. Also, this ethnicity-dependent effects of ZNF804A variant on schizophrenia may be related to the opposite allele direction. But to elucidate the underlying biological mechanism, further studies with large participant populations are needed., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Recent advances in functional genomics have facilitated the identification of multiple genes and isoforms associated with the genetic risk of schizophrenia, yet the causal variations remain largely unclear. A previous study reported that the schizophrenia risk single-nucleotide polymorphism (SNP) rs7085104 at 10q24.32 was in high linkage disequilibrium (LD) with a human-specific variable number of tandem repeat (VNTR), and both were significantly associated with the brain mRNA expression of a human-unique AS3MTd2d3 isoform in Europeans and African Americans. In this study, we have shown the direct regulation of the AS3MTd2d3 mRNA expression by this VNTR through an in vitro minigene splicing assay, suggesting that it is likely a causative functional variation. Intriguingly, we have further confirmed that the VNTR and rs7085104 are significantly associated with AS3MTd2d3 mRNA expression in brains of Han Chinese donors, and rs7085104 is also associated with risk of schizophrenia in East Asians. Finally, the overexpression of AS3MTd2d3 in cultured primary hippocampal neurons results in significantly reduced densities of mushroom dendritic spines, implicating its potential functional impact. Considering the crucial roles of dendritic spines in neuroplasticity, these results reveal the potential regulatory impact of the schizophrenia risk VNTR on AS3MTd2d3 and provide insights into the underlying biological mechanisms., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Schizophrenia is a complex disease with a putative genetic background. It was hypothesized that impaired mitochondrial function due to genetic alterations in mitochondrial DNA (mtDNA) could contribute to neurological conditions, including mental disorders. The aim of the study was to find out possible pathogenic mutations and/or variants in mtDNA potentially related to schizophrenia development., Objective: The study involved 37 patients with paranoid schizophrenia, whose mtDNA profiles were compared to those of 23 healthy controls., Methods: Patients and controls were assessed using PANSS (Positive and Negative Syndrome Scale) and General Health Questionnaire (GHQ), respectively. The entire mtDNA was sequenced by the NGS platform (MiSeq®, Illumina). Bioinformatics data were processed by mtDNA Variant Processor and Analyser (Illumina), mtDNA-Server, and SPSS-17., Results: A total of 480 mtDNA variants (single nucleotide replacements, point insertions, and deletions) were found. The polymorphic variant m.1811A>G (MT-RNR2) showed the highest frequency in schizophrenia (24.3%), as compared to the controls (4.3%) (p=0.07). Increased frequency was also found mainly in polymorphisms, belonging to complex 1 genes: MT-ND4 (11251G and 11467G), MT-ND3 (10398G), MT-ND1 (4216С), and MT-ND5 (12611G and 13708А), some of which were associated with mitochondrial dysfunction. Two individual mutations were identified in the patients: a pathogenic one - m.11778 A>G (LHON) and a newly identified, potentially pathogenic - m.4115 Т>C (NADH dehydrogenase 1)., Conclusion: Particular mtDNA variants predominantly in complex I, probably serve as a risk genetic background in schizophrenia. The presence of pathogenic mutations in patients with psychotic manifestations expands the clinical scope of mitochondrial diseases and deserves further investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Genomic studies on schizophrenia (SCZ) have revealed several candidate genes involved in excitatory synapse function and plasticity associated with its etiology. SHANK2 is a postsynaptic scaffolding protein, which anchors a protein complex connecting NMDAR, AMPAR, and mGluR receptors at excitatory neuronal synapses. Mutations in the SHANK2 gene have been reported to be associated with human autism spectrum disorders (ASDs) and SCZ. To identify variants in the SHANK2 gene and determine the association of SHANK2 with SCZ in the Chinese Uygur population, we conducted targeted sequencing of whole exon regions and exon-intron boundaries of SHANK2 in 1574 SCZ patients and 1481 healthy controls. A total of 149 variants were identified, including six common variants and 143 rare variants. For common variants, rs62622853 and rs3924047 showed allelic significance with SCZ before correction, but the association was eliminated after Bonferroni correction. Seven rare nonsynonymous variants, p.Arg739Trp, p.Pro807Leu, p.Ile854Phe, p.Thr1322Ser, p.Leu1434Arg, p.Val1486Ile, and p.Thr1674Met, occurred only in the patients but not in any of the healthy controls. In silico analysis predicted that p.Arg739Trp, p.Leu1434Arg, and p.Val1486Ile variants are likely to be damaging. The present study suggests that individuals with two novel rare nonsynonymous variants (p.Arg739Trp, p.Leu1434Arg) and p.Val1486Ile variants of SHANK2 might increase the susceptibility to developing SCZ disorder.

Previous studies have indicated associations between several OLIG2 gene single-nucleotide polymorphisms (SNPs) and susceptibility to schizophrenia among Caucasians. Consistent with these findings, postmortem brain and diffusion tensor imaging studies have indicated that the schizophrenia-risk-associated allele (A) in the OLIG2 SNP rs1059004 predicts lower OLIG2 gene expression in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients and reduced white matter (WM) integrity of the corona radiata in normal brains among Caucasians. In an effort to replicate the association between this variant and WM integrity among healthy Japanese, we found that the number of A alleles was positively correlated with WM integrity in some fiber tracts, including the right posterior limb of the internal capsule, and with mean blood flow in a widespread area, including the inferior frontal operculum, orbital area, and triangular gyrus. Because the A allele affected WM integrity in opposite directions in Japanese and Caucasians, we investigated a possible association between the OLIG2 gene SNPs and the expression level of OLIG2 transcripts in postmortem DLPFCs. We evaluated rs1059004 and additional SNPs in the 5' upstream and 3' downstream regions of rs1059004 to cover the broader region of the OLIG2 gene. The 2 SNPs (rs1059004 and rs9653711) had opposite effects on OLIG2 gene expression in the DLPFC in Japanese and Caucasians. These findings suggest ethnicity-dependent opposite effects of OLIG2 gene SNPs on WM integrity and OLIG2 gene expression in the brain, which may partially explain the failures in replicating associations between genetic variants and psychiatric phenotypes among ethnicities., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Migrants diagnosed with schizophrenia are overrepresented in forensic-psychiatric clinics. A comprehensive characterization of this offender subgroup remains to be conducted. The present exploratory study aims at closing this research gap. In a sample of 370 inpatients with schizophrenia spectrum disorders who were detained in a Swiss forensic-psychiatric clinic, 653 different variables were analyzed to identify possible differences between native Europeans and non-European migrants. The exploratory data analysis was conducted by means of supervised machine learning. In order to minimize the multiple testing problem, the detected group differences were cross-validated by applying six different machine learning algorithms on the data set. Subsequently, the variables identified as most influential were used for machine learning algorithm building and evaluation. The combination of two childhood-related factors and three therapy-related factors allowed to differentiate native Europeans and non-European migrants with an accuracy of 74.5% and a predictive power of AUC = 0.75 (area under the curve). The AUC could not be enhanced by any of the investigated criminal history factors or psychiatric history factors. Overall, it was found that the migrant subgroup was quite similar to the rest of offender patients with schizophrenia, which may help to reduce the stigmatization of migrants in forensic-psychiatric clinics. Some of the predictor variables identified may serve as starting points for studies aimed at developing crime prevention approaches in the community setting and risk management strategies tailored to subgroups of offenders with schizophrenia.

The relationships between stigma and quality of life in schizophrenia (QoL) have been extensively explored but have mostly focused on self-stigma and self-esteem and have never been explored in Latin-America. The objective of this study was to determine which stigma dimensions were associated with QoL in a sample of community-dwelling SZ subjects of three Latin-American countries. Stabilized outpatients with SZ were recruited in three Mental Health Services in three Latin-American countries: Bolivia (N = 83), Chile (N = 85) and Peru (N = 85). Stigma and Qol-SZ were evaluated by self-administered questionnaires, the Internalized Stigma of Mental Illness scale (ISMI-12) and the SQoL-18. 253 participants were included. In multivariate analyses, QoL has been associated with each stigma dimension (social stigma, stigma experience and self-stigma), independently of age, gender, education level, ethnicity, age at illness onset, illness symptomatology and mental health treatment. More specifically, social stigma was significantly associated with impaired psychological and physical well-being, self-esteem and friendship. Self-stigma was significantly associated with impaired psychological well-being, self-esteem and autonomy. The present results confirm the importance of stigma in QoL of SZ subjects and identify new targets to develop stigma-orientated programs. Most of the previous programs have focused on self-stigma while social stigma has shown to be associated with a wide range of impaired QoL areas. Stigma and QoL may have a bidirectional relationship and targeting some specific QoL areas (like autonomy through self-empowerment approaches) may also improve the effectiveness of these programs to reduce stigma impact on the quality of life of subjects with schizophrenia. Future studies should also explore differences across countries as subjects from Bolivia were more frequently Aymara and reported higher stigma and lower QoL than SZ subjects from other countries.

Background: Improving education level was evidenced to decrease the risk of schizophrenia, but whether this strength of education role depends on gender is not. This study aimed to investigate whether there was gender difference in the association between education and schizophrenia in Chinese adults., Methods: Data were obtained from the Second China National Sample Survey on Disability in 2006, including 1,909,205 participants aged 18 years or older. Schizophrenia was ascertained according to the International Statistical Classification of Diseases, Tenth Revision. Logistics regression models were fitted to examine the combined effect of gender and education on schizophrenia., Results: The lifetime prevalence of schizophrenia in female groups was higher than in male groups, with 0.44% (95%CI: 0.42-0.45%) and 0.36% (95%CI: 0.35-0.37%), respectively. Compared with schizophrenia male patients, more females with schizophrenia experienced severe or extreme difficulty in understanding and communicating. However, more males with schizophrenia suffered from severe or extreme difficulty in the function of daily activities. The combined effect of education and schizophrenia was statistically significant, indicating that, as the level of education increased, schizophrenia risk of females decreased faster than the risk of males., Conclusions: This study showed that additional years of education associated with lower risk of schizophrenia, and this association was stronger in females than in males. As education elevated, the risk of schizophrenia decreased more for women than for men. The findings indicate that improving education level may have an effect on reducing the gender disparities in mental health of China. Actions to prevent schizophrenia and address its gender disparities will require attention to the improving educational opportunities.

Background: The nature of the association between obstetric complications (OCs) at birth and the genetic aetiology of schizophrenia remains unclear, as some authors suggest that it is an independent risk factor while others support either interactionism or an epiphenomenon perspective., Objective: To examine the association of family history of schizophrenia (FHS) with history of OCs, with a view to assessing whether this relationship moderates clinical phenotypes such as symptom dimensions and age at onset of illness., Methods: This study examined OCs among schizophrenia probands using the Obstetric Complications Scale. An inquiry into family history was performed using the Family history method. Psychopathological symptom dimensions were assessed using standard scales. Data were analyzed to examine the interaction of FHS and history of OCs with age at onset and symptom dimensions, using ANCOVA., Results: FHS was significantly associated with the disorganized symptoms dimension (p=0.03). History of OCs was significantly associated with earlier age at onset (p=0.007). However, in ANCOVA, the effect of the interaction between FHS and history of OCs was not significant for age at onset and symptom dimensions (P = 0.059)., Conclusion: FHS was significantly associated with disorganization syndrome, and OCs was significantly associated with age at onset., (© 2020 Onu JU et al.)

Introduction: Theory of mind (ToM) has been established as one of the most investigated and pronounced social cognitive deficits in schizophrenia. Yet, knowledge on whether measures of ToM can be used and compared across cultures is sparse. In this study, we used two simple, non-verbal ToM tests in patients with schizophrenia and non-clinical controls from China and Denmark to investigate whether culture has an impact on ToM performance. Methods: Sixty-six patients with schizophrenia (35 Chinese) and 67 matched non-clinical controls (38 Chinese) from China and Denmark were tested with Brünés Picture Sequencing Task and Animated Triangles Task. We compared three models for each outcome variable in order to investigate which model best fitted the data: the first model included group (controls, patients) as a predictor variable, the second included group and nationality (Chinese, Danish), and the third included both predictors and their interaction. Results: On most ToM subtests, culture seemed to play a role. Only performance on Brüne's 1st order ToM were best described as similar in both countries. The second model had the best fit for most of the subtests indicating that the difference between patients and controls in China and Denmark, respectively, is similar. Conclusions: Caution to cultural differences should be taken when comparing ToM in Asian and Western patients with schizophrenia as well as healthy individuals.

Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in Asian countries. This study investigated clozapine prescription patterns and their associated factors in Asian countries and territories based on the database of the Research on Asian Psychotropic prescription study (REAP) conducted in 2016. Demographic and clinical information of 3744 schizophrenia patients in 15 Asian countries and territories was collected with a standardized data collection form. In total, 18.4% of the sample received clozapine, ranging from 2.6% in Japan to 32.3% in Hong Kong. Binary logistic regression analysis revealed that higher antipsychotic dose (OR = 1.002, P < 0.001), less frequent first admission in the sample (OR = 0.6, P < 0.001), more severe negative symptoms (OR = 1.4, P = 0.001) and less first generation antipsychotics (FGAs) (OR = 0.2, P < 0.001) were independently and significantly associated with clozapine prescription. Clozapine is frequently and increasingly prescribed for schizophrenia in Asia, with large variation across countries and territories. Given the diverse prescription patterns of clozapine found in Asian countries/territories, the clinical rationale of clozapine prescription needs careful consideration in Asia with more local input., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The genetic etiology of schizophrenia (SCZ) overlaps with that of other major psychiatric disorders in samples of European ancestry. The present study investigated transethnic polygenetic features shared between Japanese SCZ or their unaffected first-degree relatives and European patients with major psychiatric disorders by conducting polygenic risk score (PRS) analyses., Methods: To calculate PRSs for 5 psychiatric disorders (SCZ, bipolar disorder [BIP], major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder) and PRSs differentiating SCZ from BIP, we utilized large-scale European genome-wide association study (GWAS) datasets as discovery samples. PRSs derived from these GWASs were calculated for 335 Japanese target participants [SCZ patients, FRs, and healthy controls (HCs)]. We took these PRSs based on GWASs of European psychiatric disorders and investigated their effect on risk in Japanese SCZ patients and unaffected first-degree relatives., Results: The PRSs obtained from European SCZ and BIP patients were higher in Japanese SCZ patients than in HCs. Furthermore, PRSs differentiating SCZ patients from European BIP patients were higher in Japanese SCZ patients than in HCs. Interestingly, PRSs related to European autism spectrum disorder were lower in Japanese first-degree relatives than in HCs or SCZ patients. The PRSs of autism spectrum disorder were positively correlated with a young onset age of SCZ., Conclusions: These findings suggest that polygenic factors related to European SCZ and BIP and the polygenic components differentiating SCZ from BIP can transethnically contribute to SCZ risk in Japanese people. Furthermore, we suggest that reduced levels of an ASD-related genetic factor in unaffected first-degree relatives may help protect against SCZ development., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Neuroinflammation has been considered to be involved in the development of schizophrenia. This study aimed to study circulating autoantibodies for inflammatory cytokines in first-episode schizophrenia. A total of 181 patients and 197 controls were recruited for detection of plasma IgG antibodies against peptide antigens derived from interleukin 1α (IL1α), IL1ß, IL6, IL8 and tumour necrosis factor alpha (TNFα). The major finding was that patients with schizophrenia had significantly higher levels of anti-IL1ß IgG, anti-IL6 IgG and anti-IL8 IgG, and a significantly lower level of anti-IL1α IgG. This study suggests that inflammatory response may contribute to the development of schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Public stigma against psychiatric disorders leads to delayed treatment utilization and worsens treatment outcome. This study analyses the impact of expectations regarding the course of illness and attribution as medical illness on the desire for social distance towards schizophrenia and depression in Vietnam., Methods: In 2013, a survey (n = 771) using unlabelled vignettes either depicting a person with symptoms typical for schizophrenia or major depression was carried out in Hanoi. All respondents had to indicate whether the person was suffering from a medical illness or not. As an indicator of public stigma, the desire for social distance was measured. A possible correlation between expectations towards the course of illness and social distance was evaluated using a linear regression model., Results: 85 % of respondents endorsed that the person depicted in the schizophrenia vignette had a mental illness, compared to only 60 %, who were confronted with the depression vignette. This attribution of mental illness was correlated with higher levels of desire for social distance only in the schizophrenia vignette. While in the case of schizophrenia negative prognostic perceptions were associated with more desire for social distance, in the event of depression, it was only the expectation of lifelong dependency. Moreover, only for depression, positive expectations towards the course of illness correlated with less desire for social distance., Conclusion: These results indicate an impact of prognostic expectations on the desire for social distance and support strategies that aim at maintaining social integration and strengthening autonomy., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning the research, authorship, or publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Illness perceptions have been associated with patients' reactions to health threats and further health outcomes. The Illness Perception Questionnaire for Schizophrenia (IPQS) 1 has been applied in different contexts. However, the validity and reliability of IPQS remain unknown in mainland China., Aims and Objectives: To test the psychometric properties of the Chinese version of IPQS in mainland China., Design: A cross-sectional survey., Methods: A total of 200 community-dwelling patients with schizophrenia were surveyed in Beijing, China. The validity and reliability of the instrument were tested. As well as demographic data, the IPQS and the Knowledge About Schizophrenia Test (KAST) 2 were also administered., Results: Factor analysis was utilised to refine the factor structure of the IPQS. The difference between IPQS and KAST denoted the discriminant validity. The subscale scores among patients of different illness duration, educational attainment, and medication adherence in the past two years were significantly different (P＜0.05), indicating the known-group validity of the IPQS. Except for 'personal control' and 'burdensome effect', other subscales were internally consistent. Most of the subscales proved stable over a four-week period., Conclusion: The Chinese version of IPQS can be used, with some refinements, to assess illness perceptions about schizophrenia for patients in future studies. This will provide empirical evidence for its generalizability and clinical utility and provide deeper insight into Chinese patients' illness perceptions about schizophrenia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The calcium-binding protein S100b is secreted by glial cells in the brain and is also expressed by melanocytes. In nanomolar concentrations, S100b is considered to be a neurotrophic factor, but in micromolar concentrations, it is thought to reflect CNS injury and inflammation. Seen as a potential biomarker in traumatic brain injury, meta-analytic data from several studies report that S100b levels are significantly higher in persons with long standing schizophrenia, but also among first-episode patients compared to healthy control subjects. However, ethnic or racial differences are typically not mentioned when reporting levels of S100b. We assessed serum S100b levels in persons with schizophrenia (n = 136) who were participants in two independent research studies using the same enzyme-linked immunoassay (ELISA). African-American subjects had significantly higher levels of S100b (41.9 pg/ml ± 62.2) than Caucasian subjects (24.9 pg/ml ± 45.4) in the combined dataset (Mann-Whitney U = 1307, p < 0.001), as well as in each independent study. There were no significant differences in S100b levels between men and women. No significant correlations were observed between S100b levels and demographic or clinical variables. These data suggest that ethnicity or race should be given serious consideration when studying and interpreting S100b levels in persons with schizophrenia.

Purpose: To investigate association of two single nucleotide polymorphisms (SNPs) ABCB1(rs1045462) and DRD3(rs6280) with clozapine response and the dose in treatment resistant schizophrenia (TRS) patients., Methods: 200 TRS patients were enrolled in the study during their follow up visit post clozapine initiation. SNP assessment was performed for DRD3 (rs6280) and ABCB1(rs1045462) by sequencing. Blood sample for genotyping was collected with disease and treatment related variables recording on case record form. Patients were classified as responders or nonresponders based upon Andreasen criteria and Positive and Negative Syndrome Scale (PANSS)., Results: Mean clozapine dose, the genotype frequency distribution of ABCB1, DRD3 SNPs were significantly different in clozapine responder and non-responder study population (p < 0.05). CT genotype of ABCB1 and AG genotype of DRD3 were observed to be more prevalent in the responder group. TT genotype of ABCB1 and AG genotype of DRD3 were prevalent in the nonresponder group. Clozapine dosing equations for responder and nonresponder TRS populations were developed through logistic regression analysis. 27% variability in clozapine dose was explained by possible combinations of ABCB1 and DRD3 SNP analysis., Conclusion: Differential ABCB1(rs1045462) and DRD3(rs6280) genotype frequencies among the clozapine responders and non-responders explained clear feasibility of response predictor potential along with clozapine dose variability association. Pharmacogenetically guided clozapine dosing is possible if more SNPs are considered together with ABCB1(rs1045462) and DRD3(rs6280) in TRS patients., Competing Interests: Declaration of Competing Interest None declared, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

This study examined the joint influence of defendant race (Black/White) and mental disorder type (schizophrenia/depression) on mock juror decisions in a Not Guilty by Reason of Insanity (NGRI) case. We reasoned that unwillingness to vote for insanity would be more pronounced for a Black defendant with schizophrenia, given overlapping dangerousness and criminality stereotypes associated with those groups. Online community participants (N = 216) read a fictional second-degree murder case in which we varied mental disorder type and defendant race, then provided a verdict (guilty/NGRI) and answered questions regarding the trial. In line with hypotheses, participants were significantly more likely to vote guilty for a Black defendant with schizophrenia as compared to depression, but there were no significant differences for the White defendant. Results of this study suggest that bias in insanity trials can be exacerbated for a racialized defendant., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Although excess risks particularly for a diagnosis of schizophrenia have been identified for ethnic minority people in England and other contexts, we sought to identify and synthesise up-to-date evidence (2018) for affective in addition to non-affective psychoses by specific ethnic groups in England., Methods: Systematic review and meta-analysis of ethnic differences in diagnosed incidence of psychoses in England, searching nine databases for reviews (citing relevant studies up to 2009) and an updated search in three databases for studies between 2010 and 2018. Studies from both searches were combined in meta-analyses allowing coverage of more specific ethnic groups than previously., Results: We included 28 primary studies. Relative to the majority population, significantly higher risks of diagnosed schizophrenia were found in Black African (Relative risk, RR 5.72, 95% CI 3.87-8.46, n = 9); Black Caribbean (RR 5.20, 95% CI 4.33-6.24, n = 21); South Asian (RR 2.27, 95% CI 1.63-3.16, n = 14); White Other (RR 2.24, 95% CI 1.59-3.14, n = 9); and Mixed Ethnicity people (RR 2.24, 95% CI 1.32-3.80, n = 4). Significantly higher risks for diagnosed affective psychoses were also revealed: Black African (RR 4.07, 95% CI 2.27-7.28, n = 5); Black Caribbean (RR 2.91, 95% CI 1.78-4.74, n = 16); South Asian (RR 1.71, 95% CI 1.07-2.72, n = 8); White Other (RR 1.55, 95% CI 1.32-1.83, n = 5); Mixed Ethnicity (RR 6.16, 95% CI 3.99-9.52, n = 4)., Conclusions: The risk for a diagnosis of non-affective and affective psychoses is particularly elevated for Black ethnic groups, but is higher for all ethnic minority groups including those previously not assessed through meta-analyses (White Other, Mixed Ethnicity). This calls for further research on broader disadvantages affecting ethnic minority people.

Structural gray matter (GM) volume reductions in patients with schizophrenia have rarely been replicated across two different sites, the impact of culture and clinical characteristics remains unresolved. Hence, we assessed GM volume reductions in patients with schizophrenia using 3 T magnetic resonace imaging to replicate results across two independent and culturally different backgrounds (Germany, Japan), and to investigate the impact of brain volume reductions on clinical characteristics. In total, 163 German (80 patients) and 203 Japanese (83 patients) participants were included in the analysis. Voxel-based morphometry (VBM) was used to investigate structural differences between the groups and across the two sites, comparing local GM volumes. Clinical variables were used to analyze effects unrelated to the socio-cultural background. Across both data sets, widespread GM reductions in frontal and temporal cortical parts were found between patients and controls, indicating strong effects of diagnosis and only small effects of site. The investigation of clinical characteristics revealed the strongest effects for chlorpromazine equivalents on GM volume reductions primarily in the Japanese sample. Although the effects of site are small, several brain regions do not overlap between the two groups. Thus, GM may be affected differently at the two sites in patients with schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet., Methods: Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015., Results: The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²₁ = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (β = 0.75, t = 7.72, P < .001) and total score (β = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (β = 0.74, t = 8.45, P < .001), total score (β = 0.47, t = 5.71, P < .001), and cognitive factor subscore (β = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score., Conclusions: Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Background: We assessed whether the risk of various psychotic disorders and non-psychotic bipolar disorder (including mania) varied by migrant status, a region of origin, or age-at-migration, hypothesizing that risk would only be elevated for psychotic disorders., Methods: We established a prospective cohort of 1 796 257 Swedish residents born between 1982 and 1996, followed from their 15th birthday, or immigration to Sweden after age 15, until diagnosis, emigration, death, or end of 2011. Cox proportional hazards models were used to model hazard ratios by migration-related factors, adjusted for covariates., Results: All psychotic disorders were elevated among migrants and their children compared with Swedish-born individuals, including schizophrenia and schizoaffective disorder (adjusted hazard ratio [aHR]migrants: 2.20, 95% CI 1.96-2.47; aHRchildren : 2.00, 95% CI 1.79-2.25), affective psychotic disorders (aHRmigrant1.42, 95% CI 1.25-1.63; aHRchildren: 1.22 95% CI 1.07-1.40), and other non-affective psychotic disorders (aHRmigrant: 1.97, 95% CI 1.81-2.14; aHRchildren: 1.68, 95% CI 1.54-1.83). For all psychotic disorders, risks were generally highest in migrants from Africa (i.e. aHRschizophrenia: 5.24, 95% CI 4.26-6.45) and elevated at most ages-of-migration. By contrast, risk of non-psychotic bipolar disorders was lower for migrants (aHR: 0.58, 95% CI 0.52-0.64) overall, and across all ages-of-migration except infancy (aHR: 1.20; 95% CI 1.01-1.42), while risk for their children was similar to the Swedish-born population (aHR: 1.00, 95% CI 0.93-1.08)., Conclusions: Increased risk of psychiatric disorders associated with migration and minority status may be specific to psychotic disorders, with exact risk dependent on the region of origin.

Rationale: As a species, humans are vulnerable to numerous mental disorders, including depression and schizophrenia. This susceptibility may be due to the evolution of our large, complex brains, or perhaps because these illnesses counterintuitively confer some adaptive advantage. Additionally, cultural and biological factors may contribute to susceptibility and variation in mental illness experience and expression. Taking a holistic perspective could strengthen our understanding of these illnesses in diverse cultural contexts., Objectives: This paper reviews some of these potential factors and contextualizes mental disorders within a biocultural framework., Results: There is growing evidence that suggests cultural norms may influence inflammation, neurotransmitters, and neurobiology, as well as the illness experience. Specific examples include variation in schizophrenia delusions between countries, differences in links between inflammation and emotion between the United States and Japan, and differences in brain activity between Caucasian and Asian participants indicating that cultural values may moderate cognitive processes related to social cognition and interoception., Conclusions: Research agendas that are grounded in an appreciation of biocultural diversity as it relates to psychiatric illness represent key areas for truly interdisciplinary research that can result in culturally sensitive treatments and highlight possible biological variation affecting medical treatment.

Recent studies imply that rare variants contribute to the risk of schizophrenia, however, the exact variants or genes responsible for this condition are largely unknown. In this study, we conducted whole genome sequencing (WGS) of 20 Chinese families. Each family consisted of at least two affected siblings diagnosed with schizophrenia and at least one unaffected sibling. We examined functional variants that were found in affected sibling(s) but not in unaffected sibling(s) within a family. Matching this criterion, a frameshift heterozygous deletion of CA (-/CA) at chromosome 18:24722722, also referred to as rs752084147, in the Carbohydrate Sulfotransferase 9 (CHST9) gene, was detected in two families. This deletion was confirmed by PCR-based Sanger sequencing. With the observed frequency of 0.00076 in Han Chinese population, we performed both case-control and family-based analyses to evaluate its association with schizophrenia. In the case-control analyses, Chi-square test P-value was 6.80e-12 and the P-value was 0.0008 after one million simulations. In family-based segregation analyses, segregation P-value was 7.72e-7 and simulated P-value was 5.70e-6. For both the case-control and family-based analyses, the CA deletion was significantly associated with schizophrenia in the Chinese population. Further investigation of this gene  is warranted in the development of schizophrenia by utilizing larger and more ethnically diverse samples.

Background: Cross-cultural studies find that culture shapes people's understanding of mental illnesses, particularly Depression and Schizophrenia., Aims: To compare individuals' beliefs and attitudes toward Depression and Schizophrenia in Russia and the United States., Method: Participants ( N =607) were presented with vignettes of two diagnostically unlabeled psychiatric case histories and then answered questions regarding mental health literacy (MHL) and attitudes toward the person and the illness., Results: Our findings indicate that Depression was most often attributed to psychosocial stress while Schizophrenia was thought to be caused by biological factors. People from both countries considered those suffering from Schizophrenia to be unpredictable and dangerous. US participants were more likely to endorse lay and professional help for both disorders than their Russian counterparts. Russian participants reported being less likely to turn to someone they trust and more likely to deal with problems on their own. Russian participants were also more likely to view those with Depression as 'weak-willed' and leading an 'immoral lifestyle'., Conclusion: Our findings further inform cultural understandings of these mental illnesses in an often neglected national group. Patterns suggest that both groups may benefit from exposure to corrective information about Depression and Schizophrenia.

Cognitive insight refers to a person's ability to examine their psychotic experiences and the inferences they draw from these experiences. Several studies suggest that cultural factors influence cognitive insight and the processes involved therein; a few studies have suggested differences between Western and Asian societies. However, there are no studies on cognitive insight and its neural correlates in non-Western populations. Hence, we examined factor structure of Beck's cognitive insight scale (BCIS) in a large sample of patients with schizophrenia (SCZ) and healthy volunteers (HV) from India and assessed the relationship between cortical thickness and cognitive insight. We recruited 240 participants (SCZ-140; HV-100). Of these, 58 participants (SCZ-33; HV-25) underwent magnetic resonance imaging. We found a three-factor structure for BCIS which is different from the original two factor structure; self-reflection (SR) of original two-factor structure was sub-divided into- SR1, introspection and SR2, openness to feedback. There was a significant difference between HV and SCZ in the new factors, SR1 and SR2 but not in the original SR factor. Difference was also seen on MRI analysis; while there was a significant positive correlation between original SR factor and thickness of right posterior cingulate cortex, SR2 was positively correlated with thickness of left ventrolateral prefrontal cortex. The difference in factor structure in Indian participants and their distinct neural correlates point to cultural differences in cognitive insight. While in western societies the constructs of introspection and openness to feedback might integrate, they might be separate entities in Asian population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Compared with the majority population, those from minority ethnic groups in the UK are more likely to be admitted compulsorily during a first episode of psychosis (FEP). We investigated whether these disparities in pathways in to care continue., Methods: We analysed data from two first episode psychosis studies, conducted in the same geographical area in south London 15 years apart: the Aetiology and Ethnicity in Schizophrenia and Other Psychosis (AESOP) and the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) studies. The inclusion/exclusion criteria for case ascertainment for first episode psychosis were identical across the two studies. We performed multivariable logistic regression to estimate odds of compulsory admission by ethnic group, controlling for confounders., Participants: Two hundred sixty-six patients with first episode psychosis, aged 18-64 years, who presented to mental health services in south London in 1997-1999 and 446 with FEP who presented in 2010-2012., Results: When the two samples  were compared, ethnic differences in compulsory admission appear to have remained the same for black African patients, i.e. three times higher than white British in both samples: AESOP (adj. OR = 3.96; 95% CI = 1.80-8.71) vs. CRIS-FEP (adj. OR = 3.12; 95% CI = 1.52-6.35). Black Caribbean patients were three times more likely to be compulsorily admitted in AESOP (adj. OR = 3.20; 95% CI = 1.56-6.54). This was lower in the CRIS-FEP sample (adj. OR = 1.68; 95% CI = 0.71-3.98) and did not meet conventional levels for statistical significance., Conclusion: Ethnicity is strongly associated with compulsory admissions at first presentation for psychosis with evidence of heterogeneity across groups, which deserves further research.

Modeling dose-response relationships of drugs is essential to understanding their safety effects on patients under realistic circumstances. While intention-to-treat analyses of clinical trials provide the effect of assignment to a particular drug and dose, they do not capture observed exposure after factoring in nonadherence and dropout. We develop a Bayesian method to flexibly model the dose-response relationships of binary outcomes with continuous treatment, permitting multiple evidence sources, treatment effect heterogeneity, and nonlinear dose-response curves. In an application, we examine the risk of excessive weight gain for patients with schizophrenia treated with the second-generation antipsychotics paliperidone, risperidone, or olanzapine in 14 clinical trials. We define exposure as total cumulative dose (daily dose × duration) and convert to units equivalent to 100 mg of olanzapine (OLZ doses). Averaging over the sample population of 5891 subjects, the median dose ranged from 0 (placebo randomized participants) to 6.4 OLZ doses (paliperidone randomized participants). We found paliperidone to be least likely to cause excessive weight gain across a range of doses. Compared with 0 OLZ doses, at 5.0 OLZ doses, olanzapine subjects had a 15.6% (95% credible interval: 6.7, 27.1) excess risk of weight gain; corresponding estimates for paliperidone and risperidone were 3.2% (1.5, 5.2) and 14.9% (0.0, 38.7), respectively. Moreover, compared with nonblack participants, black participants had a 6.8% (1.0, 12.4) greater risk of excessive weight gain at 10.0 OLZ doses of paliperidone. Nevertheless, our findings suggest that paliperidone is safer in terms of weight gain risk than risperidone or olanzapine for all participants at low to moderate cumulative OLZ doses.

Worldwide, Schizophrenia Spectrum Disorder (SSD) affects a low percentage of individuals, but a severe health disparity exists for African-Americans, especially men. Several factors are contributing to this inequality. These factors occur at the individual, social, and organizational levels. With the other challenges facing African-Americans, SSD disparity is another shackle affecting this population. For health care providers, the challenges are treating a complex disorder in a hard to reach and stigmatized population. The purpose of this article is to provide an overview of the SSD disparity among African-Americans as identified in the literature and to discuss the role that Advanced Practice Nurses and other mental health providers have in reducing the disparity., Competing Interests: The author has no conflicts of interest to disclose., (Copyright© by the National Black Nurses Association, Inc.)

In recent years, large scale meta-analysis of genome-wide association studies (GWAS) have reliably identified genetic polymorphisms associated with neuropsychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD). However, the majority of disease-associated single nucleotide polymorphisms (SNPs) appear within functionally ambiguous non-coding genomic regions. Recently, increased emphasis has been placed on identifying the functional relevance of disease-associated variants via correlating risk polymorphisms with gene expression levels in etiologically relevant tissues. For neuropsychiatric disorders, the etiologically relevant tissue is brain, which requires robust postmortem sample sizes from varying genetic backgrounds. While small sample sizes are of decreasing concern, postmortem brain databases are composed almost exclusively of Caucasian samples, which significantly limits study design and result interpretation. In this review, we highlight the importance of gene expression and expression quantitative loci (eQTL) studies in clinically relevant postmortem tissue while addressing the current limitations of existing postmortem brain databases. Finally, we introduce future collaborations to develop postmortem brain databases for neuropsychiatric disorders from Chinese and Asian subpopulations., (Published by Elsevier Ltd.)

The identification of biological markers for psychosis has an impact on its diagnosis, prognosis, and likelihood of treatment response. Tissue plasminogen activator (tPA) is involved in important functions such as synaptic plasticity, long-term potentiation and neurogenesis. Plasminogen activator inhibitor (PAI-1) is the most important inhibitor of tPA. Preliminary studies have shown that schizophrenia patients have lower tPA and higher PAI-1 levels than the general population. The association of tPA and PAI-1 abnormalities with psychotic spectrum disorders, however, remains elusive. Our primary objective was to assess the plasma levels of tPA and PAI-1 in patients experiencing acute psychotic episodes as compared to those in healthy controls. In this prospective case-control study, we collected peripheral blood samples from psychiatric inpatients and healthy age, gender and race-matched subjects and determined plasma levels of tPA and PAI-1 by enzyme-linked immune-absorbent assays. Plasma levels of PAI-1 in patients with schizoaffective disorder were significantly lower as compared to those in control subjects (P = 0.03). tPA was lower in cases as compared to controls although it did not reach statistical significance. Asian patients and controls had lower PAI-1 levels. Further, Asian patients with schizoaffective disorder had significantly lower PAI-1 level compared to Asian patients with schizophrenia. Our results indicate that patients with schizoaffective disorder have lower PAI-1 levels than those with schizophrenia, affective psychosis, and healthy controls. Further studies are warranted to explore the potential of PAI-1 as a biomarker for diagnosing schizoaffective disorder., (Copyright © 2019 Elsevier B.V. All rights reserved.)

WHAT IS KNOWN ON THE SUBJECT?: While there is no single definition of the concept of recovery for people with mental illness, hope has been recognized as a guiding principle; the belief that it is possible for a person to regain a meaningful life, despite serious mental illness. Little is known about the recovery process of women diagnosed with schizophrenia per se, with only six studies offering the woman's voice identified and these all having taken place in developed countries. No studies on this topic have been carried out in Sub-Saharan Africa, including Swaziland. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This study provides unique insight into what is important to Swazi women, diagnosed with schizophrenia, in their process of their recovery. Because of current trends in migration, the findings of this study may provide mental health professionals with a better understand of the needs of those from this particular Sub-Saharan country. The study discusses a range of issues affecting women including being labelled as mentally ill, stigma and discrimination, the importance of the sociocultural context of illness and positive attributes which promote women's recovery. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This study provides mental health practitioners with insights and understanding of the lives of women from a Sub-Saharan developing country. This will be helpful for better understanding of the context of mental illness both for practitioners supporting the development of services in such countries and for those working in Western countries with migrant populations., Abstract: INTRODUCTION: Globally, twenty-four million people live with schizophrenia, 90% living in developing countries. While most Western cultures recognize service user expertise within the recovery process, this is not evident in developing countries. In particular, Swazi women diagnosed with schizophrenia experience stigma from family, community and care providers, thus compromising their recovery process., Aim: This study aimed to explore the experiences and meanings of recovery for Swazi women living with schizophrenia., Methodology: Interpretive phenomenological analysis was used. Fifteen women were recruited from Swaziland National Psychiatric Hospital out-patients' department, and face-to-face interviews were conducted., Findings: Four super-ordinate themes were identified: (a) The emotionality of "illness of the brain"; (b) Pain! Living with the illness and with others; (c) She is mad just ignore her; and (d) Being better., Discussion: Discussion focuses on the findings of this study and a number of positive and negative implications emanating from them: labelling, stigma and the roles of family, culture and religious beliefs on the process of recovery., Implications for Practice: This study provides practitioners with insight into the importance of the sociocultural context of the lives of women diagnosed with schizophrenia and how, in understanding this, mental health care could be improved., (© 2019 John Wiley & Sons Ltd.)

The aim of the study is to explore the variation on patient's Quality of Life (QoL) across three Latin-Americans countries. The study included 253 stabilized outpatients with schizophrenia from three Mental Health Services in Bolivia (N = 83), Chile (N = 85) and Peru (N = 85). Patients' were assessed using Schizophrenia Quality of Life Questionnaire (SQoL18). We collected socio-demographic information and clinical data, while recognizing the cultural complexity/dynamics of each country, and the influence of cultural contexts on how people experience the health systems. There are differences in QoL according to each country. Peru reports better levels of QoL at the Total Score Index and in most of the dimensions of the SQoL18. Bolivia shows the lowest indicators of QoL, except, interestingly, for the Resilience dimension where it reaches the highest scores. Even when the studied regions in the three Latin American countries share several cultural characteristics, there are also some important differences between them on patients' QoL. Possible disparities at investment in mental health by the Governments of each country are discussed while possible influences of (inter)cultural contexts are taken into account.

Patients with psychosis exhibit subsyndromal depressive symptoms during the course of illness and yet the clinical correlates of these symptoms remain under-investigated. We aimed to investigate the clinical correlates of subsyndromal depression in psychosis including the extent to which they mediate commonly observed comorbid substance dependence. We developed a model of depression in a non-clinical sample recruited via Amazon's Mechanical Turk (N = 266), and confirmed that model in a locally recruited African-American clinical sample comprising psychotic and non-psychotic individuals (N = 256). Using scores from this model we tested: the strength of relationships between depressive symptomatology and positive, negative and disorganized symptoms in a range of psychotic disorders; whether depressive symptoms were higher in individuals with affective psychoses versus schizophrenia; and if depressive symptomatology mediated the relationship between psychosis and substance dependence. Subsyndromal depressive symptomatology was significantly higher in individuals with psychosis than without psychosis, but did not significantly differ between affective and non-affective psychotic groups. Depressive symptomatology was significantly related to positive (but not negative or disorganized) psychotic symptoms, and mediated the relationship between psychosis and substance dependence. The present study underlines the importance of assessing subsyndromal depression in patients with psychosis, and generates a number of testable predictions for future work. In particular, the examination of the relationships between comorbid psychopathology, namely depression and substance abuse, may improve insight into the neurobiology of psychosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)