BACKGROUND:There is limited information on the prevalence and profile of comorbid physical health conditions in persons with untreated psychotic disorder in countries of the Global South. AIM:To investigate the frequency of occurence and association of physical health indicators with untreated psychotic disorder in three diverse settings in the Global South. METHODS:Data were collected as part of the International Research Programme on Psychoses in Diverse Settings (INTREPID II), a population-based incidence and case-control study conducted in selected catchment areas in India, Nigeria, and Trinidad. Cases were aged 18-64 years with an untreated psychotic disorder diagnosed according to ICD 10 criteria. Control participants were matched for age, sex, and neighbourhood. Physical health measurements were acquired using the WHO STEPwise approach to non-communicable disease risk factors surveillance instrument (WHO STEPS). We estimated adjusted odds ratios (aOR) using unconditional logistic regression. RESULTS:We included 225, 209, and 212 case-control pairs, respectively in Kancheepuram (India), Ibadan (Nigeria), and Northern Trinidad. Among cases, we found marked variations in health behaviours and physical health indicators across settings. In case-control comparisons within settings, cases were more likely to report poor diet (aORs of 1.31 [Trinidad] to 3.70 [Ibadan]), current smoking (aORs of 2.21 [Kancheepuram] to 3.35 [Trinidad]), and physical inactivity (aORs of 0.23 [Ibadan] to 0.62 [Kancheepuram]). However, we found no strong evidence that indicators of cardiometabolic comorbidity were consistently more common among cases compared with controls (i.e.,cases across sites were less likely than controls to have high blood pressure (aORs of 0.65 [Ibadan] to 0.76 [Trinidad]) and to be overweight (aORs of 0.70 [Kancheepuram] and 0.85 [Trinidad]), but were more likely than controls to have diabetes (aOR 1.94) and raised C-reactive protein levels (aOR 2.31) in Ibadan. By contrast, cases were more likely than controls to be underweight in all sites (aORs of 1.76 [Trinidad] to 3.67 [Ibadan]). In Kencheepuram (aOR 1.60) and Ibadan (aOR 2.66), cases were more likely to have a positive blood test for infection. These findings were broadly similar after accounting for health behaviours. CONCLUSION:In three settings in the Global South, persons with untreated psychotic disorder were more likely to report poorer health behaviours, to be underweight, and experience more infections, possibly reflecting severe economic and social disadvantage in the settings of this study.

Familial factors have been studied to be an important risk factor for suicidal behaviour among young people. Within families, conflicts across generations have been found to have a significant impact on young people's mental health and wellbeing. This scoping review aimed to identify existing literature examining intergenerational conflicts and its association with suicidal behaviour among young people aged 10-24 years. English articles related to intergenerational conflicts, suicide, suicidal ideation, and suicidal behaviour in a familial context experienced by young people have been included. OVID, PubMed, and Scopus databases were searched using relevant search terms and articles were selected based on the inclusion and exclusion criteria. On database search, four articles met the inclusion criteria and four more were included based on cross-referencing. Overall, eight studies were including in the synthesis of results. Significant positive association between intergenerational conflicts and suicidal ideation and behaviour among adolescents and young adults has been elucidated from the scoping review. Age-specific differences have been noted in the experience of conflicts, with adolescents primarily facing conflicts related to academic performance and cell phone usage and older youth facing conflicts about financial independence and interpersonal relationships. Females have been found to experience more intergenerational conflict and higher associated distress than males.

BackgroundIntergenerational conflicts with parents or grandparents have been shown to have adverse effects on young people. Inevitably these conflicts influence the mental health and well-being of young people.AimsThe scoping review aimed to identify the extent of existing literature related to intergenerational conflicts in a familial context, including the factors associated with those conflicts and the interventions addressing intergenerational issues.MethodArticles across OVID, PubMed, and ERIC databases on intergenerational conflicts involving youth (10-24), parents, and/or grandparents were identified. The review is reported adhering to PRISMA-ScR guidelines.ResultsFrom 185 database articles, 43 studies met eligibility criteria, and 4 more were added via cross-referencing, totalling 47. They were grouped into pre-COVID, COVID-related studies, and intervention studies. Parent-child conflict significantly impacted youth mental health, particularly internalising and externalising behaviours. Besides examining the associations, the review addresses the intergenerational conflict in the purview of Gender and cultural differences. Also, a focus on Interventions designed to enhance intergenerational relationships and resolve conflicts was discussed.ConclusionsThis review illuminates the detrimental impact of intergenerational conflicts within familial dynamics on the mental well-being of young individuals. It also encompasses the distinct landscape of intergenerational conflicts during the COVID-19 pandemic.

Background: The relationship between genotype and phenotype is governed by numerous genetic interactions (GIs), and the mapping of GI networks is of interest for two main reasons: 1) By modelling biological robustness, GIs provide a powerful opportunity to infer compensatory biological mechanisms via the identification of functional relationships between genes, which is of interest for biological discovery and translational research. Biological systems have evolved to compensate for genetic (i.e., variations and mutations) and environmental (i.e., drug efficacy) perturbations by exploiting compensatory relationships between genes, pathways and biological processes; 2) GI facilitates the identification of the direction (alleviating or aggravating interactions) and magnitude of epistatic interactions that influence the phenotypic outcome. The generation of GIs for human diseases is impossible using experimental biology approaches such as systematic deletion analysis. Moreover, the generation of disease-specific GIs has never been undertaken in humans.Methods: We used our Indian schizophrenia case-control (case-816, controls-900) genetic dataset to implement the workflow. Standard GWAS sample quality control procedure was followed. We used the imputed genetic data to increase the SNP coverage to analyse epistatic interactions across the genome comprehensively. Using the odds ratio (OR), we identified the GIs that increase or decrease the risk of a disease phenotype. The SNP-based epistatic results were transformed into gene-based epistatic results.Results: We have developed a novel approach by conducting gene-based statistical epistatic analysis using an Indian schizophrenia case-control genetic dataset and transforming these results to infer GIs that increase the risk of schizophrenia. There were ∼9.5 million GIs with a p-value ≤ 1 × 10−5. Approximately 4.8 million GIs showed an increased risk (OR > 1.0), while ∼4.75 million GIs had a decreased risk (OR <1.0) for schizophrenia.Conclusion: Unlike model organisms, this approach is specifically viable in humans due to the availability of abundant disease-specific genome-wide genotype datasets. The study exclusively identified brain/nervous system-related processes, affirming the findings. This computational approach fills a critical gap by generating practically non-existent heritable disease-specific human GIs from human genetic data. These novel datasets can train innovative deep-learning models, potentially surpassing the limitations of conventional GWAS.

Background: Improving mental health literacy (MHL) can reduce stigma towards mental illness, decreasing delays in help-seeking for mental disorders such as psychosis. We aimed to develop and assess the impact of an interactive MHL intervention on stigma related mental health knowledge and behaviour (SRMHKB) among youth in two urban colleges in South India. Methods: Incorporating input from stakeholders (students, teachers, and mental health professionals), we developed a mental health literacy module to address SRMHKB. The module was delivered as an interactive session lasting 90 min. We recruited 600 (300 males; 300 females; mean age 19.6) participants from two city colleges in Chennai from Jan-Dec 2019 to test the MHL module. We assessed SRMHKB before the delivery of the MHL intervention, immediately after, and at 3 and 6 months after the intervention using the Mental Health Knowledge Schedule (MAKS) and Reported and Intended Behaviour Scale (RIBS). We used generalised estimating equations (GEE) to assess the impact of the intervention over time. Results: Compared to baseline, there was a statistically significant increase in stigma related knowledge and behaviour immediately after the intervention (coefficient=3.8; 95% CI: 3.5,4.1) and during the 3-month (coefficient=3.4; 95% CI: 3.0,3.7) and 6-month (coefficient=2.4; 95% CI: 2.0,2.7) follow-up. Conclusion: Preliminary findings suggest that a single 90-minute MHL interactive session could lead to improvements in SRMHKB among youth in India. Future research might utilise randomised controlled trials to corroborate findings, and explore how improvements can be sustained over the longer-term.

Background Schizophrenia (SCZ) is a common yet poorly understood mental illness with a strong genetic link. While large studies have identified some common genetic variations associated with SCZ, many genetic and environmental risk factors remain a mystery. This might be due to rare germline mutations with stronger effects. Whole-exome sequencing (WES) has been used to identify these rare de novo mutations (DNMs). This approach has successfully revealed risk genes for other brain disorders, but for SCZ, it has only pinpointed a few strong candidates so far. Large studies of diverse ancestry are needed to understand how these rare mutations contribute to the risk of developing SCZ. However, DNM studies have been predominantly conducted on European and East Asian ancestry. Here, we report the first SCZ DNM study of South Asian ancestry, specifically in an Indian population. To our knowledge, this is the largest DNM exome sequence study of any disorder in a South Asian population to date. Methods Our participating families were recruited primarily by the Schizophrenia Research Foundation (SCARF, Chennai) in hospitals, community care centres, and primary care clinics across Tamil Nadu, India, resulting in a > 97% Tamil ethnicity sample. We used standardised assessment tools, administered where necessary, in Tamil. Over 25 years, we have recruited > 2300 affected and unaffected family members in 370 trios and 285 quads. All trios consist of an affected proband and unaffected parents, and all quads consist of an affected proband and unaffected parents and one sibling. All samples were exome-sequenced at the Australian Translational Genomics Centre and analysed at the Queensland Brain Institute, Brisbane, Australia, with a target of 20x depth in at least 90% of the exome target. All reported DNMs showed strong genotype concordance in the initial call. We conducted exome burden, single gene and gene set DNM enrichment analyses. Results Our study population was refined to 273 quads and 316 trios following stringent quality control procedures. The quads were split into case and control trios, leading to 589 case trios and 273 control trios. We investigated SCZ susceptibility using three annotation categories (Protein truncated variants (PTV), PTVs and missense, and all coding DNMs) by evaluating the per-gene enrichment of DNMs in affected probands compared to the expected gene-level background mutation rate. The exome-wide significance threshold was set at p=9.3e-7 to correct for multiple testing. Notably, two genes surpassed this threshold, with the most significant association across all three tests reaching p=1.57e-11. There was no significant difference between the case DNM rate and the control DNM rate for exome burden. However, when we compared DNM rates against a DNM expectation model, there were significant differences in missense and PTV DNMs. When we examined the proportional enrichment of genes hit by DNMs in a specified gene set relative to control DNMs and the DNM model, it did not reveal any significant pathways associated with SCZ. Discussion Although DNMs demonstrated high concordance with genotype data, we have yet to validate them. We report on 862 case and control trios, the largest exome-wide SCZ study in a South Asian population. Some DNMs were present in multiple trios, which, once validated, would be prioritised for further investigation. Compared to other DNM studies, our study identified genes with exome-wide significance and high levels of exome burden, especially among all coding DNMs and PTVs.

BackgroundPhysical exercise can improve outcomes for people with first-episode psychosis (FEP). Co-designing physical exercise interventions with end users has the potential to enhance their acceptability, feasibility, and long-term viability. This study’s objective was to use experience-based co-design (EBCD) methodology to develop a physical exercise intervention for FEP, and pilot test it.MethodsThe study was conducted at the Schizophrenia Research Foundation’s FEP program in Chennai, India. Participants(N=36) were individuals with FEP and their caregivers, mental health professionals (MHPs, and physical training experts. EBCD methodology included one-to-one interviews, focus group discussions, joint conferences, and co-design workshops. Two instructional videos were developed. Twelve FEP patients engaged in physical exercise with help of the videos over three months. They were followed up through weekly phone calls and in-person interviews to capture data on regularity, frequency, location of exercise and comfort levels.ResultsSeveral touch points emerged from the interviews, focus groups and joint meetings including lack of motivation, knowledge about physical exercise; differing perspectives about physical exercise; limited resource and time constraints. Two instructional videos demonstrating activities for participants incorporated strategies that addressed these touch points. Pilot data indicated that participants engaged with the physical exercise intervention over 3 months.ConclusionThis was the first study to use co-design methodology to design a physical exercise intervention for first-episode psychosis. The intervention may have therefore been responsive to stakeholder needs and preferences. Results of this study highlight the potential of co-design in designing and adapting interventions. There is need for rigorous testing with larger samples.

AbstractBackgroundCannabis use has been linked to psychotic disorders but this association has been primarily observed in the Global North. This study investigates patterns of cannabis use and associations with psychoses in three Global South (regions within Latin America, Asia, Africa and Oceania) settings.MethodsCase–control study within the International Programme of Research on Psychotic Disorders (INTREPID) II conducted between May 2018 and September 2020. In each setting, we recruited over 200 individuals with an untreated psychosis and individually-matched controls (Kancheepuram India; Ibadan, Nigeria; northern Trinidad). Controls, with no past or current psychotic disorder, were individually-matched to cases by 5-year age group, sex and neighbourhood. Presence of psychotic disorder assessed using the Schedules for Clinical Assessment in Neuropsychiatry and cannabis exposure measured by the World Health Organisation Alcohol, Smoking and Substance Involvement Screening Test (ASSIST).ResultsCases reported higher lifetime and frequent cannabis use than controls in each setting. In Trinidad, cannabis use was associated with increased odds of psychotic disorder: lifetime cannabis use (adj. OR 1.58, 95% CI 0.99–2.53); frequent cannabis use (adj. OR 1.99, 95% CI 1.10–3.60); cannabis dependency (as measured by high ASSIST score) (adj. OR 4.70, 95% CI 1.77–12.47), early age of first use (adj. OR 1.83, 95% CI 1.03–3.27). Cannabis use in the other two settings was too rare to examine associations.ConclusionsIn line with previous studies, we found associations between cannabis use and the occurrence and age of onset of psychoses in Trinidad. These findings have implications for strategies for prevention of psychosis.

Translation of research findings to actual clinical practice, now called translational research, is critical in low-resource settings and countries. In India, we have very few centers offering research training and even fewer agencies funding mental health research. It was in this context that the Schizophrenia Research Foundation (SCARF) based in Chennai used many of the research findings and processes to improve clinic and community-based care of persons with mental disorders. Based on 40 years of our experience of working in the community, this article provides an overview of our major research projects and the ways in which the findings that emanated were used in the promotion of better care.

BACKGROUND:Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad. METHODS:Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18-64 with previously untreated psychotic disorders residing in each catchment area (May 2018-April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years). RESULTS:We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68-3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51-0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93-1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area. CONCLUSIONS:This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.

Importance Less than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the world. Objective To compare demographic and clinical profiles of cohorts of cases and rates of untreated psychoses (proxy for incidence) across and within 3 economically and socially diverse settings in the Global South. Two hypotheses were tested: (1) demographic and clinical profiles of cases with an untreated psychotic disorder vary across setting and (2) rates of untreated psychotic disorders vary across and within setting by clinical and demographic group. Design, Setting, and Participants The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II) comprises incidence, case-control, and cohort studies of untreated psychoses in catchment areas in 3 countries in the Global South: Kancheepuram District, India; Ibadan, Nigeria; and northern Trinidad. Participants were individuals with an untreated psychotic disorder. This incidence study was conducted from May 1, 2018, to July 31, 2020. In each setting, comprehensive systems were implemented to identify and assess all individuals with an untreated psychosis during a 2-year period. Data were analyzed from January 1 to May 1, 2022. Main Outcomes and Measures The presence of an untreated psychotic disorder, assessed using the Schedules for Clinical Assessment in Neuropsychiatry, which incorporate the Present State Examination. Results Identified were a total of 1038 cases, including 64 through leakage studies (Kancheepuram: 268; median [IQR] age, 42 [33-50] years; 154 women [57.5%]; 114 men [42.5%]; Ibadan: 196; median [IQR] age, 34 [26-41] years; 93 women [47.4%]; 103 men [52.6%]; Trinidad: 574; median [IQR] age, 30 [23-40] years; 235 women [40.9%]; 339 men [59.1%]). Marked variations were found across and within settings in the sex, age, and clinical profiles of cases (eg, lower percentage of men, older age at onset, longer duration of psychosis, and lower percentage of affective psychosis in Kancheepuram compared with Ibadan and Trinidad) and in rates of untreated psychosis. Age- and sex-standardized rates of untreated psychoses were approximately 3 times higher in Trinidad (59.1/100 000 person-years; 95% CI, 54.2-64.0) compared with Kancheepuram (20.7/100 000 person-years; 95% CI, 18.2-23.2) and Ibadan (14.4/100 000 person-years; 95% CI, 12.3-16.5). In Trinidad, rates were approximately 2 times higher in the African Trinidadian population (85.4/100 000 person-years; 95% CI, 76.0-94.9) compared with the Indian Trinidadian (43.9/100 000 person-years; 95% CI, 35.7-52.2) and mixed populations (50.7/100 000 person-years; 95% CI, 42.0-59.5). Conclusions and Relevance This analysis adds to research that suggests that core aspects of psychosis vary by historic, economic, and social context, with far-reaching implications for understanding and treatment of psychoses globally.

The interplay between genotype and phenotype is governed by a multitude of genetic interactions (GIs), and the mapping of GI networks holds significant importance for two main reasons: (1) GIs offer a valuable means to uncover compensatory biological mechanisms by modelling biological robustness, thereby identifying functional relationships between genes. This aspect is particularly relevant for biological exploration and translational research, as biological systems have evolved to compensate for genetic (i.e. variations, mutations) and environmental (i.e. drug efficacy) perturbations by leveraging compensatory relationships between genes, pathways, and biological processes; (2) GI facilitates the identification of the direction (positive/alleviating or negative/aggravating interactions) and magnitude of epistatic interactions that influence the resulting phenotype. While comprehensive GI databases exist for organisms like yeast, generating GIs for human diseases through experimental biology methods such as systematic deletion analysis is infeasible. Furthermore, generating disease-specific GIs in humans has not been previously attempted. We used the Indian schizophrenia case-control (case-816, controls-900) genetic dataset to implement and test GI workflow. Standard GWAS sample quality control procedure was followed to check for ancestry and relatedness outliers. We used the imputed genetic data to increase the SNP coverage to analyse epistatic interactions across the genome comprehensively. By using the odds ratio (OR) we identified the GIs that increase (OR >1) or decrease (OR < 1) the risk of a disease phenotype (i.e. schizophrenia). The SNP-based epistatic results were transformed into gene-based epistatic results. We have developed a GI workflow for conducting gene-based statistical epistatic analysis and transforming these results to infer GIs. Spatial analysis of functional enrichment (SAFE) was used to detect the statistically overrepresented functional groups. There were ∼ 9.5 million GIs with a p-value ≤ 1 × 10-4. Approximately 4.8 million GIs showed an increased risk (Odds Ratio > 1.0), while ∼ 4.75 million GIs had decreased/no risk (Odds Ratio < 1.0) for schizophrenia. We identified many hub genes with numerous GIs, which increased and reduced the risk of Schizophrenia. In contrast to model organisms, this approach is specifically viable in humans due to the availability of abundant disease-specific genome-wide genotype datasets. Despite limited power, meaningful GI data was generated with a small sample. SAFE and REVIGO analysis exclusively identified brain/nervous system-related processes, affirming the findings. This computational approach fills a critical gap by generating practically non-existent heritable disease-specific human GIs from human genetic data. These novel datasets can train innovative deep-learning models for post-GWAS functional characterisation, potentially surpassing the limitations of conventional GWAS.

Background/Objectives: People living with severe mental illness may be more susceptible to infection and stress, leading to relapses or worsening of their mental health. The experiences of people with severe mental illness during the coronavirus disease 2019 (COVID-19) pandemic have seldom been captured. This study set to describe the experience of people with severe mental illness in Tamil Nadu, India, during the COVID-19 pandemic. Methods: Between July and December 2020, 158 age-, gender-, neighborhood-matched case − control pairs from the INTREPID II study completed a survey regarding their experience, worries, and behavioral changes during the pandemic. Their responses were collected by phone during six-monthly check-ins, or in-person at 24-month follow-up appointments. Only the first response for each participant is included in this report. Results: None of our participants reported knowingly having been infected with COVID-19 by the time of the survey. There is no evidence that people with psychoses were disproportionately affected by the pandemic. Unemployment and financial hardship were highly prevalent in both cases and controls. Job-related anxiety and stress were the largest source of worry, followed by worries regarding government decisions and access to mobile phones. Conclusions: The pandemic placed great strain on participants both with and without severe mental illness. The impact of unemployment and financial hardship as a result of COVID-19 requires urgent attention.

This invited commentary identifies and elaborates on some quandaries in evolving a schizophrenia construct that mental health professionals from LAMI countries could face. These range from diagnosis, classification, genetics to other social issues. The views and explanatory models held by the community of persons with schizophrenia and their families compound this problem.

Psychosocial rehabilitation (PSR) is an important and essential component in the management of persons with severe mental disorders (SMD), along with pharmacological and psychological interventions. PSR is instrumental to bring positive change in the social and occupational functioning of persons with SMD by providing support and addressing their specific psychosocial needs. Here, we provide an overview of the various PSR strategies offered to persons with SMD as a part of the SCARF Telepsychiatry in Pudukkottai (STEP) program in the rural communities of Tamil Nadu. We undertook an analysis of the project data for the period 2010–2019 during which 14,496 individuals had received some intervention under the STEP program and the various PSR activities provided are listed. Our results indicate a range of PSR activities were provided to persons with SMD and their family members including facilitating the receipt of disability and welfare benefits, help with employment, obtaining loans from banks to start private small enterprises, to help with emergency and other admissions. Our experiences have been able to demonstrate that it is eminently possible to incorporate and integrate PSR interventions in community based programmes for persons with severe mental disorders.

BackgroundThere is evidence of an association between life events and psychosis in Europe, North America and Australasia, but few studies have examined this association in the rest of the world. AimsTo test the association between exposure to life events and psychosis in catchment areas in India, Nigeria, and Trinidad and Tobago. MethodWe conducted a population-based, matched case-control study of 194 participants in India, Nigeria, and Trinidad and Tobago. Cases were recruited through comprehensive population-based, case-finding strategies. The Harvard Trauma Questionnaire was used to measure life events. The Screening Schedule for Psychosis was used to screen for psychotic symptoms. The association between psychosis and having experienced life events (experienced or witnessed) was estimated by conditional logistic regression. ResultsThere was no overall evidence of an association between psychosis and having experienced or witnessed life events (adjusted odds ratio 1.19, 95% CI 0.62-2.28). We found evidence of effect modification by site (P = 0.002), with stronger evidence of an association in India (adjusted odds ratio 1.56, 95% CI 1.03-2.34), inconclusive evidence in Nigeria (adjusted odds ratio 1.17, 95% CI 0.95-1.45) and evidence of an inverse association in Trinidad and Tobago (adjusted odds ratio 0.66, 95% CI 0.44-0.97). ConclusionsThis study found no overall evidence of an association between witnessing or experiencing life events and psychotic disorder across three culturally and economically diverse countries. There was preliminary evidence that the association varies between settings.