Effectiveness of a mental health literacy module on stigma related mental health knowledge and behaviour among youth in two educational settings in Chennai, South India: A quasi-experimental study.

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.

Designing and implementing a physical exercise intervention for people with first episode psychosis using experience-based co-design: A pilot study from Chennai, India.

BACKGROUND: Physical 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. METHODS: The 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. RESULTS: Several 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. CONCLUSION: This 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.

Cannabis use and psychotic disorders in diverse settings in the Global South: findings from INTREPID II.

BACKGROUND: Cannabis 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. METHODS: Case-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). RESULTS: Cases 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. CONCLUSIONS: In 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.

Urbanicity and rates of untreated psychotic disorders in three diverse settings in the Global South.

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.

Epidemiology of Untreated Psychoses in 3 Diverse Settings in the Global South: The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II).

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.

Genetic interactions of schizophrenia using gene-based statistical epistasis exclusively identify nervous system-related pathways and key hub genes.

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.

Life events and psychosis: case-control study from India, Nigeria, and Trinidad and Tobago.

BACKGROUND: There 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. AIMS: To test the association between exposure to life events and psychosis in catchment areas in India, Nigeria, and Trinidad and Tobago. METHOD: We 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. RESULTS: There 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). CONCLUSIONS: This 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.

Schizophrenia construct: Quandaries and conundrums in India and LAMIC.

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.

Prevalence and risk factors of perinatal depression among women in rural Bihar: A community-based cross-sectional study.

BACKGROUND: Perinatal depression (PND) is one of the most common mental disorders occurring during the perinatal period among women. Few studies examined prevalence and risk factors of PND from rural settings in India. This study aimed to estimate the prevalence of perinatal depression and identify social risk factors for it among women from rural Bihar. MATERIALS AND METHODS: A cross sectional study was conducted in a community setting in rural areas of Bihar. All perinatal women were screened through a door to door survey and recruited after obtaining informed consent. A semi-structured proforma was used to collect sociodemographic characteristics and family related variables. Edinburgh postnatal depression scale (EPDS) was used to screen for perinatal depression. RESULTS: A total of 564 perinatal women were recruited into the study. The estimated prevalence of PND was 23.9 % (95 % CI: 20.6,27.6). Multivariate analysis showed perinatal depression was associated with physical illness in the mother, previous history of abortion, poor financial status and ill-treatment by in-laws. CONCLUSION: Prevalence of perinatal depression among women is high in rural settings of North India. A multitude of factors ranging from physical, obstetric, economic and family related confer a high risk for PND. Comprehensive interventions are needed to address these risk factors of perinatal depression.

Support groups for family caregivers of persons with dementia in India.

A caregiver support group was initiated at the Schizophrenia Research Foundation, Chennai, India. The study aimed to evaluate this service for 100 caregivers of persons with dementia, identify the needs met and explore the facilitating factors and barriers for participation. The support group met the information, emotional and counselling needs of caregivers. Trust between members was a key facilitating factor. Lack of help at home to support the person with dementia, distance from the venue and work commitments were barriers to caregiver participation. The study found that support groups fulfil an important need for caregivers by providing information and peer support.

A qualitative study on the use of mobile-based intervention for perinatal depression among perinatal mothers in rural Bihar, India.

BACKGROUND: Perinatal depression (PND) is one of the most common psychiatric illnesses in women, with a prevalence around 22% in India. Leveraging mobile-based technologies could help in the prevention and treatment of perinatal depression even in remote places. Understanding the experiences and barriers of using such technology interventions by perinatal mothers could help in the better design and in delivery of these interventions. We aimed to study the experiences of the perinatal women using a mobile phone-based intervention, Interactive Voice Response System (IVRS), for the prevention and management of perinatal depression in a rural district of Bihar, India. MATERIALS AND METHODS: A total of 12 in-depth interviews (IDIs) and one focus group discussion (FGD) with eight participants were conducted with perinatal mothers using the mobile-based IVRS to explore the experiences and perspectives of women receiving mobile phone-based interventions for the treatment of PND. Thematic analysis was done to identify major themes. RESULTS: Five major themes emerged from the study around accessibility, usability, community participation, cost and preference to either intervention. Women found the mobile-based intervention useful as it made them feel lighter. They considered mental health as a health issue and wanted help to address their problems. They became familiar with terms like anxiety, depression, helplessness and burden and bean using them in their conversations. The patients used therapeutic strategies such as breathing, coping and relaxation. They even agreed to take up sessions for their peer group. CONCLUSION: Women in rural Bihar seemed satisfied with the technology-based intervention. It has made mental health issues more visible and acceptable even in the rural hinterlands of Bihar.

Learnings from conducting mental health research during 2004 tsunami in Tamil Nadu, India.

BACKGROUND: The Indian Ocean tsunami experience in 2004 caused a major loss of life and subsequent emotional trauma for survivors. Psychosocial needs in the aftermath of this disaster were extensive, yet the cohesion and effectiveness of response were limited due to lack of preparedness and relevant policy. The Schizophrenia Research Foundation (SCARF) was one of the organizations that quickly responded to provide psychosocial assistance to people in the tsunami affected areas and recognized a need for relevant research on disaster response. Therefore, we undertook research on the challenges, success and limitations of psychosocial interventions in alleviating post-traumatic symptomology. DISCUSSION: Both community-level workers and researchers were limited in their preparedness to carry out tasks related to response. Language barriers, cultural differences, and a gap in long-term services limited the breadth and scope of research that was able to be completed. Lack of policy, poor co-ordination of services, lack of trained researchers and limited resources were challenges that emerged during this period and various strategies were adopted to meet these challenges. CONCLUSIONS: Continued research and evaluation of data has brought crucial considerations to light, including the variance in symptomology, effective tools of measurement, and the nuanced response of survivors. Future research should take relevant factors into consideration including barriers to care. Understanding of the local language and religious beliefs are significant resources in understanding the nature of survivors' trauma response and effective means of coping. Lastly, limitations regarding time frame and scope of research should be evaluated to provide more effective, comprehensive methods in future studies.

Association of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at amino acid level in individuals with schizophrenia: A study from South India.

BACKGROUND: Schizophrenia, a chronic severe psychiatric illness of unknown aetiology, has been shown to be associated with HLA alleles but at varied degree in different population. The present study has focussed on analysing the frequency of HLA class I and class II alleles in persons with schizophrenia from South India. METHODS: Ninety seven individuals with schizophrenia and 103 age- and gender-matched controls were typed for HLA- A, B, C, DRB1 and DQB1 loci by next-generation sequencing in Illumina MiniSeq using MIA FORA NGS FLEX HLA typing kit. RESULTS: The results showed that HLA-A*01:01:01, B*37:01:01 and C*01:02:01 were positively associated with schizophrenia while HLA-B*35:03:01 and DRB1*04:03:01 were negatively associated. Gender-specific associations revealed that DRB1*10:01:01 and DQB1*05:01:01 were positively associated while DQB1*03:02:01 was negatively associated with female subjects with schizophrenia. A*24:02:01~B*37:01:01~C*06:02:01~DRB1*10:01:01~DQB1*05:01:01 is the predominant haplotype in schizophrenia population when compared to healthy controls. Amino acid association in susceptible and protective alleles has shown that the presence of peptide in the peptide-binding groves of mature HLA-A protein (K, M, V, R and V at 44th, 67th, 150th, 156th and 158th position), HLA-B protein (D and S at 77th and 99th position) and HLA-C protein (M at 99th position) confer susceptibility to the disease, only in the absence of E (Glutamic acid) at 74th position in mature HLA-DRB1 protein. Interaction of amino acids in protective alleles namely B*35:01:01 and DRB1*04:03:01 has revealed that aspartic acid at 114th (D) position in mature HLA-B protein and glutamic acid (E) at 74th position of mature HLA-DRB1 protein have a combined effect in protecting against the disease. CONCLUSION: The study has revealed the HLA association with schizophrenia in south Indian population. The amino acid interaction with the disease needs to be confirmed in a larger population.

INTREPID II: protocol for a multistudy programme of research on untreated psychosis in India, Nigeria and Trinidad.

INTRODUCTION: There are few robust and directly comparable studies of the epidemiology of psychotic disorders in the Global South. INTREPID II is designed to investigate variations in untreated psychotic disorders in the Global South in (1) incidence and presentation (2) 2-year course and outcome, (3) help-seeking and impact, and (4) physical health. METHODS: INTREPID II is a programme of research incorporating incidence, case-control and cohort studies of psychoses in contiguous urban and rural areas in India, Nigeria and Trinidad. In each country, the target samples are 240 untreated cases with a psychotic disorder, 240 age-matched, sex-matched and neighbourhood-matched controls, and 240 relatives or caregivers. Participants will be followed, in the first instance, for 2 years. In each setting, we have developed and are employing comprehensive case-finding methods to ensure cohorts are representative of the target populations. Using methods developed during pilot work, extensive data are being collected at baseline and 2-year follow-up across several domains: clinical, social, help-seeking and impact, and biological. ETHICS AND DISSEMINATION: Informed consent is sought, and participants are free to withdraw from the study at any time. Participants are referred to mental health services if not already in contact with these and emergency treatment arranged where necessary. All data collected are confidential, except when a participant presents a serious risk to either themselves or others. This programme has been approved by ethical review boards at all participating centres. Findings will be disseminated through international conferences, publications in international journals, and through local events for key stakeholders.

Methodology for Development of a Community Level Intervention Module for Physical Illness in Persons with Mental Illness (CLIPMI).

BACKGROUND AND OBJECTIVES: Medical illnesses seen in persons with psychiatric disorders are important but often ignored causes of increased morbidity and mortality. Hence, a community level intervention program addressing the issue is proposed. MATERIALS AND METHODS: Patients with severe mental illnesses will be identified by a door-to-door survey and assessed for comorbid physical illnesses like anemia, hypertension, diabetes, and so on. They will then be randomized into two groups. The treatment as usual (TAU) group will not receive intervention from the trained community level workers, while the Intervention group will receive it. RESULTS: The two groups will be compared for the prevalence and severity of comorbid physical illnesses. The expected outcome is compared to the TAU group, the intervention group will have a greater reduction in the morbidity due to physical illnesses and improved mental health. CONCLUSION: If successful, the module can be incorporated into the community level mental health delivery system of the District Mental Health Program (DMHP).

What constitutes recovery in schizophrenia? Client and caregiver perspectives from South India.

BACKGROUND: Understanding the concept of recovery in severe mental illnesses such as schizophrenia from the social and cultural aspects is important as it will help in developing models of recovery and appropriate interventions. Client and caregiver perspectives on recovery play a significant role in shaping these models and interventions. Hence, the aim of this study was to understand how clients with schizophrenia and their caregivers perceive recovery and to examine the differences between male and female clients with schizophrenia. MATERIALS AND METHODS: A total of 100 clients with schizophrenia and 80 caregivers of clients with schizophrenia were included in the study after written informed consent. A semi-structured proforma was used to collect the sociodemographic profile and illness variables. A questionnaire was developed to assess the indicators of recovery from mental illness and was administered to study participants. Descriptive statistics including frequency and percentages were used along with the chi-square test for analysis. RESULTS: The most common indicators of recovery for the clients with schizophrenia were absence of symptoms (88%), no relapse (70%) and going back to work (70%), while for the caregivers were absence of symptoms (100%), becoming independent (92.5%) and no relapse (91%). Indicators of recovery were similar between male and female clients with schizophrenia except for the need to stop medication as an indicator of recovery observed significantly more in females (p = .006). Most clients used internal validation of indicators to assess their recovery (79%). CONCLUSION: Results indicate that clients and caregivers from India perceive recovery as being symptom free, able to go back to work and being independent. Clients with schizophrenia use internal validation to assess recovery. Gender does not play a role in the perceptions toward recovery in schizophrenia. These results will help in developing models of recovery for severe mental illness in Indian context leading to tailored interventions.

Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study.

Importance: Genome-wide association studies (GWASs) in European populations have identified more than 100 schizophrenia-associated loci. A schizophrenia GWAS in a unique Indian population offers novel findings. Objective: To discover and functionally evaluate genetic loci for schizophrenia in a GWAS of a unique Indian population. Design, Setting, and Participants: This GWAS included a sample of affected individuals, family members, and unrelated cases and controls. Three thousand ninety-two individuals were recruited and diagnostically ascertained via medical records, hospitals, clinics, and clinical networks in Chennai and surrounding regions. Affected participants fulfilled DSM-IV diagnostic criteria for schizophrenia. Unrelated control participants had no personal or family history of psychotic disorder. Recruitment, genotyping, and analysis occurred in consecutive phases beginning January 1, 2001. Recruitment was completed on February 28, 2018, and genotyping and analysis are ongoing. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms and gene expression with schizophrenia. Results: The study population included 1321 participants with schizophrenia, 885 family controls, and 886 unrelated controls. Among participants with schizophrenia, mean (SD) age was 39.1 (11.4) years, and 52.7% were male. This sample demonstrated uniform ethnicity, a degree of inbreeding, and negligible rates of substance abuse. A novel genome-wide significant association was observed between schizophrenia and a chromosome 8q24.3 locus (rs10866912, allele A; odds ratio [OR], 1.27 [95% CI, 1.17-1.38]; P = 4.35 × 10-8) that attracted support in the schizophrenia Psychiatric Genomics Consortium 2 data (rs10866912, allele A; OR, 1.04 [95% CI, 1.02-1.06]; P = 7.56 × 10-4). This locus has undergone natural selection, with the risk allele A declining in frequency from India (approximately 72%) to Europe (approximately 43%). rs10866912 directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex (normalized effect size, 0.79; 95% CI, 0.6-1.0; P = 5.8 × 10-13). NAPRT1 encodes a key enzyme for niacin metabolism. In Indian lymphoblastoid cell lines, (risk) allele A of rs10866912 was associated with NAPRT1 downregulation (AA: 0.74, n = 21; CC: 1.56, n = 17; P = .004). Preliminary zebrafish data further suggest that partial loss of function of NAPRT1 leads to abnormal brain development. Conclusions and Relevance: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene's role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenialike symptoms in neuropsychiatric diseases such as pellagra and Hartnup disease, these results suggest that the rs10866912 genotype and niacin status may have implications for schizophrenia susceptibility and treatment.

Objective psychosocial function vs. subjective quality-of-life in schizophrenia within 5-years after diagnosis: A study from southern India.

There is increasing interest from treaters and patients alike in subjective quality-of-life (sQOL) and objective psychosocial function as indices of treatment outcome in studies of schizophrenia. With the emergence of evidence-based treatment protocols (e.g., NIMH-funded Recovery after Initial Schizophrenia Episode Initiative) these outcomes are of particular significance in treatment studies of samples early in the course of their illness. Few studies have investigated demographic, clinical and cognitive factors associated with sQOL in samples early in the course of their illness and compared these factors to objective measures. We administered measures of sQOL or satisfaction with life, and objective psychosocial function to 59 people with schizophrenia within 5-years of diagnosis, along with standardized measures of symptoms and cognition. Results revealed that symptoms, rather than cognitive or demographic variables, were the best independent predictors of both subjective QOL and objective functioning. Positive symptoms were independent predictors of sQOL, while positive and negative symptoms were independent predictors of objective psychosocial status. Depression and cognition were also linked to sQOL. These findings point to the importance of attending to residual positive symptoms early in the treatment of schizophrenia as a means of possibly enhancing both subjective and objective outcome in early course schizophrenia.