Prevalence of Psychiatric Morbidity and Alcohol use Disorders Among Adolescent Indigenous Tribals from Three Indian States.

Background: Among the Indian adolescents, the prevalence of psychiatric morbidity and alcohol use disorders (AUD) are 7.3% and 1.3%. However, no separate data are available for indigenous tribal populations. This study estimated the prevalence of psychiatric morbidity and AUD and associated socio-demographic factors among adolescents in the tribal communities in three widely varying states in India. Methods: Using validated Indian versions of the MINI 6.0, MINI Kid 6.0, and ICD-10 criteria, we conducted a cross-sectional survey from January to May 2019 in three Indian sites: Valsad, Gujarat (western India); Nilgiris, Tamil Nadu (south India); and East Khasi Hills district of Meghalaya (north-east India) on 623 indigenous tribal adolescents. Results: Aggregate prevalence of any psychiatric morbidity was 15.9% (95% CI: 13.1-19.0) (males: 13.6%, 95% CI: 10.0-18.1; females: 17.9%, 95% CI: 13.9-22.6), with site-wise statistically significant differences: Gujarat: 23.8% (95% CI: 18.1-30.2), Meghalaya: 17.1% (95% CI: 12.4-22.7), Tamil Nadu: 6.2% (95% CI: 3.2-10.5). The prevalence of diagnostic groups was mood disorders 6.4% (n = 40), neurotic- and stress-related disorders 9.1% (n = 57), phobic anxiety disorder 6.3% (n = 39), AUD 2.7% (n = 17), behavioral and emotional disorders 2.7% (n = 17), and obsessive-compulsive disorder 2.2% (n = 14). These differed across the sites. Conclusion: The prevalence of psychiatric morbidity in adolescent tribals is approximately twice the national average. The most common psychiatric morbidities reported are mood (affective) disorders, neurotic- and stress-related disorders, phobic anxiety disorder, AUD, behavioral and emotional disorders, andobsessive-compulsive disorder.

Improving mental ill-health with psycho-social group interventions in South Asia-A scoping review using a realist lens.

This scoping review aimed to synthesise current evidence related to psycho-social groups as part of community-based mental health interventions in South Asia. We used a realist lens to pay attention to the contexts and mechanisms supporting positive outcomes. We included studies published from January 2007 to February 2022 that: were based in communities in South Asia, included a group component, reported on interventions with a clear psychosocial component, targeted adults and were implemented by lay community health workers. Two reviewers extracted data on intervention components, groups and facilitators, participant demographics and enabling contexts, mechanisms and outcomes. Expert reference panels including people with lived experience of psycho-social disability, mental health professionals and policy makers confirmed the validity and relevance of initial review findings. The review examined 15 interventions represented by 42 papers. Only four interventions were solely psycho-social and nearly all included psychoeducation and economic support. Only 8 of the 46 quantitative outcome measures used were developed in South Asia. In a context of social exclusion and limited autonomy for people with psychosocial disability, psychosocial support groups triggered five key mechanisms. Trusted relationships undergirded all mechanisms, and provided a sense of inclusion, social support and of being able to manage mental distress due to improved skills and knowledge. Over time group members felt a sense of belonging and collective strength meaning they were better able to advocate for their own well-being and address upstream social health determinants. This led to outcomes of improved mental health and social participation across the realms of intrapersonal, interpersonal and community. Psychosocial groups merit greater attention as an active ingredient in community interventions and also as an effective, relevant, acceptable and scalable platform that can promote and increase mental health in communities, through facilitation by lay community health workers.

Significance of an altered lncRNA landscape in schizophrenia and cognition: clues from a case-control association study.

Genetic etiology of schizophrenia is poorly understood despite large genome-wide association data. Long non-coding RNAs (lncRNAs) with a probable regulatory role are emerging as important players in neuro-psychiatric disorders including schizophrenia. Prioritising important lncRNAs and analyses of their holistic interaction with their target genes may provide insights into disease biology/etiology. Of the 3843 lncRNA SNPs reported in schizophrenia GWASs extracted using lincSNP 2.0, we prioritised n = 247 based on association strength, minor allele frequency and regulatory potential and mapped them to lncRNAs. lncRNAs were then prioritised based on their expression in brain using lncRBase, epigenetic role using 3D SNP and functional relevance to schizophrenia etiology. 18 SNPs were finally tested for association with schizophrenia (n = 930) and its endophenotypes-tardive dyskinesia (n = 176) and cognition (n = 565) using a case-control approach. Associated SNPs were characterised by ChIP seq, eQTL, and transcription factor binding site (TFBS) data using FeatSNP. Of the eight SNPs significantly associated, rs2072806 in lncRNA hsaLB_IO39983 with regulatory effect on BTN3A2 was associated with schizophrenia (p = 0.006); rs2710323 in hsaLB_IO_2331 with role in dysregulation of ITIH1 with tardive dyskinesia (p < 0.05); and four SNPs with significant cognition score reduction (p < 0.05) in cases. Two of these with two additional variants in eQTL were observed among controls (p < 0.05), acting likely as enhancer SNPs and/or altering TFBS of eQTL mapped downstream genes. This study highlights important lncRNAs in schizophrenia and provides a proof of concept of novel interactions of lncRNAs with protein-coding genes to elicit alterations in immune/inflammatory pathways of schizophrenia.

Subclinical psychotic symptoms in Indian adults: Application of the Community Assessment of Psychic Experiences (CAPE).

BACKGROUND: The study investigated the psychometric properties of the Community, Assessment of Psychic Experiences (CAPE-42), a self-report instrument in Indians. METHOD: CAPE-42 was translated in Hindi and tested on 312 Indian adults recruited online and through paper-pencil assessment. Confirmatory factor analysis (CFA) was employed to establish the factor structure of the positive, negative and depressive dimensions of CAPE-42: the bifactor model was tested to evaluate whether items converge into a major single factor defining psychotic-proneness in individuals. Latent class analysis (LCA) was conducted to identify subgroups with a different endorsement of subclinical psychotic symptoms. , RESULTS: CAPE-Hindi showed good reliability (Cronbach's alpha>0.80). CFA confirmed, a good fit for the bifactor model, factor loading was acceptable for all items in the general factor (Omega-h =0.83) and explained the primary variance of the subscales. Residual variance was explained by the positive, negative and depressive factors (Omega H =0.33, 0.04 and 0.12, respectively). LCA identified three classes traceable, to the three dimensions; a low endorsement group (n = 155; 50 %); a less consistent, group with endorsement on positive and depressive items (n = 117; 38 %), and a high, endorsement group (n = 40;13 %). CONCLUSION: Hindi CAPE-42 showed good reliability and factorial validity.

Association between thyroid functions, cognition, and functional connectivity of the brain in early-course schizophrenia: A preliminary study.

Background: The functional outcome of the debilitating mental illness schizophrenia (SZ) has an integral role in cognition. The thyroid hormone has a vital role in the developmental stages and functioning of the human brain. Aim: This study aimed to evaluate the relationship between thyroid functions, cognition, and functional imaging of the brain in persons with SZ. Materials and Methods: Sixty SZ (Diagnostic and Statistical Manual (DSM-5)) persons, aged 18-50 years of both genders, were recruited in this cross-sectional observational study. Positive and Negative Syndrome Scale (PANSS) and Trail Making Tests (TMTs) A and B were administered to all patients. To assess the level of thyroid hormone, a test was conducted. Functional connectivity of the brain was assessed using resting-state functional magnetic resonance imaging (rs-fMRI). Data analysis was performed by descriptive and analytical statistical methods. FSL version 5.9 (FMRIB's) software was used for analyses of fMRI neuroimages. Results: There were no significant differences between the two populations on sociodemographic factors. The average value for thyroid-stimulating hormone (TSH) in the hypothyroid group (n = 12) and the euthyroid group (n = 47) was 8.38 mIU/l and 2.44 mIU/l, respectively. The average time in seconds for TMT-A and TMT-B was 87.27 and 218.27 in the hypothyroid group and 97.07 and 293.27 in the euthyroid group, respectively. Similarly, in the sample matched on age, gender, and age at onset of illness, there were no significant differences in demographic and clinical factors and resting-state network (RSN) between the hypothyroid (N = 10) and euthyroid (N = 10) groups. Conclusion: No differences were found in the functional brain network between the hypothyroid and euthyroid groups as the study sample did not include clinically hypothyroid persons with SZ.

Ethical dilemmas encountered in suicide research and management: Experiences of young mental health professionals.

This study aimed to explore ethical dilemmas and challenges faced by young mental healthcare researchers and professionals working with survivors of suicide (hereinafter suicide survivors). Two focus group discussions (FGDs) Researcher FGD (with those engaged in suicide research) and Clinician FGD (with those providing treatment to suicide survivors) - consisting of open-ended questions and lasting for 70-90 minutes were conducted and analysed using Thematic Analysis. Five themes were identified: i) struggling with the incongruity of harm within benefit, ii) difficulty in delineating boundaries, iii) self-doubt in one's professional competence, iv) nature of suicide straining the limits of confidentiality, and v) working with structural limitations. The study helps to understand the obstacles and dilemmas encountered in adhering to ethical principles while working with vulnerable individuals.

Why Do People Live or Die? A Retrospective Study from a Crisis Intervention Clinic in North India.

Background: Suicide results from complex interactions of various risk factors-reasons for dying (RFD)-and protective factors-reasons for living (RFL). Suicide is not necessarily a wish to die but may be an appeal for help. We analyzed RFD and RFL in persons who had attempted suicide, through their clinical records at a Crisis Intervention Clinic (CIC). Methods: We retrospectively analyzed demographic and clinical data, and classified RFD and RFL, among patients with either ideas or attempt of suicide registered at our CIC (N = 83). Using two open-ended questions from the clinical history data, we derived their RFD or RFL; (n = 53) completed these questions regarding RFD-RFL. Results: In the total sample, males and females were equally represented and educated, but males were significantly older. Most common diagnosis was nonpsychotic mood disorder. Commonest mode of suicide attempt was hanging. Family conflict vs. family responsibility, hope vs. hopelessness, stressful life events, and negative cognitions about the self and the world were important RFD. RFL included feeling responsible, love for family and for self, hope, career success, and religious beliefs. Conclusion: RFD and RFL could both be grouped in similar categories related to family, career, hope, etc.

Genetic variations in evolutionary accelerated regions disrupt cognition in schizophrenia.

Cognition is believed to be a product of human evolution, while schizophrenia is ascribed as the by-product with cognitive impairment as it's genetically mediated endophenotype. Genomic loci associated with these traits are enriched with recent evolutionary markers such as Human accelerated regions (HARs). HARs are markedly different in humans since their divergence with chimpanzees and mostly regulate gene expression by binding to transcription factors and/or modulating chromatin interactions. We hypothesize that variants within HARs may alter such functions and thus contribute to disease pathogenesis. 49 systematically prioritized variants from 2737 genome-wide HARs were genotyped in a north-Indian schizophrenia cohort (331 cases, 235 controls). Six variants were significantly associated with cognitive impairment in schizophrenia, thirteen with general cognition in healthy individuals. These variants were mapped to 122 genes; predicted to alter 79 transcription factors binding sites and overlapped with promoters, enhancers and/or repressors. These genes and TFs are implicated in neurocognitive phenotypes, autism, schizophrenia and bipolar disorders; a few are targets of common or repurposable antipsychotics suggesting their draggability; and enriched for immune response and brain developmental pathways. Immune response has been more strongly targeted by natural selection during human evolution and has a prominent role in neurodevelopment. Thus, its disruption may have deleterious consequences for neuronal and cognitive functions. Importantly, among the 15 associated SNPs, 12 showed association in several independent GWASs of different neurocognitive functions. Further analysis of HARs may be valuable to understand their role in cognition biology and identify improved therapeutics for schizophrenia.

Feasibility, acceptability and evaluation of meditation to augment yoga practice among persons diagnosed with schizophrenia.

OBJECTIVE: To design a meditation protocol and test its feasibility, acceptability and efficacy in conjunction with yoga training (YT) for persons with schizophrenia (SZ). METHODS: The meditation protocol consisted of Anapana (observing normal respiration) and Yoga Nidra (supine, restful awareness). In a single-blind randomised controlled trial, medicated and clinically stable outpatients diagnosed with SZ were randomised to receive treatment as usual (TAU), TAU augmented with YT or TAU augmented with meditation and yoga training (MYT) for 3 weeks (N = 145). Acceptability, clinical, social and cognitive functions were assessed after 3-week and 3-month post-randomisation using within-group and between-group analyses with repeated measures multivariate tests. RESULTS: No group-wise differences in compliance, study discontinuation, major/serious side effects or adverse events were noted. For six assessed clinical variables, the direction of changes were in the desired direction and the effect sizes were greater in the MYT group compared with the TAU group at both time points. Changes in social function variables were greater at 3 months than at 3 weeks. Nominally significant improvement in individual cognitive domains were noted in all groups at both time points. All effect sizes were in the small to medium range. CONCLUSION: MYT is feasible and acceptable and shows modest benefits for persons with SZ. MYT can also improve quality of life and clinical symptoms. Larger studies of longer duration are warranted.

Stepped Care Model for Developing Pathways of Screening, Referral, and Brief Intervention for Depression in Pregnancy: A Mixed-Method Study from Development Phase.

Background: Depression in pregnancy affects nearly one in five women in low- and middle-income countries and is associated with adverse obstetric and neonatal outcome. Burden of morbidity is high, but specialized mental health resources are meager. Effective low intensity psychosocial interventions hold promise to fill the treatment gap for maternal depression. In this paper, we aim to describe the process of development of a stepped care model incorporating screening, providing brief intervention, and referral pathways developed for managing depression in pregnancy in antenatal care health facilities in India. Methodology: Using complex intervention development and evaluation method of Medical Research Council, United Kingdom, we searched evidence-based strategies from preexisting manuals, conducted formative research for need assessment and stakeholder engagement, and developed the intervention following an expert review panel. We conducted pilot testing to assess the feasibility and acceptability of intervention supplemented by three focused group discussions. Results: Manual review identified psychoeducation, empathetic listening, behavior activation, and supportive counseling as important elements. Need assessment revealed huge gap in perinatal mental health knowledge. Nearly 92% of total 272 perinatal women had poor awareness and 35%-70% of total 62 health-care providers had poor knowledge. In qualitative interview, women reported depressive symptoms as a normal part of pregnancy and had poor help seeking, behavior symptoms of depression were more prominent. A stepped care algorithm was developed for screening all expectant mothers in each trimester for depression using Patient Health Questionnaire-9 (PHQ-9). Women with PHQ-9 score >19 or reporting self-harm ideation were urgently referred to psychiatrist. Women with PHQ-9 score 5-19 were given brief intervention for depression in pregnancy intervention by antenatal nurse. The intervention developed consists of three sessions of psychoeducation, relaxation exercise, and mental health promotion, each lasting 20 min and at gap of 2 weeks each. Service providers and mothers reported good acceptability of psychosocial intervention and reported satisfaction with content and delivery of intervention. Conclusion: Low intensity brief psychosocial interventions can be adapted for implementation if relevant stakeholders are engaged at each step right from development of such as screening, intervention pathway to delivery, and effectiveness study.

A brief psycho-social intervention for COVID-19 vaccine hesitancy among perinatal women in low-and middle-income countries: Need of the hour.

COVID-19 vaccines are one of the most effective strategies for preventing COVID-19 infection, as well as the associated mortality and morbidity. Despite the availability of COVID-19 vaccines, vaccine acceptance among perinatal women is challenging in low and middle-income countries (LMICs). Further, the vaccine hesitancy among perinatal women may have an impact on their children's vaccinations. The purpose of this paper is to briefly discuss the existing research on COVID-19 and non-COVID-19 vaccine hesitancy, psychosocial aspects, measures, and the individual level interventions for vaccine hesitancy among perinatal women. In our opinion, there is a need for further research with a specific focus on developing effective and feasible individual-level interventions to address COVID-19 vaccine hesitancy among perinatal women in LMICs.

COVID-19 vaccine confidence project for perinatal women (CCPP)-Development of a stepped-care model to address COVID-19 vaccine hesitancy in low and middle-income countries.

Background: COVID-19 vaccine hesitancy (CVH) is common among perinatal women in low and middle-income countries (LMICs), but it is often unaddressed. This could be due to a lack of feasible, scalable, and acceptable interventions and models for CVH in LMICs. Our study aimed to develop a CVH intervention model that can be implemented in LMICs using existing human healthcare resources. Methods: A literature review was conducted on aspects of vaccine hesitancy, pre-existing interventions, and models for addressing vaccine hesitancy (COVID-19 and non-COVID-19). The lead authors (RR and PKuk) formed a team consisting of vaccinators, experts, and stakeholders. Members shared their perspectives and proposals for various models and interventions that could be implemented in LMICs. A CVH intervention model was developed using a logic model, a WHO implementation toolkit, experts' feedback, and consensus. Results: A consensus was reached to develop a COVID-19 Vaccine Confidence Project for Perinatal Women (CCPP), which is a primary health care worker (HCWs)-based stepped-care model. The CCPP model includes HCW training, integration into ongoing COVID-19 vaccination programs, CVH screening, CVH intervention, and referral services suitable for implementation in LMICs. Conclusion: The CCPP project/model provides a practical approach that can help in the early detection and management of CVH. The model can be tailored to different healthcare settings to improve COVID-19 vaccine uptake among perinatal women in LMICs.

A Randomized Controlled Trial to Assess Feasibility and Acceptability of Telephone-Based Psychosocial Interventions in Individuals who Attempted Suicide.

BACKGROUND: Brief contact interventions such as telephone-based contacts appear to be useful in individuals who attempted suicide. Most studies of telephone-based contacts in such individuals typically consisted of frequent phone reminders for adherence to treatment and seeking help for mental health issues. Telephone-based psychosocial interventions that incorporate elements of supportive and problem-solving strategies are of interest in Indian settings due to their potential application in mitigating the wide mental health gap. Feasibility studies of telephone-based psychosocial interventions could help ascertain the difficulties that arise in the implementation of such treatments. METHODS: A multicentric randomized controlled trial (RCT) is currently underway in general hospital settings in two Indian cities to study the efficacy of telephone-based psychosocial interventions in individuals with a recent suicide attempt, with routine telephone contacts (TCs) serving as the comparator. Prior to that RCT, this feasibility study was conducted to assess the acceptability of the telephone-based intervention and telephone contacts. Feasibility was assessed using dropout rates. Acceptability was assessed using participant-rated Likert-based visual analog scores from 0 to 10, with higher scores indicating greater acceptability. RESULTS: Dropout rates and mean acceptability scores for telephone-based psychosocial interventions were 38.5% and 8.63, while those for TCs were 41.7% and 7.57, respectively. CONCLUSIONS: Telephone-based psychosocial interventions are feasible and acceptable in individuals with a recent suicide attempt.

Measurement invariance of the Childhood Autism Rating Scale (CARS) across six countries.

The Childhood Autism Rating Scale (CARS) is a simple and inexpensive tool for Autism spectrum disorder (ASD) assessments, with evidenced psychometric data from different countries. However, it is still unclear whether ASD symptoms are measured the same way across different societies and world regions with this tool, since data on its cross-cultural validity are lacking. This study evaluated the cross-cultural measurement invariance of the CARS among children with ASD from six countries, for whom data were aggregated from previous studies in India (n = 101), Jamaica (n = 139), Mexico (n = 72), Spain (n = 99), Turkey (n = 150), and the United States of America (n = 186). We analyzed the approximate measurement invariance based on Bayesian structural equation modeling. The model did not fit the data and its measurement invariance did not hold, with all items found non-invariant across the countries. Items related to social communication and interaction (i.e., relating to people, imitation, emotional response, and verbal and nonverbal communication) displayed lower levels of cross-country non-invariance compared to items about stereotyped behaviors/sensory sensitivity (i.e., body and object use, adaptation to change, or taste, smell, and touch response). This study found that the CARS may not provide cross-culturally valid ASD assessments. Thus, cross-cultural comparisons with the CARS should consider first which items operate differently across samples of interest, since its cross-cultural measurement non-invariance could be a source of cross-cultural variability in ASD presentations. Additional studies are needed before drawing valid recommendations in relation to the cultural sensitivity of particular items.

Genome wide study of tardive dyskinesia in schizophrenia.

Tardive dyskinesia (TD) is a severe condition characterized by repetitive involuntary movement of orofacial regions and extremities. Patients treated with antipsychotics typically present with TD symptomatology. Here, we conducted the largest GWAS of TD to date, by meta-analyzing samples of East-Asian, European, and African American ancestry, followed by analyses of biological pathways and polygenic risk with related phenotypes. We identified a novel locus and three suggestive loci, implicating immune-related pathways. Through integrating trans-ethnic fine mapping, we identified putative credible causal variants for three of the loci. Post-hoc analysis revealed that SNPs harbored in TNFRSF1B and CALCOCO1 independently conferred three-fold increase in TD risk, beyond clinical risk factors like Age of onset and Duration of illness to schizophrenia. Further work is necessary to replicate loci that are reported in the study and evaluate the polygenic architecture underlying TD.

Revisiting Schizophrenia from an Evolutionary Perspective: An Association Study of Recent Evolutionary Markers and Schizophrenia.

The persistence of schizophrenia in human populations at a high prevalence and with a large heritability estimate despite reduced fertility and increased mortality rate is a Darwinian paradox. This may be likely if the genomic components that predispose to schizophrenia are also advantageous for the acquisition of important human traits, such as language and cognition. Accordingly, an emerging group of genomic markers of recent evolution in humans, namely human accelerated regions (HARs), since our divergence from chimpanzees, are gaining importance for neurodevelopmental disorders, such as schizophrenia. We hypothesize that variants within HARs may affect the expression of genes under their control, thus contributing to disease etiology. A total of 49 HAR single nucleotide polymorphisms (SNPs) were prioritized from the complete repertoire of HARs (n = 2737) based on their functional relevance and prevalence in the South Asian population. Test of association using 2 independent schizophrenia case-control cohorts of north Indian ethnicity (discovery: n = 930; replication: n = 1104) revealed 3 SNPs (rs3800926, rs3801844, and rs764453) from chromosome 7 and rs77047799 from chromosome 3 to be significantly associated (combined analysis: Bonferroni corrected P < .002-.000004). Of note, these SNPs were found to alter the expression of neurodevelopmental genes such as SLC25A13, MAD1L1, and ULK4; a few from the HOX gene family; and a few genes that are implicated in mitochondrial function. These SNPs may most likely alter binding sites of transcription factors, including TFCP2, MAFK, SREBF2, E2F1, and/or methylation signatures around these genes. These findings reiterate a neurodevelopmental basis of schizophrenia and also open up a promising avenue to investigate HAR-mediated mitochondrial dysfunction in schizophrenia etiology.

A pilot study on effect of adjunctive transcranial direct current stimulation on symptom domains of depression in patients with depressive disorder.

BACKGROUND: Depression is a highly prevalent condition and includes clusters of symptoms, namely, depressive cognition, anxiety, and visceral symptoms. Depressive symptoms often respond sub-optimally to pharmacotherapy. Adjunctive transcranial direct current stimulation (tDCS), a noninvasive brain stimulation modality, may improve depressive symptomatology. AIM: The aim of this study was to study the effect of tDCS as an augmentation strategy in depression and its various symptom domains. MATERIALS AND METHODS: It is a prospective interventional study. Patients diagnosed with depressive disorder (based on International Classification of Disease- 10 criteria, diagnosed by treating psychiatrist), aged 18-70 years, who showed inadequate improvement on antidepressant selective serotonin reuptake inhibitors, were recruited after informed consent. Each participant was administered 20 sessions of tDCS over 2 weeks, each session of 20 min, with anode placement at left dorsolateral prefrontal cortex and cathode at right supraorbital region. Hamilton Rating Scale for Depression (HAM-D) was administered pre- and post-intervention to assess the change in symptoms. RESULTS: Of a total of 35 participants, the mean score on HAM-D prior to and postintervention was 19.97 (standard deviation [SD] = 3.519) and 13.17 (SD = 3.365), respectively. The difference was statistically highly significant (P = 0.000) on paired t-test. All symptom domains of HAM-D, identified using the Cole and Motivala model (Cole et al., 2004), also showed significant reduction from pre-tDCS to post-tDCS scores (P = 0.000). CONCLUSION: Positive effect of tDCS on depressive symptoms, its tolerability and safety profile, and affordability makes it an effective therapeutic strategy in augmenting antidepressants in patients with depression. However, longer period studies with larger sample size may yield more generalizable results.