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.

A mentored hands-on training model for scaling up implementation and intervention research in India: "connecting the dots".

Despite the high burden of mental disorders in low- and middle-income countries (LMICs), less than 25% of those in need have access to appropriate services, in part due to a scarcity of locally relevant, evidence-based interventions and models of care. To address this gap, researchers from India and the United States and the Indian Council of Medical Research (ICMR) collaboratively developed a "Grantathon" model to provide mentored research training to 24 new principal investigators (PIs). This included a week-long didactic training, a customized web-based data entry/analysis system and a National Coordination Unit (NCU) to support PIs and track process objectives. Outcome objectives were assessed via scholarly output including publications, awards received and subsequent grants that were leveraged. Multiple mentorship strategies including collaborative problem-solving approaches were used to foster single-centre and multicentre research. Flexible, approachable and engaged support from mentors helped PIs overcome research barriers, and the NCU addressed local policy and day-to-day challenges through informal monthly review meetings. Bi-annual formal review presentations by all PIs continued through the COVID-19 pandemic, enabling interim results reporting and scientific review, also serving to reinforce accountability. To date, more than 33 publications, 47 scientific presentations, 12 awards, two measurement tools, five intervention manuals and eight research grants have been generated in an open-access environment. The Grantathon is a successful model for building research capacity and improving mental health research in India that could be adopted for use in other LMICs.

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.

Adjunctive yoga training for persons with schizophrenia: who benefits?

OBJECTIVE: The aim of this study was to identify factors associated with acceptability and efficacy of yoga training (YT) for improving cognitive dysfunction in individuals with schizophrenia (SZ). METHODS: We analysed data from two published clinical trials of YT for cognitive dysfunction among Indians with SZ: (1) a 21-day randomised controlled trial (RCT, N = 286), 3 and 6 months follow-up and (2) a 21-day open trial (n = 62). Multivariate analyses were conducted to examine the association of baseline characteristics (age, sex, socio-economic status, educational status, duration, and severity of illness) with improvement in cognition (i.e. attention and face memory) following YT. Factors associated with acceptability were identified by comparing baseline demographic variables between screened and enrolled participants as well as completers versus non-completers. RESULTS: Enrolled participants were younger than screened persons who declined participation (t = 2.952, p = 0.003). No other characteristics were associated with study enrollment or completion. Regarding efficacy, schooling duration was nominally associated with greater and sustained cognitive improvement on a measure of facial memory. No other baseline characteristics were associated with efficacy of YT in the open trial, the RCT, or the combined samples (n = 148). CONCLUSIONS: YT is acceptable even among younger individuals with SZ. It also enhances specific cognitive functions, regardless of individual differences in selected psychosocial characteristics. Thus, yoga could be incorporated as adjunctive therapy for patients with SZ. Importantly, our results suggest cognitive dysfunction is remediable in persons with SZ across the age spectrum.

Informed consent in psychiatry outpatients.

Background & objectives: Comprehension and process of consent are important for persons with mental illness as they may not be impaired in considering research participation. The American Psychiatric Association developed a detailed Cultural Formulation Interview (CFI). The present study was a part of field testing of CFI, aimed to standardize cultural information affecting the patients' management in India. This paper describes the process and conclusions from the consent-seeking process of this study. Methods: The purpose and procedures about field trial of the CFI were introduced and the patient and caregiver were requested for participation. Consent process was carried out step by step, by reading out the consent form to the first new patient of the day in the psychiatry outpatients department of a tertiary care hospital in north India, inviting questions followed by the 'comprehension' questions. The entire process was audiotaped without any personal identifiers. The process was repeated if not comprehended. Results: A total of 67 patients consented, 11 refused and majority were educated more than secondary school. Some concerns shown by the patients and caregivers included risk of participation, loss or benefits of participation, privacy, etc. All types of mentally ill patients participated in the study. Interpretation & conclusions: Translations of consent forms used simple words, consonant with understanding of the potential participants. Patients' belief that participating in this long process would improve their care, and serve humanity, influenced their decision to participate. Except for intoxication and severe psychosis, patients could understand and comprehend issues around consent. Main issues were confidentiality and culture. Our experience in the psychiatry OPD refutes the commonly held belief that mentally ill persons lack comprehension and ability to consent.

Outcomes from Indo-United States-Egypt tri-national psychiatric research training programmes.

BACKGROUND: The prevalence of mental health disorders is increasing globally. Countries in South Asia, Southeast Asia and the Middle East regions carry high burdens of mental health need; however, there are relatively few mental health research publications from this region, suggesting inadequate research funds and a paucity of qualified research personnel. To increase and strengthen the pool of mental health researchers in India and Egypt, we conducted three psychiatric research programmes in these countries: the Training Program for Psychiatric Genetics in India (2002-2011), the Tri-National Training Program for Psychiatric Genetics (2009-2014) and the Cross-Fertilized Research Training for New Investigators in Egypt and India (2014-2019). A total of 66 trainees, including psychiatrists, psychiatric social workers, clinical psychologists and research psychologists, were supported in research development, which included didactic training, proposal development, hands-on research and manuscript preparation. METHODS: The aim of this study is to evaluate these three training programmes using the four-level Kirkpatrick Model of Training Evaluation that assesses reaction, learning, behaviour and outcomes. A descriptive analysis was used to explore the data collected throughout the duration of the three training programmes. Online surveys were crafted and sent to the mentors and trainees of the three programmes to supplement objective training data. RESULTS: In addition to positive changes in the areas of reaction, learning and behaviour, significant outcomes were demonstrated. As of the writing of this manuscript, the trainees published a total of 130 papers, 59 as first author. In addition, 26 trainees have co-authored papers with one or more trainees or mentors, which demonstrates successful research networking and collaboration. CONCLUSION: Our findings suggest that our training approach is a successful model for building independent mental health researchers. This is a critical step in the development of effective mental health interventions in low- and middle-income countries.

Determination of Dopamine-ß-hydroxylase Activity in Human Serum Using UHPLC-PDA Detection.

Dopamine-ß-hydroxylase (DBH, EC 1.14.17.1) is an enzyme with implications in various neuropsychiatric and cardiovascular diseases and is a known drug target. There is a dearth of cost effective and fast method for estimation of activity of this enzyme. A sensitive UHPLC based method for the estimation of DBH activity in human sera samples based on separation of substrate tyramine from the product octopamine in 3 min is described here. In this newly developed protocol, a Solid Phase Extraction (SPE) sample purification step prior to LC separation, selectively removes interferences from the reaction cocktail with almost no additional burden on analyte recovery. The response was found to be linear with an r2 = 0.999. The coefficient of variation for assay precision was < 10% and recovery > 90%. As a proof of concept, DBH activity in sera from healthy human volunteers (n = 60) and schizophrenia subjects (n = 60) were successfully determined using this method. There was a significant decrease in sera DBH activity in subjects affected by schizophrenia (p < 0.05) as compared to healthy volunteers. This novel assay employing SPE to separate octopamine and tyramine from the cocktail matrix may have implications for categorising subjects into various risk groups for Schizophrenia, Parkinson's disease as well as in high throughput screening of inhibitors.

Evidence for regional hippocampal damage in patients with schizophrenia.

PURPOSE: Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy (1H MRS) procedures. METHODS: 1H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). RESULTS: Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. CONCLUSION: Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients.

Feasibility, acceptability and clinical utility of the Cultural Formulation Interview: mixed-methods results from the DSM-5 international field trial.

BackgroundThere is a need for clinical tools to identify cultural issues in diagnostic assessment.AimsTo assess the feasibility, acceptability and clinical utility of the DSM-5 Cultural Formulation Interview (CFI) in routine clinical practice.MethodMixed-methods evaluation of field trial data from six countries. The CFI was administered to diagnostically diverse psychiatric out-patients during a diagnostic interview. In post-evaluation sessions, patients and clinicians completed debriefing qualitative interviews and Likert-scale questionnaires. The duration of CFI administration and the full diagnostic session were monitored.ResultsMixed-methods data from 318 patients and 75 clinicians found the CFI feasible, acceptable and useful. Clinician feasibility ratings were significantly lower than patient ratings and other clinician-assessed outcomes. After administering one CFI, however, clinician feasibility ratings improved significantly and subsequent interviews required less time.ConclusionsThe CFI was included in DSM-5 as a feasible, acceptable and useful cultural assessment tool.

A 'Grantathon' model to mentor new investigators in mental health research.

BACKGROUND: There is a critical gap between needs and available resources for mental health treatment across the world, particularly in low- and middle-income countries (LMICs). In countries committed to increasing resources to address these needs it is important to conduct research, not only to assess the depth of mental health needs and the current provision of public and private mental health services, but also to examine implementation methods and evaluate mental health approaches to determine which methods are most effective in local contexts. However, research resources in many LMICs are inadequate, largely because conventional research training is time-consuming and expensive. Adapting a hackathon model may be a feasible method of increasing capacity for mental health services research in resource-poor countries. METHODS: To explore the feasibility of this approach, we developed a 'grantathon', i.e. a research training workshop, to build capacity among new investigators on implementation research of Indian government-funded mental health programmes, which was based on a need expressed by government agencies. The workshop was conducted in Delhi, India, and brought together junior faculty members working in mental health services settings throughout the country, experienced international behavioural health researchers and representatives of the Indian Council for Medical Research (ICMR), the prime Indian medical research funding agency. Pre- and post-assessments were used to capture changes in participants' perceived abilities to develop proposals, design research studies, evaluate outcomes and develop collaborations with ICMR and other researchers. Process measures were used to track the number of single-or multi-site proposals that were generated and funded. RESULTS: Participants (n = 24) generated 12 single- or multi-site research grant applications that will be funded by ICMR. CONCLUSION: The grantathon model described herein can be modified to build mental health services research capacity in other contexts. Given that this workshop not only was conceptualised and delivered but also returned results in less than 1 year, this model has the potential to quickly build research capacity and ultimately reduce the mental health treatment gap in resource-limited settings.

A randomised controlled trial of adjunctive yoga and adjunctive physical exercise training for cognitive dysfunction in schizophrenia.

BACKGROUND: Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking. Aims A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study. METHODS: Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of 'attention' in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm. RESULTS: Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (p<0.036, effect size 0.51). In the PE group, 'accuracy index of attention domain showed greater improvement than TAU alone at 6-month follow-up (p<0.025, effect size 0.61). For several other cognitive domains, significant improvements were observed with YT or PE compared with TAU alone (p<0.05, effect sizes 0.30-1.97). CONCLUSIONS: Both YT and PE improved attention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.

Deep sequencing identifies novel regulatory variants in the distal promoter region of the dopamine-ß-hydroxylase gene.

OBJECTIVE: Dopamine-ß-hydroxylase (DBH), an enzyme that converts dopamine into norepinephrine, is a drug target in cardiovascular and neuropsychiatric disorders. We aimed to identify functional variants in this gene by deep sequencing and enzyme phenotyping in an Indian cohort. MATERIALS AND METHODS: Targeted resequencing of 12 exons and 10 kb upstream sequences of DBH in healthy volunteers (n=50) was performed using the Ion Personal Genome Machine System. Enzyme quantity and activity in their sera samples were determined by ELISA and ultra performance liquid chromatography, respectively. The association of markers with phenotypes was determined using Matrix eQTL. Global P-values for haplotypes generated using UNPHASED 3.1.5 were graphed using GrASP v.082 beta. RESULTS: Of the 49 variants identified, nine were novel (minor allele frequency≥0.01). Though individual markers associated with enzyme quantity did not withstand multiple corrections, a novel distal promoter block driven by rs113249250 (global P=1.5×10) was associated. Of the nine single nucleotide polymorphisms (SNPs) associated with enzyme activity, rs3025369, rs1076151 and rs1611115, all from the upstream region, withstood false discovery rate correction (false discovery rate=0.03, 0.03 and 2.9×10, respectively). Conditioning for rs1611115 identified rs1989787 also to affect activity. Importantly, we report an association of a novel haplotype block distal to rs1076151 driven by rs3025369 (global P=8.9×10) with enzyme activity. This regulatory SNP explained 4.9% of the total 46.1% of variance in DBH activity caused by associated SNPs. CONCLUSION: This first study combining deep sequencing and enzyme phenotyping identified yet another regulatory SNP suggesting that regulatory variants may be central in the physiological or metabolic role of this gene of therapeutic and pharmacological relevance.

How Do Clinicians Prefer Cultural Competence Training? Findings from the DSM-5 Cultural Formulation Interview Field Trial.

OBJECTIVE: This study's objective is to analyze training methods clinicians reported as most and least helpful during the DSM-5 Cultural Formulation Interview field trial, reasons why, and associations between demographic characteristics and method preferences. METHOD: The authors used mixed methods to analyze interviews from 75 clinicians in five continents on their training preferences after a standardized training session and clinicians' first administration of the Cultural Formulation Interview. Content analysis identified most and least helpful educational methods by reason. Bivariate and logistic regression analysis compared clinician characteristics to method preferences. RESULTS: Most frequently, clinicians named case-based behavioral simulations as "most helpful" and video as "least helpful" training methods. Bivariate and logistic regression models, first unadjusted and then clustered by country, found that each additional year of a clinician's age was associated with a preference for behavioral simulations: OR = 1.05 (95 % CI: 1.01-1.10; p = 0.025). CONCLUSIONS: Most clinicians preferred active behavioral simulations in cultural competence training, and this effect was most pronounced among older clinicians. Effective training may be best accomplished through a combination of reviewing written guidelines, video demonstration, and behavioral simulations. Future work can examine the impact of clinician training satisfaction on patient symptoms and quality of life.

Perspectives of family members participating in cultural assessment of psychiatric disorders: findings from the DSM-5 International Field Trial.

Despite the important roles families play in the lives of many individuals with mental illness across cultures, there is a dearth of data worldwide on how family members perceive the process of cultural assessment as well as to how to best include them. This study addresses this gap in our knowledge through analysis of data collected across six countries as part of a DSM-5 Field Trial of the Cultural Formulation Interview (CFI). At clinician discretion, individuals who accompanied patients to the clinic visit (i.e. patient companions) at the time the CFI was conducted were invited to participate in the cultural assessment and answer questions about their experience. The specific aims of this paper are (1) to describe patterns of participation of patient companions in the CFI across the six countries, and (2) to examine the comparative feasibility, acceptability, and clinical utility of the CFI from companion perspectives through analysis of both quantitative and qualitative data. Among the 321 patient interviews, only 86 (at four of 12 sites) included companions, all of whom were family members or other relatives. The utility, feasibility and acceptability of the CFI were rated favourably by relatives, supported by qualitative analyses of debriefing interviews. Cross-site differences in frequency of accompaniment merit further study.

Motor function deficits in schizophrenia: an fMRI and VBM study.

INTRODUCTION: To investigate whether the motor functional alterations in schizophrenia (SZ) are also associated with structural changes in the related brain areas using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). METHODS: A sample of 14 right-handed SZ patients and 14 right-handed healthy control subjects matched for age, sex, and education were examined with structural high-resolution T1-weighted MRI; fMRI images were obtained during right index finger-tapping task in the same session. RESULTS: fMRI results showed reduced functional activation in the motor areas (contralateral precentral and postcentral gyrus) and ipsilateral cerebellum in SZ subjects as compared to healthy controls (n = 14). VBM analysis also revealed reduced grey matter in motor areas and white matter reduction in cerebellum of SZ subjects as compared to controls. CONCLUSION: The present study provides an evidence for a possible association between structural alterations in the motor cortex and disturbed functional activation in the motor areas in persons affected with SZ during a simple finger-tapping task.

A comparative study of fixed tapering dose regimen versus symptom-triggered regimen of lorazepam for alcohol detoxification.

AIMS: The study aimed at comparing the fixed tapering dose and the symptom-triggered regimens of lorazepam for alcohol detoxification. METHODS: We carried out a prospective, randomized, double blind controlled trial involving 63 consecutive consenting male patients admitted with diagnosis of uncomplicated alcohol withdrawal. The patients were randomized into two groups based on the type of lorazepam dosage: symptom-triggered (n = 33) and fixed tapering dose regimens (n = 30). Alcohol withdrawal symptoms were rated on CIWA-Ar (Clinical Institute Withdrawal Assessment - Alcohol revised). The main outcome measures were the total amount and duration of lorazepam treatment and the incidence of adverse events or complications. RESULTS: The mean lorazepam dose administered in the symptom-triggered group was significantly lower than in the fixed tapering dose group (9.5 versus 19.9 mg, P < 0.001) and for a significantly shorter duration of time (47.8 versus 146 h, P < 0.001) with more significant results for higher initial CIWA-Ar scores. There were no significant differences between both the groups in terms of the incidence of complications like seizures or delirium tremens. CONCLUSION: Symptom-triggered lorazepam treatment for alcohol withdrawal resulted in administration of lower total doses of medication for a shorter duration of treatment and was as safe as the fixed tapering dose.

Knowledge & attitudes of mental health professionals regarding psychiatric research.

BACKGROUND & OBJECTIVES: Mental health professionals have varied attitudes and views regarding informed consent and confidentiality protections in psychiatric research and clinical care. The present study was designed to understand the knowledge and views of mental health professionals (MHPs) regarding informed consent and confidentiality protection practices. METHODS: Mental health professionals (n=121) who were members of the Delhi Psychiatric Society, were invited to participate in this questionnaire-based study of their knowledge and attitudes regarding informed consent and confidentiality. Half of them expressed willingness to discuss participation and gave initial oral consent (n=62); of these, 31 gave written informed consent to participate and completed the questionnaires. The questionnaires included both forced choice (yes / no / do not know) and open-ended questions. Questionnaires content reflected prominent guidelines on informed consent and confidentiality protection. RESULTS: Attitudes of the majority of the participants towards informed consent and confidentiality were in line with ethical principles and guidelines. All expressed the opinion that confidentiality should generally be respected and that if confidentiality was breached, there could be mistrust of the professional by the patient/participant. The mean knowledge scores regarding informed consent and confidentiality were 8.55 ± 1.46 and 8.16 ± 1.29, respectively. INTERPRETATION & CONCLUSIONS: The participating mental health professionals appeared to have adequate knowledge of basic ethical guidelines concerning informed consent and confidentiality. Most respondents were aware of ethical issues in research. Given the small sample size and low response rate, the significance of the quantitative analysis must be regarded with modesty, and qualitative analysis of open-ended questions may be more valuable for development of future research. Increased efforts to involve mental health professionals in research on ethical concerns pertinent to their work must be made, and the actual practices of these professionals with regard to ethical guidelines need to be studied.

Protocol to evaluate the impact of yoga supplementation on cognitive function in schizophrenia: a randomised controlled trial.

BACKGROUND: Schizophrenia (SZ) is a chronic illness that is treated symptomatically. Cognitive dysfunction is a core feature of SZ that is relatively intractable to pharmacotherapy. Yoga can improve cognitive function among healthy individuals. A recent open trial indicated significant benefits of yoga training (YT) in conjunction with conventional pharmacotherapy among patients with SZ. AIMS: To describe the protocol for an ongoing randomised controlled trial designed to test whether the reported beneficial effects of YT on cognitive function among SZ patients can be replicated. Secondarily, the effects of YT on daily functioning living skills are evaluated. METHODS: Consenting patients with SZ receive routine clinical treatment and are randomised to adjunctive YT, adjunctive physical exercise (PE) or treatment as usual (proposed N = 234 total, N = 78 in each group). The trial involves YT or PE 5 days a week and lasts 3 weeks. Participants are evaluated thrice over 6 months. Cognitive functions measured by Trail Making Test, University of Pennsylvania Neurocognitive Computerised Battery were primary outcome measures while clinical severity and daily functioning measured by Independent Living Skills Survey were secondary outcome measures. RESULTS: A total of 309 participants have been randomised as of 31 August 2013, which exceeded beyond 294 proposed after attrition. Once participants begin YT or PE they generally complete the protocol. No injuries have been reported. CONCLUSIONS: Short term YT is feasible and acceptable to Indian SZ patients. If beneficial effects of YT are detected, it will provide a novel adjunctive cognitive remediation strategy for SZ patients.

Schizophrenia interactome derived repurposable drugs and randomized control trials of two candidates.

There is a substantial unmet need for effective and patient-acceptable drugs to treat severe mental illnesses like schizophrenia. Computational analysis of genomic, transcriptomic, and pharmacologic data generated in the past two decades enables repurposing of drugs or compounds with acceptable safety profiles, namely those that are FDA-approved or reached late stages in clinical trials. We developed a rational approach to achieve this computationally for schizophrenia by studying drugs that target the proteins in its protein interaction network ('interactome'). This involved contrasting the transcriptomic modulations observed in the disorder and the drug; our analyses resulted in 12 candidate drugs, 9 of which had additional supportive evidence: their target networks were enriched for pathways relevant to schizophrenia etiology or for genes that had an association with diseases pathogenically similar to schizophrenia. To translate these computational results to the clinic, these shortlisted drugs must be tested empirically through randomized controlled trials (RCT), where their prior safety approvals obviate the need for time-consuming phase I and II studies. We selected two among the shortlisted candidates based on likely adherence and side effect profiles. We are testing them through adjunctive RCTs for patients with schizophrenia or schizoaffective disorder who experienced incomplete resolution of psychotic features with conventional treatment. The integrated computational analysis for identifying and ranking drugs for clinical trials can be iterated as additional data are obtained. Our approach could be expanded to enable disease subtype-specific drug discovery in future and should also be exploited for other psychiatric disorders.

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.