Schizophrenia Interactome-Derived Repurposable Drugs and Randomized Controlled Trials of Two Candidates.

There is a substantial unmet need for effective and patient-acceptable drugs to treat severe mental illnesses such as schizophrenia (SZ). Computational analysis of genomic, transcriptomic, and pharmacologic data generated in the past 2 decades enables repurposing of drugs or compounds with acceptable safety profiles, namely those that are U.S. Food and Drug Administration approved or have reached late stages in clinical trials. We developed a rational approach to achieve this computationally for SZ 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 whereby their target networks were enriched for pathways relevant to SZ etiology or for genes that had an association with diseases pathogenically similar to SZ. To translate these computational results to the clinic, these shortlisted drugs must be tested empirically through randomized controlled trials, in which their previous safety approvals obviate the need for time-consuming phase 1 and 2 studies. We selected 2 among the shortlisted candidates based on likely adherence and side-effect profiles. We are testing them through adjunctive randomized controlled trials for patients with SZ 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 the future and should also be exploited for other psychiatric disorders.

Feasibility and acceptability of the Indian Autism Screening Questionnaire in clinical and community settings.

We developed and tested the Indian Autism Screening Questionnaire (IASQ), which was reported to be reliable and valid as compared to the Indian Scale for Assessment of Autism (ISAA) and the Childhood Autism Rating Scale -2 (CARS2). The present study describes the feasibility, acceptability, sociodemographic and developmental details of IASQ study participants in 5 settings- a psychiatry outpatients' clinic (n = 145), a specialised paediatric clinic (n = 24), a speciality disability centre (n = 174), a primary school (n = 41) and a government housing colony (n = 255). The IASQ could be easily administered and understood. Consistent with prior reports, the male-female ratio of participants with autism was 3.8:1. Developmental complications were reported more frequently in clinical settings, while delivery by Caesarean section was commoner among community-dwelling higher socioeconomic status mothers (53% of the officers' sample). Mothers of participants with autism more frequently reported Caesarean section birth for the proband (χ2 = 41.61, p < .0001) and prenatal and postnatal complications. Binary logistic regression confirmed that perinatal complications in the mother and father's (older) age at birth of the participant were associated with autism. The IASQ is a reliable, practical tool for screening for autism in clinical and non-clinical settings in India.

Community practices as coping mechanisms for mental health in Kashmir.

With a steady rise in mental health issues such as depression, anxiety, and post-traumatic stress disorder (PTSD) in Kashmir, the need to address mental health in this region becomes important. This paper reports on traditional and current community mental health coping mechanisms among residents in Kashmir. Six focus group discussions (FGD) were facilitated with key informants. Data were analyzed via a thematic analytic approach. Community coping mechanisms reported include social spaces and shared chore spaces, cultural practices, shrines and religious places, faithealers. These findings demonstrate community strengths that can leverage to build additional coping strategies and resilience among people.

Effect of rs1108580 of DBH and rs1006737 of CACNA1C on Cognition and Tardive Dyskinesia in a North Indian Schizophrenia Cohort.

Genetic perturbations in dopamine neurotransmission and calcium signaling pathways are implicated in the etiology of schizophrenia. We aimed to test the association of a functional splice variant each in Dopamine ß-Hydroxylase (DBH; rs1108580) and Calcium voltage-gated channel subunit alpha1 C (CACNA1C; rs1006737) genes in these pathways with schizophrenia (506 cases, 443 controls); Abnormal Involuntary Movement Scale (AIMS) scores in subjects assessed for tardive dyskinesia (76 TD-positive, 95 TD-negative) and Penn Computerized Neurocognitive Battery (PennCNB) scores (334 cases, 234 controls). The effect of smoking status and SNP genotypes on AIMS scores were assessed using ANOVA; health status and SNP genotypes on three performance functions of PennCNB cognitive domains were assessed by ANCOVA with age and sex as covariates. Association with Positive and Negative Syndrome Scale (PANSS) scores in the TD cohort and cognitive scores in healthy controls of the cognition cohort were tested by linear regression. None of the markers were associated with schizophrenia. Smoking status [F(2, 139) = 10.6; p = 5 × 10-5], rs1006737 [F(2, 139) = 7.1; p = 0.001], TD status*smoking [F(2, 139) = 8.0; p = 5.0 × 10-4] and smoking status*rs1006737 [F(4, 139) = 2.7; p = 0.03] had an effect on AIMS score. Furthermore, rs1006737 was associated with orofacial [F(2, 139) = 4.6; p = 0.01] and limb-truncal TD [(F(2, 139) = 3.8; p = 0.02]. Main effect of rs1108580 on working memoryprocessing speed [F(2, 544) = 3.8; p = 0.03] and rs1006737 on spatial abilityefficiency [F(1, 550) = 9.4; p = 0.02] was identified. Health status*rs1006737 interaction had an effect on spatial memoryprocessing speed [F(1, 550) = 6.9; p = 0.01]. Allelic/genotypic association (p = 0.01/0.03) of rs1006737 with disorganized/concrete factor and allelic association of rs1108580 (p = 0.04) with a depressive factor of PANSS was observed in the TD-negative subcohort. Allelic association of rs1006737 with sensorimotor dexterityaccuracy (p = 0.03), attentionefficiency (p = 0.05), and spatial abilityefficiency (p = 0.02); allelic association of rs1108580 with face memoryaccuracy (p = 0.05) and emotionefficiency (p = 0.05); and allelic/genotypic association with emotionaccuracy (p = 0.003/0.009) were observed in healthy controls of the cognition cohort. These association findings may have direct implications for personalized medicine and cognitive remediation.

An open-label study of oral acetazolamide for the prevention of antipsychotic associated weight gain.

Background: Weight gain associated with atypical antipsychotic medications need to be well managed. We set out: 1. To test the effect of acetazolamide on weight gain associated with antipsychotics 2. To assess improvement in psychotic symptoms using the Brief Psychiatric Rating Scale score on patients receiving acetazolamide. Methods and Materials: This open-label study conducted after institutional ethical clearance from December 2018 to August 2020 included 34 drug-naive patients or patients on antipsychotic risperidone or olanzapine for less than one month. They were divided into two groups of 17 each as a case group (treatment as usual + acetazolamide) and a control group (treatment as usual) who were followed up for eight weeks. The patient's physical characteristics were recorded at baseline and during follow-ups. The Brief psychiatric rating scale (BPRS) and clinical global impression (CGI) scores were compared for the cases and controls. Results: The study showed non-significant reduction in the weight (-0.57 ± 1.06 kg), body mass index (BMI) (-0.23 ± 0.76 kg/m2) and abdominal circumference (-0.47 ± 1.37 cm) in the patients receiving oral acetazolamide at the end of two months as compared to controls where there was significant increase in the weight (+2.62 ± 1.09 kg), BMI (+1.03 ± 0.44 kg/m2) and abdominal circumference (+2.21 ± 1.33 cm, P = 0.001). Similarly, the BPRS and CGI scores were significantly reduced in both arms, with satisfaction rates better among the cases compared to controls. Conclusion: There was a non-significant reduction in the weight, body mass index, abdominal circumference, and brief psychiatric rating scale scores in patients treated with acetazolamide.Ethics committee protocol number: - 2018/244CTRI India registration number: CTRI/2019/05/018884.

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.

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.

An Assessment of the Training Program on Mental Health for Community Health Workers in Kashmir, India.

In recent years mental health has emerged as a major health threat in low income countries like India. In response, mental health care has been integrated into primary health care, in turn creating a rising demand for trained and skillful mental health professionals. This study was conducted in district Budgam (J&K), India with the aim of providing training to community health workers (CHWs) and measuring the change using pre- and post-training evaluations. The pre and post tests were undertaken, assessing changes in mental health literacy at three different points of time: pre-training, post-training, and three month follow-up. Mental health literacy was assessed using the interviewer-administered Mental Health Literacy Survey. The training intervention was a five-day course based on a facilitator's manual developed specifically for community health workers in India. A total of 25 community health workers from rural areas of Budgam District (mostly Integrated Child Development Service supervisors), Health Educators and Anganwadi Workers, were engaged for the study. Findings demonstrate that the training course improved participants' ability to recognize any mental health disorders. There was a clear distinction between the level of awareness pre- and post- training. The results were statistically significant on various domains Ability to recognize disorders (Pre-post P= 0.001), Knowledge of the professional help available (Pre-post p= 0.000), Attitudes that promote the recognition or appropriate help-seeking behavior (Pre-post p= 0.000) (p<0.05). Further follow up after three months was done. The mixed findings from this study, suggesting the training course has potential to improve some aspects of mental health literacy among the CHWs, including their understanding of various mental health problems.

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.

Comparing the Indian Autism Screening Questionnaire (IASQ) and the Indian Scale for Assessment of Autism (ISAA) with the Childhood Autism Rating Scale-Second Edition (CARS2) in Indian settings.

The Indian Autism Screening Questionnaire (IASQ), derived from the Indian Scale for Assessment of Autism ISAA (the mandated tool for autism in India), is an autism screening instrument for use in the general population by minimally trained workers. While ISAA has 40 items with four anchor points, the IASQ is a 10-item questionnaire with yes/no answers. It was initially validated using the ISAA. During its development the ISAA was itself compared to the Childhood Autism Rating Scale version 1 (ISAA Manual). In the present study, we evaluated both the ISAA and the IASQ in relation to the Childhood Autism Rating Scale version 2 (CARS-2). METHODS: Participants were recruited from three settings: a referral clinic for neurodevelopmental conditions run by the Department of Paediatrics of a tertiary care teaching hospital (NDC OPD), the outpatient department of an institute for disability and rehabilitation (NIEPID), and from the community (CGOC). Persons between ages 3-18 were recruited following consent or assent (parent and child/adolescent). The IASQ was administered by a minimally trained administrator. It was followed by ISAA and the CARS-2 (in alternating order, by different evaluators blind to each other) (CARS2 SV (Standard Version) and CARS2 HF (High Functioning) as applicable). Sensitivity, specificity and area under the Receiver Operator Characteristics (ROC) curve were calculated for IASQ and CARS2, as well as for ISAA and CARS2. Concordance between CARS2 and ISAA was calculated using kappa coefficient. RESULTS: A total of 285 participants (NIEPD n = 124; NDC OPD, n = 4; CGOC n = 157) (a total of 70 with autism and 215 controls) participated. IASQ and CARS2 were administered on 285 participants, while IASQ and ISAA were administered on 264 participants. When IASQ was compared to CARS2, sensitivity was 97%, specificity 81%, PPV 63%, NPV 99% at cut off 1 while these values were 97%, 92%, 79% and 99% respectively at cut off 2. There was high concordance between CARS2 and ISAA (Kappa 0.907, p<0.0001). CONCLUSIONS: IASQ has satisfactory sensitivity, specificity and concordance when compared with CARS2; it can be used for screening children with autism in community. The ISAA also showed a high concordance with CARS2, as it had with the older version of CARS.

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.

Assessment of Anxiety and Depression among Adult Population of Kashmir, India: A Cross-sectional Study.

Introduction: Mental health in Kashmir remains a concern and is threatening to become an ever-increasing epidemic. The changing social structure and the low-intensity armed conflict have become the basis of a deteriorating state of mental health among Kashmiris. In addition to this, the other factors are widespread poverty, uncertainty, grief, oppression, fear and high unemployment with limited employment generating sectors. Aim: To assess the depression, anxiety and mental distress among the adult population of Budgam district, Kashmir, India. Materials and Methods: A cross-sectional study was conducted at the community level in District Budgam, Jammu and Kashmir, India, from December 2019 to March 2020. Total three Investigators, one Senior Research Fellow (SRF) and two Junior Research Fellow (JRF) collected the data. The SRF was a Clinical Psychologist while the JRF were trained social workers. A door to door survey was conducted in the villages which were selected randomly from the list of the villages. The probability random sampling technique was used for the research purpose. Hopkins Symptoms Checklist-25 (HSCL-25) was used in the study and whereby after analysing the scores of the scale, results were derived. Chi-square and t-test were applied for statistical comparison. Results: Out of 133 individuals, 55 were males and 78 were females.The age of the sample ranged from 18 to 45 years, with a mean age of 37 years. Total 29.32% of the adults scored above the cut-off for anxiety symptoms and 34.58% scored above the cut-off for depressive symptoms, while 39% of these adults fall above the cut-off for mental distress scores.The validated cut-off score for the anxiety was 1.75 and for the depression was 1.57. Feeling tense, being worried, nervousness and low energy were reported as the symptoms of the mental distress among the people. Females, unemployed and individuals from lower socio-economic status reported higher degree of mental distress than others. Conclusion: Mental health issues in terms of anxiety, depression, and mental distress are found among the adult population in district Budgam. There was a significant mean difference in the mental distress levels concerning various socio-demographic variables. The study concluded that being female, having some medical condition, being unemployed, belonging to lower socio-economic status, belonging to nuclear family predict mental health distress.

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.

Psychometric properties of a screening tool for autism in the community-The Indian Autism Screening Questionnaire (IASQ).

INTRODUCTION: Currently available screening questionnaires for Autism spectrum disorders were tested in developed countries, but many require additional training and many are unsuitable for older individuals, thus reducing their utility in lower/ middle- income countries. We aimed to derive a simplified questionnaire that could be used to screen persons in India. METHODS: We have previously validated Indian Scale for Assessment of Autism (ISAA), that is now mandated for disability assessment by the Government of India. This detailed tool requires intensive training and it is time consuming. It was used to derive a new screening questionnaire: 1) items most frequently scored as positive by participants with autism in original ISAA validation study were modified for binary scoring following expert review. 2) In a new sample, clinically diagnosed individuals with/without autism were administered the screening tool and ISAA following written informed consent. Its psychometric properties were determined. RESULTS: A 10-item scale named Indian Autism Screening Questionnaire (IASQ) was prepared in Hindi and English. Thereafter 145 parents/caregivers of participants (autism, n = 90, other psychiatric disorders, n = 55) (ages 3-18), were administered IASQ and ISAA (parents/caregivers plus observation) by separate interviewers, blind to each other and to diagnosis. At a cutoff of 1, sensitivity was 99%, specificity 62%, Positive Predictive Value 81%, and Negative Predictive Value 95%. Test-retest reliability was r = 0.767 (CI = 0.62-0.86) and interrater reliability- Krippendorff"s-alpha was 0.872. The area under Receiver Operating Characteristic Curve (ROC) was 95%. There was a significant difference on IASQ-scores between participants with and without a clinical diagnosis of Autism (t = 14.57, p<0.0001). DISCUSSION: The IASQ is a simple, easy to use screening tool with satisfactory reliability and validity, that can be administered to caregivers in 15 minutes and provides information about DSM 5 criteria for autism. It may be applicable outside India, following additional adaptation, for community-based studies.

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.