Background Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. Methods Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. Results 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5–11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4–31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1–3.5). Conclusion ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and ‘trauma-informed’ approaches to tackling longer-term impact of ACEs in India. Funding Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

BackgroundLow and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders.MethodscVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively.DiscussionThe cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

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Alcohol use disorder (AUD) is a chronic and fatal disease. The main impediment of the AUD therapy is a high probability of relapse to alcohol abuse even after prolonged abstinence. The molecular mechanisms of cue-induced relapse are not well established, despite the fact that they may offer new targets for the treatment of AUD. Using a comprehensive animal model of AUD, virally-mediated and amygdala-targeted genetic manipulations by CRISPR/Cas9 technology and ex vivo electrophysiology, we identify a mechanism that selectively controls cue-induced alcohol relapse and AUD symptom severity. This mechanism is based on activity-regulated cytoskeleton-associated protein (Arc)/ARG3.1-dependent plasticity of the amygdala synapses. In humans, we identi ed single nucleotide polymorphisms in the ARC gene and their methylation predicting not only amygdala size, but also frequency of alcohol use, even at the onset of regular consumption. Targeting Arc during alcohol cue exposure may thus be a selective new mechanism for relapse prevention.

Anatomical brain templates are commonly used as references in neurological MRI studies, for bringing data into a common space for group-level statistics and coordinate reporting. Given the inherent variability in brain morphology across age and geography, it is important to have templates that are as representative as possible for both age and population. A representative-template increases the accuracy of alignment, decreases distortions as well as potential biases in final coordinate reports. In this study, we developed and validated a new set of T1w Indian brain templates (IBT) from a large number of brain scans (total n = 466) acquired across different locations and multiple 3T MRI scanners in India. A new tool in AFNI, make_template_dask.py, was created to efficiently make five age-specific IBTs (ages 6-60 years) as well as maximum probability map (MPM) atlases for each template; for each age-group's template-atlas pair, there is both a "population-average" and a "typical" version. Validation experiments on an independent Indian structural and functional-MRI Bharath Holla and Paul A. Taylor are the equally contributing authors.

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Human brain morphology undergoes complex developmental changes with diverse regional trajectories. Various biological factors influence cortical thickness development, but human data are scarce. Building on methodological advances in neuroimaging of large cohorts, we show that population-based developmental trajectories of cortical thickness unfold along patterns of molecular and cellular brain organization. During childhood and adolescence, distributions of dopaminergic receptors, inhibitory neurons, glial cell populations as well as features of brain metabolism explain up to 50% of variance associated with regional cortical thickness trajectories. Cortical maturation patterns in later life are best explained by distributions of cholinergic and glutamatergic systems. These observations are validated in longitudinal data from over 8,000 adolescents, explaining up to 59% of developmental change at population- and 18% at single-subject level. Integrating multilevel brain atlases with normative modeling and population neuroimaging provides a biologically and clinically meaningful path to understand typical and atypical brain development in living humans.

IntroductionIndia is home to 20% of the world’s children and yet, little is known on the magnitude and trends of child maltreatment nationwide. The aims of this review are to provide a prevalence of child maltreatment in India with considerations for any effects of gender; urbanisation (eg, urban vs rural) and legislation (Protection of Children from Sexual Offences (POCSO) Act 2012).Methods and analysisA rapid review will be undertaken of all quantitative peer-reviewed studies on child maltreatment in India between 2005 and 2020. Four electronic databases will be systematically searched: PubMed, EMBASE, Cochrane and PsychInfo. The primary outcomes will include all aspects of child maltreatment: physical abuse, sexual abuse, emotional abuse, emotional neglect and physical neglect. Study participants will be between 0 and 18 years and will have reported maltreatment experiences using validated, reliable tools such as the Adverse Childhood Experiences Questionnaire as well as child self-reports and clinician reports. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the methodological appraisal of the studies will be assessed by the Newcastle-Ottawa Quality assessment scale. A narrative synthesis will be conducted for all included studies. Also, if sufficient data are available, a meta-analysis will be conducted. Effect sizes will be determined from random-effects models stratified by gender, urbanisation and the pre-2012 and post-2012 POCSO Act cut-off. I2 statistics will be used to assess heterogeneity and identify their potential sources and τ2 statistics will indicate any between-study variance.Ethics and disseminationAs this is a rapid review, minimal ethical risks are expected. The protocol and level 1 self-audit checklist were submitted and approved by the Usher Research Ethics Group panel in the Usher Institute (School of Medicine and Veterinary Sciences) at the University of Edinburgh (Reference B126255). Findings from this review will be disseminated widely through peer-reviewed publications and in various media, for example, conferences, congresses or symposia.PROSPERO registration numberCRD42019150403.