Consortium on Vulnerability to Externalizing Disorders and Addictions [c-VEDA]

Alcohol use disorders (AUD) account for a disproportionately high share of the health burden in India and other low- and middle-income countries. This increasing burden is linked to societal changes in emerging nations, which include growing availability of alcohol, greater normalization of use and rapid changes in socio-economic conditions. Individuals with externalising behaviour, which are characterised by altered brain activity during reward processing and behavioural control have a higher risk for AUD. AUD and externalizing disorders share moderate to high heritability with environmental factors being important contributors. While both environmental and genetic factors conveying risk and resilience have been identified it is not established to what extent these factors are dependent on the wider socio-cultural and psychosocial context they are embedded in, or whether they are influenced by epigenetic and genetic factors that are specific for certain ethnicities. It is therefore unknown to what extent environmental and genetic risk factors are similar or distinct in industrialised nations and emerging societies such as in India. Furthermore, some environmental risk factors are largely specific to emerging societies, including exposure to nutritional stress, environmental neurotoxins and culturally dependent forms of psychosocial stress. We propose to investigate in collaboration with Prof. Vivek Benegal of the National Institute for Mental Health and Neurosciences (NIMHANS), Bangalore and our Indian partners from Bangalore, Mysore, Calcutta, Chandigarh and Pune if environmental and genetic risk factors in industrialised countries and emerging societies shape brain function and behaviour in distinct ways, thus leading to different risk constellations and neurobehavioural trajectories for substance misuse and externalising disorders. To address this aim we will establish a comprehensive database allowing comparative analyses of behavioural trajectories in childhood and adolescence, which provide a platform for sustained India-UK collaborations in mental health research. This platform will ascertain a great variety of environmental factors (exposome), biological samples as well as detailed neuroimaging analyses. We propose to compare insights into etiology and trajectories into substance abuse and externalising disorders gained from major European and UK studies including the longitudinal imaging genetics study "Reinforcement-related behaviour in normal development and psychopathology" (IMAGEN) and the "Avon Longitudinal Study of Parents and Children" (ALSPAC) with existing Indian cohorts. The Indian cohorts, which comprise >14.000 participants with aged 0-25 years include both high risk for substance misuse and population-based individuals from different social and environmental (rural and urban) backgrounds. They have been selected to cover the developmental period assessed in the UK cohorts, thus rendering the studies comparable. We aim to enrich the Indian cohorts, which have mainly been designed to investigate somatic disorders by adding a comprehensive assessment of mental health, externalising behaviour and substance use disorders involving psychometric and neuropsychological characterisation, as well as biological sampling in >10.000 participants with an age range of 6-23 years. Assessment instruments and protocols have been selected to allow comparison to IMAGEN and ALSPAC. We will randomly select among the cohort participants 1000 individuals aged between 10 and 23 years for neuroimaging, genetic and epigenetic analyses. We will control for socio-cultural and environmental influences by investigating determinants of substance abuse in SCAMP, a UK cohort recruiting 6.500 11-13 year old adolescents, >1000 of which are of South Asian descent. Together these data will allow for the most comprehensive comparative analysis of brain development and behaviour across different social and cultural environments to date.