About the cVEDA study

The Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA) is jointly funded by the Indian Council for Medical Research (ICMR) and the Newton Grant from the Medical Research Council (MRC), United Kingdom. Principal Investigators for this study are Professor Gunter Schumann, King’s College London (KCL; London, UK) and Dr Vivek Benegal, National Institute of Mental Health and Neurosciences (NIMHANS; Bangalore, India). Project coordinators are Ms Yuning Zhang (London) and Ms Nilakshi Vaidya (India). The India-UK project is an international collaboration between Prof Gunter Schumann at King’s College London and Prof Vivek Benegal of the National Institute for Mental Health and Neurosciences (NIMHANS), Bangalore and our Indian partners from Bangalore, Mysore, Calcutta, Chandigarh and Manupur. Our aim is to investigate 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 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.

c-VEDA is funded by an MRC-ICMR Newton Grant to Gunter Schumann and Vivek Benegal.

Project Aims

The aim of the project is to accumulate a developmental cohort of children, adolescents and young adults, gathered from 1] existing birth cohorts and 2] children at risk for addiction, in India, so that we may enrich the existing data on birth, parental and perinatal information, growth parameters with longitudinal data on brain development , temperament and behaviour, as well as information regarding gene x environment influences, in order to create a data repository and biobank, which will enable prospective follow-up of these subjects through the developmental life-span and the study of gene x environment mediated development of states which increase risk or resilience to addictive disorders and associated psychiatric disorders.

To achieve this aim, this project incorporates and integrates FOUR sub-projects, which involve the development of:

• A high Risk Cohort of children, adolescents and young adults deemed at-risk for addictive disorders due to high family loading for addictive disorders to be recruited from offspring of persons seeking treatment for substance use disorders;
• An Exposures Cohort of children, adolescents and young adults in the general population who are exposed to different environmental risk factors during the developmental period;
• A Repository to accumulate data pertaining to the above enquiries and a bio-resource to facilitate immediate and long-term research studies;
• An Exposures Cohort of children, adolescents and young adults in the general population who are exposed to different environmental risk factors during the developmental period – specially situated in the North-eastern part of India with specific funding set aside for Building Human Resource Capacity with Training.

Objectives

• Establish an accelerated and planned missing longitudinal cohort in India of over 10,000 individuals within specific age ranges 6-11, 12-17, 18-23 years, by enriching existing birth cohorts and high risk cohorts (offspring of treatment seeking alcohol and other substance dependent patients).
• Assess addictive behaviour, in adolescents and young adult members of the cohort and in parents of all subjects, both substance-based and behavioural, and carrying out a detailed behavioural characterization, with special emphasis on externalising behaviour (temperament and disorders), as well as a clinical assessment according to DSMV/ICD10.
• Assess environmental exposures in utero and through the developmental span to select risk and resilience factors, including psychosocial stressors, socioeconomic status, societal discrimination, food and asset security, physical activity, nutrition and environmental toxins, which are thought to impact gene expression, brain development and eventually temperaments and behaviours.
• Assess neural processes associated with externalising behaviours and addictions using functional and structural neuroimaging in a randomly selected deep phenotyping subgroup of 1000 individuals.
• Investigate gene x environment-mediated modulation of brain development, and externalising and addictive behaviour through genetic and epigenetic studies in the deep phenotyping subset.
• Establish a sustained and accessible data platform including a bio-resource with integrated database and bio-bank to facilitate analyses by consortium partners as well as collaborators investigating other areas of mental health, and its interface with physical health.
• Build capacity by joint UK – Indian analysis teams, technology transfer, training sessions and summer schools, dedicated neuroimaging and bio-statistical support teams as well as the provision of short-term fellowships.
• Provide pilot data for the establishment of a nationwide mental health cohort in India.

The multiple recruitment and acquisition centres of c-VEDA cover 6 geographical regions across both urban and rural India representing the socio-cultural diversity of India.

National Institute of Mental Health and Neurosciences, Bangalore

The National Institute of Mental Health and Neurosciences is the leading Indian collaborator on the cVEDA study. The Centre for Addiction Medicine at NIMHANS, Bangalore, headed by Dr Vivek Benegal (Principal Investigator for cVEDA), is the Regional Centre for the southern region, under the National Drug Deaddiction Programme of the Ministry of Health and Family Welfare, Government of India. This centre runs outpatient and inpatient services, and caters to around 100 patients per week. The center has a strong focus on research since its inception. The research directions have been shaped, both by its location as well as the research interests of the individual faculty. A major direction has been the study of the prevalence and patterns of alcohol, tobacco and other drug use in India. This has included initiating some of the first enquiries in the country, on patterns of use, economic consequences and social cost of alcohol, normative use of alcohol among women and substance use in special risk groups which have contributed to the growing acceptance of substance use especially alcohol as a critical public health problem in India. The other significant direction has been the study of genetic and neurobiological factors which underlie the susceptibility to addiction, especially in young people.

The research group for cVEDA at NIMHANS, led by Dr Benegal, has accumulated data on various endophenotypes of vulnerability to addictive disorders and other mental illnesses, including measures of brain volume, white matter integrity, cognitive functions and genetic variants associated with addiction and mental illnesses. Subjects will be drawn from among the children of this large patient cohort at this site.

St. John’s Research Institute, Bangalore