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

在印度和其他低收入和中等收入国家，酒精使用障碍在健康负担中所占的比例过高。这一日益加重的负担与新兴国家的社会变化有关，其中包括酒精供应日益增加、酒精使用更加正常化以及社会经济条件的迅速变化。具有外化行为的个体，其特征是在奖励处理和行为控制过程中改变了大脑活动，患AUD的风险更高。AUD和外化障碍具有中等至高的遗传性，环境因素是重要的因素。虽然已经确定了传递风险和复原力的环境和遗传因素，但尚未确定这些因素在多大程度上取决于它们所处的更广泛的社会文化和社会心理环境，或者它们是否受到某些种族特有的表观遗传和遗传因素的影响。因此，在工业化国家和印度等新兴社会中，环境和遗传风险因素的相似或不同程度是未知的。此外，一些环境风险因素在很大程度上是新兴社会特有的，包括暴露于营养压力、环境神经毒素和文化依赖形式的社会心理压力。我们建议与班加罗尔国家心理健康和神经科学研究所（NIMHANS）的Vivek Benegal教授以及来自班加罗尔、迈索尔、加尔各答、昌迪加尔和浦那的印度合作伙伴合作，调查工业化国家和新兴社会的环境和遗传风险因素是否以不同的方式影响大脑功能和行为。从而导致药物滥用和外化障碍的不同风险星座和神经行为轨迹。为了实现这一目标，我们将建立一个全面的数据库，以便对儿童和青少年的行为轨迹进行比较分析，这将为印度和英国在心理健康研究方面的持续合作提供一个平台。该平台将确定各种环境因素（暴露），生物样本以及详细的神经成像分析。我们建议比较从欧洲和英国的主要研究中获得的关于药物滥用和外化障碍的病因学和轨迹的见解，包括纵向成像遗传学研究“正常发育和精神病理学中的强化相关行为”（IMAGEN）和“雅芳父母和儿童纵向研究”（ALSPAC）与现有的印度队列。印度队列包括14000名年龄在0-25岁之间的参与者，其中既有药物滥用的高风险人群，也有来自不同社会和环境（农村和城市）背景的人群。他们被选择来涵盖在英国队列中评估的发展期，从而使研究具有可比性。我们的目标是丰富印度队列，这些队列主要是通过增加对心理健康、外化行为和物质使用障碍的综合评估来调查躯体疾病，包括心理测量学和神经心理学特征，以及对10万名年龄在6-23岁之间的参与者进行生物抽样。已选择评估工具和方案，以便与IMAGEN和ALSPAC进行比较。我们将在队列参与者中随机选择1000名年龄在10至23岁之间的个体进行神经影像学、遗传学和表观遗传学分析。我们将通过调查SCAMP中药物滥用的决定因素来控制社会文化和环境的影响，SCAMP是一个英国队列，招募了6,500名11-13岁的青少年，其中1,1000名是南亚血统。综合这些数据，可以对迄今为止不同社会和文化环境下的大脑发育和行为进行最全面的比较分析。

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.