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

在印度和其他中低收入国家，酒精使用障碍(AUD)在健康负担中所占比例高得不成比例。这一日益沉重的负担与新兴国家的社会变化有关，其中包括酒精供应的增加、使用更加正常化以及社会经济条件的快速变化。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大脑活动发生变化，患AUD的风险更高。AUD和外化障碍具有中到高的遗传率，环境因素是重要的贡献者。虽然环境和遗传因素传递风险和复原力都已确定，但尚未确定这些因素在多大程度上依赖于它们所处的更广泛的社会文化和心理社会背景，或者它们是否受到某些族裔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，环境和遗传风险因素在多大程度上相似或不同还不得而知。此外，一些环境风险因素主要是新兴社会特有的，包括暴露在营养压力、环境神经毒素和文化依赖形式的心理社会压力下。我们建议与班加罗尔国家精神健康和神经科学研究所(NIMHANS)的Vivek Benegl教授以及我们来自班加罗尔、迈索尔、加尔各答、昌迪加尔和普纳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塑造大脑功能和行为，从而导致物质滥用和外部性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，对儿童和青少年的行为轨迹进行比较分析，这为印度和英国在心理健康研究方面的持续合作提供了一个平台。该平台将确定各种环境因素(暴露组)、生物样本以及详细的神经成像分析。我们建议将从欧洲和英国的主要研究中获得的对物质滥用和外部性障碍的病因学和轨迹的见解进行比较，这些研究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。这些印度人由14.000名0-25岁的参与者组成，其中既有滥用药物的高风险人群，也有来自不同社会和环境(农村和城市)背景的人口个体。他们被选为涵盖英国队列中评估的发育时期，从而使这些研究具有可比性。我们的目标是丰富印度的队列，这些队列主要是为了调查躯体疾病，增加了对精神健康的全面评估，包括心理测量和神经心理特征的外在行为和物质使用障碍，以及对6至23岁的10.000名参与者进行生物采样。选择了评估工具和方案，以便与IMAGEN和ALSPAC进行比较。我们将从队列参与者中随机选择1000名年龄在10岁到23岁之间的人进行神经成像、遗传和表观遗传学分析。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1000人是南亚裔。这些数据结合在一起，将使迄今为止对不同社会和文化环境中大脑发育和行为的最全面比较分析成为可能。

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.