Intergenerational Transmission of Risk for Common Mental Disorders: A Longitudinal Extended Children-of-Twins Cohort Study

Mental disorders affect 10-20% of children and adolescents worldwide, and are one of the leading causes for disability in adults. Common mental disorders (CMD) in both children (e.g. anxiety disorders, depression, conduct disorder, and ADHD) and adults (e .g. anxiety disorders, depression, substance use disorders, antisocial personality disorder, and adult ADHD) can be divided into an Internalizing and an Externalizing spectrum. Externalizing disorders are characterized by a general risk for disinhibitory behavior, and from adolescence also include disorders such as substance use and antisocial behavior disorders. Internalizing disorders include disorders such as major depressive disorder, generalized anxiety disorder, and different phobias. There is a strong association between CMD in parents and children, and a CMD in parents is found to be the most important risk factor for the same disorder in children. Associations between CMD in parents and children could be due to three different modes of intergenerational transmission of risk: 1) risk genes shared among family members, 2) risk environments shared among family members, and 3) direct effect of CMD in parents which leads to CMD in children. The objective of this project was to prospectively study genetic and environmental modes of intergenerational transmission of risk from CMD and alcohol use in parents to CMD in children. Our aim was thereby to contribute to clarifying the causal mechanisms underlying these disorders. Such knowledge is a necessary foundation for the development of effective prevention and treatment strategies. Theories and claims about causal processes involved in CMD shape and guide public policy with regard to prevention efforts, and treatment. It is therefore of great importance to clarify the underlying etiological mechanisms. Choice of prevention and intervention strategies based on either of the modes of risk transmission between parents and children would be very different. Several results have been disseminated during the Project period. First, an article on the excess rates of depression in twin mothers. This is important ground work for further twin studies. Second, a method paper on how to improve estimation in genetic models using prior information. Third, the first study on parental alcohol use, where there was an association between maternal heavy alcohol use on both internalizing and externalizing problems in the offspring, but these effect disappeared after adjusting for time-invariant familial confounding. Such factors represent genetic factors and familial environment. Last, a sibling control study on a putative mediator of maternal depression during pregnancy and offspring internalizing and externalizing problems: antidepressant medication. The project members held several talks on national and international seminars and conferences. By the end of the Project period members have several papers in revision that is expected to be published soon. The PhD student of the project had in 2016 a very successful overseas stay at Virginia Commonwealth University, and handed in his thesis in December 2017.

The primary objective of this project is to prospectively study genetic and environmental modes of intergenerational transmission of risk from common mental disorders (CMD) and alcohol use in parents to CMD in children. Our aim is thereby to contribute to clarifying the causal mechanisms underlying these disorders. Such knowledge is a necessary foundation for the development of effective prevention and treatment strategies. The strongest predictor of a mental disorder in childhood is to have a parent wit h the same disorder. However, simple epidemiological associations are ambiguous with regard to causality. Associations between CMD in parents and children could be due to three different modes of intergenerational transmission of risk: 1) risk genes share d among family members, 2) risk environments shared among family members, and 3) direct effect of CMD in parents which leads to CMD in children (direct environmental). We will use data from a large population-based longitudinal cohort of twins and full s iblings and their children, followed from week 17 in pregnancy to 5 years after birth, to estimate the mode of intergenerational transmission of risk for CMD. Specifically, we aim to estimate: 1) the transmission of risk from externalizing problems in par ents (i.e. maternal alcohol use and parental symptoms of ADHD) to child internalizing and externalizing disorders including symptoms of ADHD in early childhood; 2) the transmission of risk from internalizing disorders (anxiety and depression) to child in ternalizing and externalizing disorders in early childhood. Theories and claims about causal processes involved in CMD shape and guide public policy with regard to, prevention efforts, and treatment. It is therefore of great importance to clarify the und erlying etiological mechanisms. Choice of prevention and intervention strategies based on either of the modes of risk transmission between parents and children would be very different.