Mechanisms of Early Adversity Associated Increases In Risk For Psychiatric Disorders

Abstract

Overall Abstract Early adverse exposures, such as maternal stress or toxins during pregnancy and childhood adversity are thought to result in long-lasting consequences on many systems, including the brain and ultimately in an increased risk for psychiatric disorders. The impact of these environmental risk factors is moderated by genetic variation. The biological mechanisms underlying this increased risk are still unclear. This symposium will focus on potential mechanisms mediating these lasting effects and their moderation by genetic variation, with epigenetics, specifically DNA methylation as main candidate. The developing brain is highly sensitive to environmental exposures during the in utero period and three of the presentations will focus on how environmental factors during pregnancy alter risk for psychiatric symptoms as well as brain structure and function and have lasting influences on the epigenome at birth. Prenatal exposures such as cigarette smoke, heavy metals, and folic acid are associated with changes in DNA methylation measured in infants at birth Kelly Bakulski (University of Michigan) will report on data generated in an autism enriched-risk birth cohort that examines the sensitivity of DNA methylation at birth, measured in placental tissue and cord blood, to in utero environmental exposures and the development of autism spectrum disorder or related traits by age three. Margit Burmeister (University of Michigan) will present a study of iron deficiency in newborns in China, demonstrating the detrimental effects of pre-and postnatal iron deficiency with regards to brain structure and function. This is complemented by genome-wide epigenetic analyses that investigate the impact of iron deficiency in the presence of lead exposure and pesticides. Another set of pregnancy-related risk factors associated with increased risk for emotional and behavioral problems in children are stress and depression during pregnancy. Katri Raikkonen (University of Helsinki, Finland) will present data from a large prospective study of pregnancy risk factors and their effects on cord blood DNA methylation and child behavior up to 3.5 years of age. Maternal depression during pregnancy was related to significant changes in a recently established epigenetic predictors of gestational age, with increasing depression, associated with more “immature” epigenetic age. This epigenetic marker was then in turn predicting total behavioral, emotionally reactive, and withdrawn problems in boys. Finally, risk for psychiatric symptoms following exposure to childhood adversity is moderated by genetic variation. Understanding the mechanisms of this moderation may help in targeting specific treatments to children with combined genetic and environmental risk. Sara Jaffee (University of Pennsylvania) showed that 8- to 11-year-old children from the UK who carried two copies of the serotonin transporter polymorphism had elevated levels of internalizing and externalizing problems following exposure to adverse life events because of their coping strategies. Influencing the coping styles of these children may be an effective treatment strategy in this subgroup of children. At the end of the symposium, Elisabeth Binder (MPI of Psychiatry, Munich) will comment of common mechanisms emerging from the data presented in the individuals talk and how a better understanding of these factors will aid biology-based diagnoses of psychiatric disorders and individualized treatment approaches.