This proposal addresses one of the most pervasive and pernicious stressors in society - the problem of child abuse and neglect. The unacceptably high prevalence and the severe short- and long-term mental and physical health consequences across the entire lifespan of exposure to child abuse and neglect (early life stress; ELS) is well established. Growing evidence suggests that the consequences of ELS exposure are not restricted to the exposed girl/woman alone but also may be transmitted to her offspring. Children of women with ELS exposure are at higher risk for neurodevelopmental and psychiatric disorders. The time windows (when) and the biological processes (how) underlying this trans-generational transmission are poorly understood. This critical knowledge gap will be addressed in the current proposal. Our model proposes that (a) the effects of maternal ELS exposure on child neurodevelopmental outcomes start as early as during the child?s intrauterine life and extend through infancy; (b) the effects are mediated via i) direct actions of ELS-associated changes in maternal-placental-fetal endocrine and immune stress physiology on the developing fetal brain and ii) indirect actions of ELS-associated changes in maternal oxytocinergic physiology in pregnancy on subsequent maternal parenting behaviors and mental state (e.g., postpartum depression); and (c) the molecular underpinnings of these effects are a consequence of the stable and enduring alterations produced by ELS exposure on the expression of candidate maternal, placental and fetal/infant genes via alterations in DNA methylation of hormone response elements in transcriptional regions. Our proposed translational and transdisciplinary project takes advantage of two ongoing, funded, complementary population-based longitudinal cohort studies of pregnancy, birth and infancy in Irvine, California, and Helsinki, Finland, that provide the requisite clinical data, biological samples and neurodevelopmental phenotypes, thereby ensuring substantial time- and cost-efficiency. The scientific significance of our proposal pertains to an understanding of the biological pathways and mechanisms that may underlie the trans-generational transmission of the effects of ELS from this vulnerable population of women to the even more vulnerable population of their children, whereas the clinical significance relates to risk identification and the eventual development of early interventions before the occurrence of biological embedding of adverse maternal experience in her developing child.
Imaging techniques, Behavioural methodologies, (epi)genetic approaches, aetiology, transgenerational transmission, childhood trauma, fetal programming, susceptibility for psychiatric disorders, stress-related disorders