Childhood trauma heightens the risk of severe weight gain and adult obesity. However, the pathways for the increased risk of obesity in individuals exposed to early-life trauma remain poorly understood. Preclinical findings from our laboratory support the notion that cortical structural alterations and behavioral impairments, including the presence of disordered eating behavior, may account for the added risk of adult obesity. The specific goal of this study is to identify causal pathways connecting early-life trauma to aberrant eating behaviors later in life. Our strong preliminary data indicate that: 1) early-life trauma and exposure to an obesogenic diet results in marked structural impairments in the medial prefrontal cortex (mPFC), 2) early-life exposure to this obesogenic environment increases food intake and obesity-like phenotypes, and 3) these environmental conditions alter the levels and signaling of the growth factor neuregulin-1 (NRG1). Based on this strong preliminary data, we hypothesize that overactivation of NRG1 signaling in the prefrontal cortex contributes to the effects of early-life traumatic stress on dendritic spine loss, synaptic density, and aberrant cortical network maturation and feeding patterns, promoting rapid weight gain and obesogenic phenotypes during adulthood. We propose to pursue two Specific Aims to identify neural substrates and molecular mechanisms impacted by early-life environmental adversities: 1) we will use translational and innovative diffusion imaging modalities (NODDI) and SV2A-based positron emission tomography (PET) to determine the longitudinal effects of early-life trauma on mPFC subfield microstructure and synaptic densities; 2) identify molecular mechanisms by which early-life trauma attenuates optimal neurotrophic support, resulting in aberrant control of feeding behaviors (increased intake and palatable food preference). This proposal will have a significant positive impact because it will identify early and subtle microstructural vulnerabilities and neuroimaging biomarkers to trauma exposure. Furthermore, the experiments outlined in this exploratory proposal will contribute to enhancing our understanding of the underlying convergence neuropathology and molecular pathways linking early-life trauma to disordered feeding behaviors and obesity. Having a better understanding of these adaptations may contribute to the identification of new opportunities to prevent and treat the long-term impact of childhood adversities on physical and mental health outcomes.
Substantial evidence documents an association between childhood trauma and the development of obesity across the life course. This translational study identifies potential behavioral, neuroanatomical, and molecular adaptations mediating the elevated risk of obesity in persons exposed to early-life trauma. Having a better understanding of early brain responses to trauma may contribute to innovative preventative, curative, and disease-modifying approaches for obesity.
