Childhood Trauma and APOEε4 are Associated with Adolescent Brain Function, Posttraumatic Stress, and Alcohol-related Outcomes

Childhood trauma affects neurodevelopment and lifelong risk for posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Changes in brain structures and function are observed in young carriers of APOEε4 , the genetic factor most associated with Alzheimer’s disease. Longitudinal studies of APOEε4 , childhood trauma, and neural connectivity in adolescence have not been explored. We studied 837 trauma-exposed participants (53% female) from the Collaborative Study on the Genetics of Alcoholism prospective sample, using latent growth curve models to assess associations of childhood trauma and APOEε4 on repeated measures of frontal alpha EEG coherence (EEGc) throughout adolescence and young adulthood. Young adult AUD and PTSD symptoms were also examined. Results indicate childhood trauma and APOEε4 are linked to neural connectivity, with effects differing by sex and trauma type. In females, sexual trauma was associated with a higher EEGc baseline but less growth, while APOEε4 associated with lower right frontocentral (RFC) EEGc baseline and higher slope. In males, physical assault was associated with lower left frontocentral (LFC) EEGc baseline but increased growth, and non-assaultive trauma was linked to a lower RFC baseline and no association with growth. APOEε4 was associated with lower LFC baseline and higher slope in males. Links between EEGc and AUD and PTSD were observed in both sexes, though effects differed in direction and strength. No significant trauma-by- APOEε4 interactions emerged, nor direct links between APOEε4 and PTSD or AUD. Findings highlight how EEGc may help explain connections between genetics, trauma, and psychopathology, guiding at-risk group identification and informing prevention strategies.