Neurocognitive and genetic influences on post-traumatic stress and risky alcohol use in trauma-exposed adolescent and young adult offspring from families enriched with Alcohol Use Disorders

Abstract

Post-traumatic stress disorder(PTSD) is a psychiatric disorder that is triggered by a stressor involving threat of death or serious injury, and is associated with symptoms of re-experiencing, avoidance, and hyper-arousal. While over half of the United States population is exposed to a traumatic event at some point in their lifetime, only 6-8% of the population will develop PTSD. Further, PTSD is associated with increased risk for adverse conditions, such as suicidal ideations, chronic pain, major depression, alcohol and other substance use disorders. Alcohol use disorders(AUDs) occur in approximately 12-30% of the population and have been associated with impaired cognitive function, physical health problems, job loss, and relationship problems. PTSD and AUD commonly co-occur, with approximately one-third of individuals with PTSD reporting a lifetime diagnosis of AUD. Individuals with PTSD and co-occurring AUD have greater cognitive impairment, worse treatment outcomes, increased risk for legal problems, higher rates of unemployment, interpersonal problems, and poor quality of life. Therefore, there is great need to better understand the etiology of co-occurring PTSD-AUD. While previous research has pointed to the multifactorial risk for these disorders, including socio-demographic characteristics, adverse life experiences, genomic and neurodevelopmental risk factors, little research has integrated data across these domains to study pathways of risk for PTSD and co-occurring AUD.

This dissertation study aimed to investigate the influence of trauma exposure, family history of AUD, and other important risk factors (i.e., sex, neurocognitive function, response inhibition, genetic vulnerability) during adolescence and young adulthood, on risk for PTSD and co-occurring AUD. This research was carried out using data from the Collaborative Studies on Genetics of Alcoholism (COGA), a deeply characterized sample of families densely affected with AUD. Overall, the findings from this dissertation demonstrate the importance of considering genetic, social environmental, and neurocognitive factors together when investigating influences of risk for the development of PTSD and co-occurring AUDs, especially during the vulnerable and critical developmental period of adolescence. These findings suggest that trauma exposure during adolescence, specifically assaultive trauma (nonsexual and sexual), influences critical aspects of executive function (e.g., response inhibition) in adulthood. Further, polygenic risk for impaired cognitive function may interact with these traumatic exposures, further impairing executive function by influencing neural processes, specifically seen through frontal theta event-related oscillations during response inhibition. Therefore, trauma-exposed adolescents with a family history of AUDs may benefit from early intervention and treatment strategies aimed at reducing the severity and endurance of PTSD and co-occurring AUD and related impaired cognitive function in adulthood.