PROJECT SUMMARY
Approximately 30% of the population will meet criteria for an alcohol use disorder (AUD) in their lifetime,
making it the most prevalent substance use disorder in the United States. Posttraumatic stress disorder
(PTSD), a condition characterized by symptoms of re-experiencing, avoidance, and hyper-arousal following a
traumatic exposure, is present in approximately 6-8% of the general population, and has high comorbidity with
AUD. Additionally, individuals with a family history of AUD have a disproportionately high rate of trauma
exposure and both subsequent PTSD and AUD as compared with the general population, which suggests that
other factors, including genetic, social environmental, and neurocognitive influences, may increase the risk for
trauma exposure, posttraumatic stress disorder, and co-occurring AUD. However, no study to our knowledge
has examined the influence of these factors together, using multiple assessments prospectively measured
throughout adolescence and young adulthood. We hypothesize that trauma-exposed adolescents and young
adults with a family history of AUD will have a higher risk for later PTSD and/or comorbid AUD than trauma-
exposed subjects without a family history of AUD, and that these individuals will show less efficient cognitive
functioning (i.e., response inhibition). In addition, we hypothesize that genetic risk variants influencing
cognitive function may also influence risk for PTSD and/or AUD. We will address these hypotheses through
the following Specific Aims: 1) examine the interaction of trauma exposure and family history of AUD on risk for
PTSD and comorbid AUD across adolescence and young adulthood; 2) examine the interaction of family
history of AUD and trauma exposure on neurocognitive function and behavior during a response inhibition task
across adolescence and young adulthood; and 3) examine if genetic risk variants influencing neurocognitive
function also influence PTSD and/or AUD risk. Data from the Collaborative Study on the Genetics of
Alcoholism (COGA) prospective study (N=3,812) at two-year intervals (baseline and 3 follow-ups) will be
utilized to conduct longitudinal analyses assessing differences in DSM-IV PTSD symptoms/diagnosis, alcohol
dependence symptoms/diagnosis, and neurocognitive functioning. Genetic variants meeting significance
criteria in the Cognitive Genomics Consortium's recently published genome-wide association study (N=35,298)
will be tested for association with risk for PTS and comorbid AUD. Findings from this research proposal could
inform early intervention and treatment strategies aimed at reducing the severity and endurance of PTSD and
AUD.
