1. Trauma Exposure, PTSD, and Alcohol Use Among Emerging Adults Ananda Amstadter, PhD Virginia Institute for Psychiatric and Behavioral Genetics

3. Trauma TypeFemalesMalesTotal Sexual Victimization (pre VCU) 29.3%*10.9%22.2% Physical Assault (pre VCU) 21.0%28.9%*24.1% Sexual Victimization (since VCU) 23.0%*11.6%18.7% Physical Assault (since VCU) 9.3%12.4%*10.5% Sexual Victimization (revictimization) 40.6%33.5% 39.2 % Physical Assault (revictimization) 16.0%20.0% 17.4% (Overstreet, Hawn, Conley, Kendler, Dick*, Amstadter*, under review; *co-last) (Conley, Overstreet, Hawn, Kendler, Dick*, Amstadter*, under review; *co-last)

4. Posttraumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD) PTSD Criterion A: Stressor Intrusions Avoidance Negative Alterations in Cognitions and Mood Alterations in Arousal and Reactivity Duration >1 month Function Impairment Distress AUD Drank more than intended Wanted to cut down Spent a lot of time drinking Craving Interference with life Drank despite problems Given up on desired activities Drinking increased harm Continued to drink even if it made one feel depressed/anxious Tolerance Withdrawal DSM-V

5. Trauma Exposure is Associated with Psychiatric Disorders OR=3.21 OR=2.90 OR=2.80 OR=2.82 National Survey of Adolescents

6. PTSD OR (95% CI) Alcohol Abuse OR (95% CI) Gender2.31 (1.67-3.19)1.14 (.84-1.54) Race/Ethnicity1.08 (.78-1.49)1.31 (.95-1.82) Income1.03 (.97-1.10)1.07 (1.01-1.15) Sexual Assault2.86 (1.97-4.15)1.77 (1.17-2.66) Physical Assault3.61 (2.60-5.00)3.09 (2.24-4.25) Witnessed Violence3.27 (2.30-4.65)3.18 (2.26-4.47) Other trauma1.42 (1.04-1.94)1.45 (1.07-1.97) National Survey of Adolescents

7. PTSD and Alcohol Use Disorder Comorbidity Nearly half of those seeking treatment for an AUD meet current criteria for PTSD (Brown et al., 1999), an estimate more than five times greater than the lifetime prevalence 52% of adult males and 30% of adult females with PTSD also have an AUD (Kessler et al., 1995) PTSD was associated with a nearly 4 fold increased risk for AUD in young adults (Amstadter et al., 2014) Also shown in youth: 30% of adolescent males and 24% of adolescent females with PTSD also have a substance use disorder (Kilpatrick et al., 2003)

8. Models of Comorbidity Self-medication hypothesis Drinking to cope PTSD should precede AUD AUD may increase risk for PTSD AUD will increase likelihood of trauma Withdrawal is associated with anxiogenic withdrawal symptoms that increase PTSD symptoms after trauma exposure Third variable hypothesis Shared genetic risk Trauma exposure itself may increase risk

9. Test of the 3 Models in Adolescents NSA-R; youth ages 12-17, n=3,614 assessed three times approximately one year apart Cumulative trauma, PTSD, Alcohol use quantity and frequency to determine binge drinking Parallel process latent growth curve models demonstrated: Cumulative trauma over time predicted increased PTSD and binge drinking PTSD and binge drinking were NOT prospectively related when controlling for trauma exposure Regardless of direction of causation, only significant when not controlling for trauma exposure Specific to interpersonal trauma Does not support self-medication or AUD-> PTSD models Third variable explanation: cumulative trauma exposure may have effects on neurobiological mechanisms that mediate vulnerability for both phenotypes Shared genetic vulnerability? (Cisler, Begle, Resnick, Danielson, Saunders, Kilpatrick, & Amstadter, 2012)

10. Trauma, PTSD, and Alcohol Use among VCU: S4S Spit for Science - 1,197 students were included in analyses (68.0% female). Students were assessed at the beginning of college, then each spring semester for two years Quantity and frequency of alcohol use, traumatic events, and probable PTSD status Linear growth curve models demonstrated: Pre-college interpersonal PTE was associated with greater initial alcohol use for female but not male students. College-onset interpersonal PTE predicted greater alcohol use at concurrent and future assessments for female but not male students, above and beyond the effects of pre-college interpersonal PTE. Pre-college probable PTSD did not predict initial level of alcohol use or alcohol trajectories. There may be a stronger and longer-lasting impact of interpersonal PTE for college women compared to men on alcohol phenotypes The results highlight the need for secondary prevention to reduce the likelihood of negative outcomes such as problem drinking among college women impacted by interpersonal PTE. (Berenz*, Cho*, Overstreet, Kendler, Amstadter*, & Dick*, 2015; co-first/last)

11. Disaster Exposed Adolescents 704 youth, 12-17 were assessed for severity of trauma, PTSD, and binge drinking after a tornado, and a genetic risk sum score was computed for alcohol-phenotypes PTSD symptoms mediated the effect of severity of exposure on drinking Consistent with literature on self-medication Higher genetic risk was associated with binge drinking Genetic risk moderated the effect of PTSD symptom on drinking (effect was strongest for those at or above the mean of genetic risk) Self-medication may be stronger for those with a greater propensity for alcohol misuse Past Month Binge Drinking Severity of Tornado- related Exposure Adolescent PTSD symptoms Baseline Four-Month Follow-Up Twelve-Month Follow- Up Adolescent Genetic Risk (Bountress, Tomko, Danielson, Williamson, Vladimirov, Gelernter, Ruggiero, & Amstadter, under review)

12. Conclusions and Implications Across all three longitudinal studies the cumulative effect of trauma was related to both PTSD and alcohol outcomes, suggesting that secondary prevention among trauma exposed individuals is key This was demonstrated to be IPV specific in the first two studies, but found in a non-IPV sample when trauma severity was measured Trauma exposure, especially during sensitive developmental windows, may have effects on neurobiologic systems related to both PTSD and AUD Additional mechanistic studies are needed Genetic risk may moderate the effect of PTSD symptoms on alcohol outcomes Self-medication may be more pronounced for those at genetic risk alcohol outcomes, suggesting the need for multimodal studies

13. Collaborators Bounce Back Now Ken Ruggiero Kaitlin Bountress Carla Danielson Joel Gelernter Vlady Vladimirov Vernell Williamson And others Spit for Science Danielle Dick Ken Kendler Erin Berenz Bin Cho Cassie Overstreet Sage Hawn Abigail Conley And many more! National Survey of Adolescents Josh Cisler Dean Kilpatrick Ken Ruggiero Heidi Resnick Carla Danielson Angie Moreland I am supported by grants R01AA020179, K02 AA023239, BBRF 20066, R21 MH103686, R01MH101518, and P60MD002256.