ALCOHOL PTSD COMORBIDITY CONCEPT CLEARANCE Dr. Lindsey Grandison

Title: Alcohol-PTSD Comorbidity: Preclinical Studies of Models and Mechanisms Rationale: PTSD is a psychological disorder with a high prevalence (an estimated 7% life time incidence, the 4th most common psychiatric disorder), a persistence that can last a life time and a substantial mental health burden. Alcohol use disorders occur in 30% of PTSD subjects and can occur at a much higher rate in specific populations of PTSD patients. Investigation of the comorbid PTSD – alcohol use disorders condition would provide insight into the link by which PTSD increases the risk for alcohol dependence as well as identify the neurobiological processes common to both PTSD and alcohol use disorders. Development and validation of animal models of PTSD/AUD comorbidity may lead to interventions to prevent the progression from PTSD to comorbid PTSD-AUD and to effective treatments for this refractory condition. Symptom severity is greater with comorbidity and treatment is more difficult It is estimated that 70% of the population will be exposed to some form of trauma. Approximately 20% of trauma exposed subject develop PTSD. PTSD - an adverse response that persists for an extended period and that compromises functioning including intrusive re-experiencing of the traumatic experience, avoidance of cues that are associated with the trauma, numbing a state of hyperarousal. Duration of symptoms – persistence of symptoms for more than one month Significant distress or functional impairment in social, occupational or other contexts Thirty to sixty percent of patients seeking treatment for alcohol use disorders meet criteria for PTSD Half of individuals with PTSD-alcohol dependence experienced their first period of alcohol dependence within the first year of PTSD or later after the development of PTSD

Potential areas of investigation: •Assessment of alcohol consumption in a well characterized animal model of PTSD. This would examine alcohol consumption in animals with no compulsive-like responding for alcohol prior to development of PTSD; prior exposure to nondependent drinking may be necessary to avoid the initial taste-aversion-like response to alcohol in rodents. •Characterization of the impact of an adverse, early life experience on development in adulthood of PTSD-AUD comorbidity in response to a trauma. •Determine the effect of alcohol exposure on the development of PTSD and the subsequent intake of alcohol after PTSD development. For alcohol exposure prior to PTSD, moderate drinking (BAL <80 mg%), binge (BAL >80 mg%) and alcohol dependent or compulsive-like levels of consumption may be considered. •Assess the effect of sex on development of PTSD/AUD comorbidity and if observed, distinguish the impact of gonadal hormones from chromosomal sex composition. •Characterize the role of neuroimmune activation in PTSD/AUD comorbidity. •Identify the neurobiological processes, neurobiological targets for potential treatment, and/or the biomarkers that will predict transition of PTSD to comorbid PTSD-alcohol misuse. Investigation is not limited to these topics. All relevant proposals would be considered.