The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.

Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development. This review details the past ten years of research on pregnenolone, progesterone, allopregnanolone, pregnanolone, estradiol, testosterone and dehydroepiandrosterone/dehydroepiandrosterone-sulfate (DHEA/DHEA-S) in the context of PTSD and AUD, including examination of trauma/alcohol-related variables, such as stress-reactivity. Emerging evidence that exogenous pregnenolone, progesterone, and allopregnanolone may be promising, novel interventions is also discussed. Specific emphasis is placed on examining the application of sex as a biological variable in this body of literature, given that women are more susceptible to both PTSD diagnoses and stress-related alcohol consumption.

An experimental laboratory-based minority stress paradigm for alcohol research among sexual minority women: A pilot study.

BACKGROUND: Sexual minority women (SMW) use alcohol at higher rates and experience greater alcohol-related harms than their heterosexual counterparts. Evidence from observational studies suggests that minority stress (i.e., stress experienced due to marginalization in society) is an important risk factor among SMW, yet there is a lack of experimental evidence to establish a direct causal role of minority stress on alcohol use in this population. We adapted the preexisting personalized guided stress induction paradigm to conduct a pilot study of how minority stress is related to stress response (assessed via subjective measures and salivary cortisol) and mechanisms of alcohol use (craving, demand, and risky decision making) in SMW. METHODS: Using a within-subjects design (N = 8) cisgender SMW who endorsed high-risk drinking (≥1 heavy drinking episode in the past 30 days) completed three study visits: a script development session and two in-person imagery induction appointments (minority stress and neutral). Analyses examined feasibility and acceptability, stress response, and mechanisms of alcohol use. RESULTS: The paradigm significantly increased subjective stress response (g = 1.32). Data supported the feasibility, acceptability, and appropriateness of the paradigm for use with SMW. While the paradigm did not significantly change scores on minority stress and alcohol outcomes measures, effect sizes for craving and minority stress outcomes were in the small-to-medium range (gs = 0.24-0.54). CONCLUSIONS: The adapted minority stress paradigm appears to be feasible and appropriate for use with SMW to induce stress in laboratory settings. Future research can use this paradigm to understand the causal effects of minority stress on alcohol use and related outcomes.