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

• Published in: Frontiers in neuroendocrinology Vol. 73; p. 101119
• Main Authors: Peltier, MacKenzie R., Verplaetse, Terril L., Altemus, Margaret, Zakiniaeiz, Yasmin, Ralevski, Elizabeth A., Mineur, Yann S., Gueorguieva, Ralitza, Picciotto, Marina R., Cosgrove, Kelly P., Petrakis, Ismene, McKee, Sherry A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2024
• Subjects: Alcohol use disorder; Alcoholism - drug therapy; Alcoholism - metabolism; Animals; Female; Humans; Male; Neurosteroids; Neurosteroids - metabolism; Posttraumatic stress disorder; Sex as a biological variable; Stress Disorders, Post-Traumatic - drug therapy; Stress Disorders, Post-Traumatic - metabolism; Posttraumatic stress disorder; Alcohol use disorder; Neurosteroids; Sex as a biological variable
• ISSN: 0091-3022; 1095-6808; 1095-6808
• DOI: 10.1016/j.yfrne.2023.101119

•Neurosteroids are implicated in the underlying mechanisms of PTSD/AUD and are potential treatments.•Pregnenolone, progesterone & allopregnanolone have the most support for PTSD and AUD.•Few studies have explored the role of neurosteroids for PTSD and AUD concurrently.•There is an inconsistent application of SABV which warrants more rigorous research. 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.