title: Neuroactive steroids and PTSD treatment.
abstract: This review highlights early efforts to translate pre-clinical and clinical findings regarding the role of neuroactive steroids in stress adaptation and PTSD into new therapeutics for PTSD. Numerous studies have demonstrated PTSD-related alterations in resting levels or the reactivity of neuroactive steroids and their targets. These studies also have demonstrated substantial variability in the dysfunction of specific neuroactive steroid systems among PTSD subpopulations. These variabilities have been related to the developmental timing of trauma, severity and type of trauma, genetic background, sex, reproductive state, lifestyle influences such as substance use and exercise, and the presence of comorbid conditions such as depression and chronic pain. Nevertheless, large naturalistic studies and a small placebo-controlled interventional study have revealed generally positive effects of glucocorticoid administration in preventing PTSD after trauma, possibly mediated by glucocorticoid receptor-mediated effects on other targets that impact PTSD risk, including other neuroactive steroid systems. In addition, clinical and preclinical studies show that administration of glucocorticoids, 17β-estradiol, and GABAergic neuroactive steroids or agents that enhance their synthesis can facilitate extinction and extinction retention, depending on dose and timing of dose in relation to these complex PTSD-relevant recovery processes. This suggests that clinical trials designed to test neuroactive steroid therapeutics in PTSD may benefit from such considerations; typical continuous dosing regimens may not be optimal. In addition, validated and clinically accessible methods for identifying specific neuroactive steroid system abnormalities at the individual level are needed to optimize both clinical trial design and precision medicine based treatment targeting.
authors.affiliation: National Center for PTSD, Women's Health Science Division, Department of Veterans Affairs 150 South Huntington Avenue, Boston, MA 02135, USA; VA Boston Healthcare System 150 South Huntington Avenue, Boston, MA 02135, USA; Boston University School of Medicine 72 E Concord St, Boston, MA 02118, USA. Electronic address: ann.rasmusson@va.gov.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rasmusson
authors.affiliation: Durham VA Medical Center, VA Mid-Atlantic MIRECC,and Duke University Medical Center, 508 Fulton Street, Durham, NC 27705, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Marx
authors.affiliation: National Center for PTSD, Women's Health Science Division, Department of Veterans Affairs 150 South Huntington Avenue, Boston, MA 02135, USA; Boston University School of Medicine 72 E Concord St, Boston, MA 02118, USA.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Pineles
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor Str., Chicago, IL 60612, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Locci
authors.affiliation: VA Boston Healthcare System 150 South Huntington Avenue, Boston, MA 02135, USA; Boston University School of Medicine 72 E Concord St, Boston, MA 02118, USA.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Scioli-Salter
authors.affiliation: National Center for PTSD, Women's Health Science Division, Department of Veterans Affairs 150 South Huntington Avenue, Boston, MA 02135, USA; Boston University School of Medicine 72 E Concord St, Boston, MA 02118, USA.
authors.forename: Yael I
authors.initials: YI
authors.lastname: Nillni
authors.affiliation: Boston University School of Medicine 72 E Concord St, Boston, MA 02118, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Liang
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor Str., Chicago, IL 60612, USA.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pinna
mesh_terms: D000818:Animals; D003687:Dehydroepiandrosterone / Q000502:physiology / Q000627:therapeutic use; D004958:Estradiol / Q000502:physiology / Q000627:therapeutic use; D005938:Glucocorticoids / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D011280:Pregnanolone / Q000502:physiology / Q000627:therapeutic use; D013256:Steroids / Q000502:physiology* / Q000627:therapeutic use*; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy*
chemical_list: D005938:Glucocorticoids; D013256:Steroids; D003687:Dehydroepiandrosterone; D004958:Estradiol; D011280:Pregnanolone
keywords: 3α-hydroxysteroid dehydrogenase; 5α-Reductase type I and type 2; Allopregnanolone; Cortisol; Dehydroepiandrosterone; Endocannabinoids; GABA(A) receptors; Neuroactive steroids; Posttraumatic stress disorder (PTSD); Pregnanolone; Selective brain steroidogenic stimulants (SBSSs); TSPO ligands