Neuroactive steroids and PTSD treatment

NEUROSCIENCE LETTERS

卷:649

Review

Rasmusson, Ann M.^1,2,3  Marx, Christine E.^4,5  Pineles, Suzanne L.^1,3  Locci, Andrea⁶  Scioli-Salter, Erica R.^2,3  Nillni, Yael I.^1,3  Liang, Jennifer J.³  Pinna, Graziano⁶ 

[1] US Dept Vet Affairs, Natl Ctr PTSD, Womens Hlth Sci Div, 150 South Huntington Ave, Boston, MA 02135 USA

[2] VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02135 USA

[3] Boston Univ, Sch Med, 72 E Concord St, Boston, MA 02118 USA

[4] Durham VA Med Ctr, VA Mid Atlantic MIRECC, 508 Fulton St, Durham, NC 27705 USA

[5] Duke Univ, Med Ctr, 508 Fulton St, Durham, NC 27705 USA

[6] Univ Illinois, Dept Psychiat, Inst Psychiat, 1601 W Taylor Str, Chicago, IL 60612 USA

关键词: Neuroactive steroids;    Allopregnanolone;    Cortisol;    Dehydroepiandrosterone;    Pregnanolone;    5 alpha-Reductase type 1 and type 2;    3 alpha-hydroxysteroid dehydrogenase;    GABA(A) receptors;    Selective brain steroidogenic stimulants (SBSSs);    Endocannabinoids;    TSPO ligands;    Posttraumatic stress disorder (PTSD);   

DOI  :  10.1016/j.neulet.2017.01.054

来源: Elsevier

【 摘 要 】

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, 17 beta-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. (C) 2017 Published by Elsevier Ireland Ltd.

【 授权许可】

Free