Neuroactive steroid biomarkers of alcohol sensitivity and alcoholism risk

Neuroactive steroids are endogenous modulators of neuronal excitability. The GABAergic neuroactive steroids contribute to regulation of synaptic and extrasynaptic inhibitory transmission across brain, hypothalamic-pituitary-adrenal (HPA) axis function, as well as inflammatory processes and myelin formation. These actions are being translated to new treatments for neurologic and psychiatric conditions. Recent data in animal models suggests a potential therapeutic role for neuroactive steroids in the treatment of alcoholism, depression and premenstrual dysphoric disorders. In addition, neuroactive steroid responses to physiological and/or pharmacological challenge may represent useful biomarkers of alcoholism risk. In particular, the lack of dexamethasone suppression of plasma deoxycorticosterone in ethanol-naïve monkeys predicts the subsequent development of heavy voluntary alcohol consumption. These studies point to the opportunity for biomarker development related to heavy drinking and possibly alcoholism risk. In addition, neuroactive steroid responses to activation of the HPA axis may predict ethanol sensitivity and this factor has been shown to predict alcoholism risk in sons and daughters of alcoholics. Hence, neuroactive steroid responses to pharmacological challenges have potential utility as biomarkers of alcoholism risk.