Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations

Abstract

Depressed mood increases the relapse risk of abstinent alcoholics; its neurobiological correlates may include reduced serotonin and norepinephrine turnover rates and increased cortisol concentrations during detoxification stress. Neurosteroids such as dehydroepiandrosterone and its sulfate (DHEA and DHEA-S) may antagonize cortisol action and may have mood-elevating effects on their own. We measured severity of depression with Beck’s Depression Inventory (BDI) and Hamilton’s Depression Rating Scale (HDRS), plasma concentrations of cortisol, DHEA and DHEA-S, and CSF concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and the dopamine metabolite homovanillic acid (HVA) in 21 abstinent alcoholics after 4 weeks of abstinence and in 11 age-matched healthy control subjects. Only CSF MHPG concentrations were reduced in alcoholics compared to control subjects (41.4±6.6 vs. 53.3±8.6 pmol/ml). Self-rated depression was significantly correlated with CSF MHPG (Spearman’s R=+0.57, P<0.01), CSF 5-HIAA ( R=+0.51, P<0.05) and plasma cortisol concentrations ( R=+0.50, P<0.05). Negative correlations were found between DHEA-S concentrations and both self-rated depression ( R=−0.45, P<0.05) and observer-rated depression ( R=−0.55, P<0.05). The ratio of DHEA-S to cortisol serum concentrations was also negatively correlated with depression (BDI: R=−0.55, P<0.01; HDRS: R=−0.63, P<0.005). Anxiety (Spielberger’s State Anxiety Scale) was only associated with CSF MHPG concentrations ( R=+0.58, P<0.01). Our findings point to the importance of noradrenergic dysfunction in the pathogenesis of depression among abstinent alcoholics and indicate that their mood states may also be modulated by a low DHEA-S to cortisol ratio, hypothetically indicative of low stress protection capacities.