Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations.
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.
Heinz
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A
National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA. heinza@as200.zi-mannheim.de
Weingartner
H
H
George
D
D
Hommer
D
D
Wolkowitz
O M
OM
Linnoila
M
M
D000328:Adult; D016022:Case-Control Studies; D003687:Dehydroepiandrosterone / Q000378:metabolism; D003863:Depression / Q000097:blood / Q000134:cerebrospinal fluid / Q000139:chemically induced* / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications* / Q000378:metabolism*
D018377:Neurotransmitter Agents; D000431:Ethanol; D003687:Dehydroepiandrosterone; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006854:Hydrocortisone; D006719:Homovanillic Acid