Leo Sher, M.D.

Our research paper, “Lower CSF homovanillic acid levels in depressed patients with a history of alcoholism” was published 20 years ago, in the September 2003 issue of Neuropsychopharmacology (1). We compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in depressed subjects with or without a history of alcoholism and healthy volunteers. We hypothesized that depressed subjects with a history of alcoholism would be more aggressive, impulsive, and suicidal than depressed subjects without a history of alcoholism and would have lower CSF monoamine metabolite levels.

Depressive symptoms, lifetime aggression, impulsivity, Axis II disorders, and suicidal behavior were assessed. CSF was sampled and homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-performance lipid chromatography with electrochemical detection.

Depressed subjects with a history of alcoholism had lower CSF HVA levels, and higher lifetime aggression and current suicide ideation scale scores and were more likely to be tobacco smokers compared with depressed subjects without a history of alcoholism. Low HVA was present after adjustment for sex, aggression and depression scores, cigarette smoking, antisocial and borderline personality disorders, psychomotor retardation, and delusions. Controls had CSF HVA levels intermediate between the two patient groups. We found no group difference in CSF 5-HIAA and MHPG levels.

Low CSF HVA suggests that impaired dopaminergic activity is associated with a history of alcoholism in persons with current MDE. Our finding is consistent with studies suggesting that dopaminergic mechanisms play a part in the pathophysiology of alcohol use disorders, including mechanisms of alcohol dependence and withdrawal.

Reference

1. Sher L, Oquendo MA, Li S, Huang YY, Grunebaum MF, Burke AK, Malone KM, Mann JJ. Lower CSF homovanillic acid levels in depressed patients with a history of alcoholism. Neuropsychopharmacology. 2003 Sep;28(9):1712-9. doi: 10.1038/sj.npp.1300231. Epub 2003 Jun 25.