Leo Sher, M.D.

Fifteen years ago, our paper, “Lower CSF homovanillic acid levels in depressed patients with a history of alcoholism” was published in 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.

Sixty-three patients with a current major depressive episode (MDE) and a history of alcoholism, 72 subjects with a current MDE but without a history of alcoholism, and 22 healthy volunteers were included in the study. 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.

The depressed groups had comparable Hamilton Depression Rating Scale and Beck Depression Inventory scores but higher than controls. 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 that suggest 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;28(9):1712-9.