Patients With Depression Exhibit High Serotonin Turnover Rates

Discovering the biological basis of major depressive disorder (MDD) could lead to improved medication and therapeutic treatment for patients with this condition. To date, the cause of MDD is not well understood, but researchers believe that elevated levels of the brain serotonin, 5-hydroxytryptamine (5-HT), may play a role. Dr David A. Barton and colleagues recently researched the role of 5-HT turnover in MDD. The results were published in the January issue of Archives of General Psychiatry.

A total of 21 patients who met the criteria for MDD according to DSM-IV and International Statistical Classification of Diseases standards and 40 healthy volunteers were included in the study. Patients with MDD had not been receiving treatment with antidepressants or benzodiazepines for at least 4 weeks before the study. At study start, 11 patients with MDD received treatment with an SSRI and 10 patients with MDD received no treatment. Repeated blood samples from the internal jugular vein were taken at baseline and after approximately 12 weeks from all participants. The samples were then analyzed using 5-hydroxyindoleacetic acid (5-HIAA) plasma concentrations to determine 5-HT turnover rates.

Arterial 5-HIAA plasma concentration remained the same in patients with MDD (mean, 46 nmol/L) and in controls (mean, 42 nmol/L); however, the internal jugular venoarterial 5-HIAA plasma concentration gradient was significantly elevated in nonmedicated patients with MDD compared with controls (mean, 4.4 vs 1.6 nmol/L, respectively), which indicates elevated 5-HT turnover. No difference in results between the sexes was reported in patients with MDD (mean, 4.2 nmol/L for women; 4.6 nmol/L for men), and there was no quantitative link to the assessed risk of suicide. In the 11 patients with MDD treated with an SSRI, 5-HT turnover was substantially reduced following medication therapy (mean, 6.0 nmol/L pretreatment vs 2.0 nmol/L posttreatment). Further analysis of the influence of the 5-HT transporter genotype in MDD indicated that patients who carried the s allele compared with the l allele were associated with a greater than 2-fold increase in 5-HT turnover. Because 3 of 4 patients who smoked and who had MDD carried the s allele, it was found that smokers had a greater 5-HT turnover than nonsmokers.

The authors recognized several confounders of their results and concluded: "Whether elevated brain serotonin turnover occurs as a result of increased neuronal activity or enhanced vesicular leakage and subsequent intraneuronal metabolism remains." -unknown