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Letters to the Editor
October 6, 2008

Assessing the Assessment of Brain Serotonin Turnover

Arch Gen Psychiatry. 2008;65(10):1223. doi:10.1001/archpsyc.65.10.1223-a

I would like to comment on several critical aspects of the January 2008 article of Barton and colleagues1 entitled “Elevated Brain Serotonin Turnover in Patients With Depression: Effect of Genotype and Therapy.”

The authors indicate that measured internal jugular venoarterial (VA) differences in plasma levels of 5-hydroxyindoleacetic acid (5-HIAA, the major serotonin metabolite) are proportionally related to brain serotonin turnover. It is difficult to reconcile this view with the fact that observed individual VA differences were often quite close to or less than zero. Thus, the standard deviations observed for baseline VA gradients in both the major depressive disorder and control groups were similar to or greater than the means, and 6 of 11 patients with major depressive disorder appeared to have no VA gradient after selective serotonin reuptake inhibitor (SSRI) treatment. It seems inconceivable that a substantial fraction of subjects has little or no brain serotonin turnover and that others have many-fold higher rates of turnover. Even putting aside those subjects with zero or negative VA differences, there is a tremendous interindividual range that is inconsistent with the underlying physiological process that is purportedly indexed.

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