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Letters to the Editor
October 6, 2008

Assessing the Assessment of Brain Serotonin Turnover—Reply

Arch Gen Psychiatry. 2008;65(10):1223-1224. doi:10.1001/archpsyc.65.10.1223-b

In reply

Dr Anderson's critique rests heavily on his a priori assumption that the variability in serotonin turnover that we describe is inconsistent with the underlying physiological process examined. Such a view is not consistent with the observations that brain serotonin is involved in an array of physiological processes and may be influenced by, among other things, season,1-3 bright light,3,4 and adiposity.5 Otte and colleagues6 recently documented an association between carriage of the s allele of the serotonin transporter, depression, perceived stress, elevated urinary norepinephrine levels, and, by inference, sympathetic nervous activation. Using direct cardiac catheterization techniques coupled with state-of-the-art norepinephrine isotope dilution methods, we have recently demonstrated that sympathetic activity in unmedicated patients with depression follows a bimodal distribution, with values in some patients being extraordinarily high and others being marginally lower than those found in healthy subjects.7 Indeed, variability in biochemical measures has both hampered and characterized the search for biochemical markers of major depressive disorder.

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