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September 10, 2003

Neurochemical Aspects of Susceptibility to Depression

JAMA. 2003;290(10):1315-1316. doi:10.1001/jama.290.10.1315

In Reply: Dr Nathan suggests that our findings may be related to decreased dopaminergic function, in addition to decreased noradrenergic function. AMPT is a nonspecific inhibitor of catecholamine synthesis, and I agree that decreased dopaminergic function could contribute to the findings. I also agree that it would be of interest to examine nonspecific depletion of monoamines in conjunction with PET imaging of the brain.

Nathan also mentions sex differences in emotional processing and other outcomes relevant to depression. Indeed, a recent meta-analysis found that female sex was an important determinant of risk of tryptophan depletion–induced return of depressive symptoms, as well as history of recurrent depression, prior serotonin reuptake treatment, prior suicidal ideation and attempts, and chronicity of illness.1 In our study, however, we found no differences in brain metabolic response based on sex, although the small sample size may have limited our ability to detect such an effect.

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