Risks For Major Depression: Searching For Stable Traits

Weissman, Myrna M.; Talati, Ardesheer; Hao, Xuejun; Posner, Jonathan

In this issue of Biological Psychiatry, Scifo et al. follow a reasonable clinical and epidemiologic classification to separate biological traits and states. They base their hypothesis on existing strong findings that patients often have lifelong recurring episodes of major depression of increasing severity, shorter remission periods, and reduced therapeutic response. Based on these observations, they reason that patients with differing clinical courses (single episodes, single episodes in remission, recurrent episodes, recurrent episodes in remission, and control subjects) should show differing biological traits and states.

Applying mass spectrometry–based proteomics to postmortem tissue, they tested 3630 proteins within the subgenual anterior cingulate cortex, a region previously implicated in the modulation of negative mood and found to be responsive to deep brain stimulation in patients with treatment-refractory depression. They identified 98 proteins whose expression was associated with major depressive disorder (MDD). Much to their surprise, they found weak evidence of proteomic differences as a function of depressive state. Instead, they found persistent effects of MDD independent of episode or remission, demographic characteristics, or other clinical measures of severity. They concluded that these proteomic differences did not predict state differences, but may have predicted traits. These depression effects were detected in a host of proteomic measures that certainly will guide numerous other investigations.


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February 1, 2022