Editors' ChoiceDepression

On antidepressants and still feeling low

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Science Translational Medicine  09 Nov 2016:
Vol. 8, Issue 364, pp. 364ec180
DOI: 10.1126/scitranslmed.aal0068

For some patients, antidepressants are a godsend. However, up to 30% of people on antidepressants do not show the expected favorable response. Because noticeable improvements from antidepressant therapy can take weeks or even months to manifest, markers or events that predict which patients will be responders and which will be nonresponders could speed therapy by preempting the delay before stopping medication and initiating trial of a new type of intervention. Now, Goldstein-Piekarski and collaborators use two factors that previously were independently associated with the development of depression—the presence of a childhood trauma and activation of the amygdala in response to emotional stimuli—to predict, with 80% accuracy, whether an antidepressant will help a patient recover from depression.

It is well known that people who were exposed to early-life stress, such as abuse or neglect, are more prone to suffering from depression later in life. Although the neurobiological mechanism for this association is unknown, a potential explanation is that stress hormones released during early stressful events affect the development and function of a brain structure that plays a seminal role in the processing of emotions: the amygdala. In fact, depressed patients often display abnormal amygdala engagement upon exposure to different emotional stimuli. In the new work, the authors analyzed, by functional magnetic resonance imaging (fMRI), amygdala reactivity to rewarding stimuli (happy faces), adverse stimuli (fearful faces), or both in 70 individuals before and after an 8-week trial with three commonly used antidepressants: sertraline, escitalopram, and venlafaxine. They then correlated the fMRI data with early-life stress history in an attempt to predict improvement in depression symptoms. The correlated data suggested associations between a positive response to antidepressants and either low early-life stress exposure and amygdala hyporeactivity to both, rewarding and adverse cues or high early-life stress exposure and amygdala reactivity to rewarding cues. A routine fMRI scan for all patients with depression is unlikely. But identifying which patients might benefit the most from a drug—perhaps beginning with those who experienced high early-life stress—might save valuable months of nonresponse treatment for people with depression, which can be a life-threatening condition.

A. N. Goldstein-Piekarski et al., Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants. Proc. Natl. Acad. Sci. U.S.A. 113, 11955–11960 (2016). [Full Text]

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