Major depressive disorder (MDD) is a highly disabling, heterogeneous illness that affects nearly 15 million American adults in a given year. One of the many goals in the study of pathophysiology of MDD is to identify and characterize candidate biological signatures (ie, biomarkers) for this common neuropsychiatric condition. Importantly, ample evidence indicates that the prevalence of MDD among females is roughly twice that of males, and therefore, studies that examine the putative sex-specific neurobiological mechanisms underlying MDD are warranted.
It’s well established in the literature that individuals suffering from depression present with dysfunction in the neural circuitry of physiological stress response, and emotion processing and regulation. New findings published in the journal Psychophysiology indicate that the neurophysiological reactivity to negative stimuli, as measured by pupillary dilation, has a potential to serve as a reliable, easy-to-measure marker of risk for recurrence of depression in adult women.
Investigators administered the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Beck Depression Inventory-II (BDI-II) to 57 women with a past history of MDD at five different time points during a 24-month period. They assessed current symptoms of depression, new episodes of depression, as well as rates of depression recurrence. Thirty-eight participants completed the fifth, and final, follow-up assessment.
Peak pupil size (ie, dilation) was assessed during the task that involved the presentation of various stimuli [ie, full-color images of actors displaying positive (eg, happy), negative (eg, angry, sad), or neutral emotions]. Participants were asked to indicate which emotion was being presented by pressing a corresponding button. Depressive symptoms and symptoms of anxiety at baseline were included as covariates in the analysis of peak pupillary response to stimuli during a 2-year follow-up.
Results indicate that women who showed decreased peak pupil dilation when negative emotion (eg, sad face) was displayed on the screen presented with recurring symptoms of depression sooner during the 2-year-long study, compared with that of women who showed moderate or increased peak pupil dilation. With regard to the peak pupil dilation when a different negative emotion (eg, angry face) was displayed on the screen, women who showed either increased or decreased peak pupil dilation were at greater risk for depression recurrence, compared with that of women who showed moderate peak pupil dilation. In line with previously reported findings, peak pupil dilation was not a significant predictor of depression recurrence when participants were shown stimuli depicting positive (eg, happy face) emotions.
“However, when quadratic effects of peak pupil dilation to all three emotions [(ie, sad, angry, happy)] were included in the analysis, the quadratic effect of peak pupil dilation to angry faces was the only significant predictor of time to depression recurrence, but not the quadratic effects of peak pupil dilation to happy or sad faces,” investigators wrote in their publication. Nearly 50% of women who showed decreased peak pupil dilation to angry faces (lowest tertile), and more than 35% of women who showed increased peak pupil dilation to angry faces (highest tertile), presented with recurring symptoms of depression during 24 months, compared with that of 15% of women who showed moderate peak pupil dilation to angry faces (middle tertile).
These data indicate that, “if replicated, pupillary reactivity could be used as a biomarker to determine which at-risk individuals are at greatest risk for recurrence so that limited intervention resources could be targeted to those most at need,” the authors concluded.
Kudinova AY, Burkhouse KL, Siegle G, et al. Pupillary reactivity to negative stimuli prospectively predicts recurrence of major depressive disorder in women. Psychophysiology. 2016. doi: 10.1111/psyp.12764. [Epub ahead of print]