Accelerated Brain Aging in Adults With Major Depressive Disorder Predicts Poorer Outcome With Sertraline: Findings From the EMBARC Study

BACKGROUND: Major depressive disorder (MDD) may be associated with accelerated brain aging (higher brain age than chronological age). This report evaluated whether brain age is a clinically useful biomarker by checking its test -retest reliability using magnetic resonance imaging scans acquired 1 week apart and by evaluating the association of accelerated brain aging with symptom severity and antidepressant treatment outcomes.METHODS: Brain age was estimated in participants of the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study using T1-weighted structural magnetic resonance imaging (MDD n = 290; female n = 192; healthy control participants n = 39; female n = 24). Intraclass correlation coefficient was used for baseline-to-week-1 test-retest reliability. Association of baseline D brain age (brain age minus chronological age) with Hamilton Depression Rating Scale-17 and Concise Health Risk Tracking Self-Report domains (impulsivity, suicide propensity [measures: pessimism, helplessness, perceived lack of social support, and despair], and suicidal thoughts) were assessed at baseline (linear regression) and during 8-week-long treatment with either sertraline or placebo (repeated-measures mixed models).RESULTS: Mean +/- SD baseline chronological age, brain age, and D brain age were 37.1 +/- 13.3, 40.6 +/- 13.1, and 3.1 +/- 6.1 years in MDD and 37.1 +/- 14.7, 38.4 +/- 12.9, and 0.6 +/- 5.5 years in healthy control groups, respectively. Test-retest reliability was high (intraclass correlation coefficient = 0.98-1.00). Higher baseline D brain age in the MDD group was associated with higher baseline impulsivity and suicide propensity and predicted smaller baseline-to-week-8 reductions in Hamilton Depression Rating Scale-17, impulsivity, and suicide propensity with sertraline but not with placebo.CONCLUSIONS: Brain age is a reliable and potentially clinically useful biomarker that can prognosticate antide-pressant treatment outcomes.

Automated summary

This study evaluated the association between major depressive disorder (MDD) and accelerated brain aging, and found that brain age can serve as a clinically useful biomarker. The results showed that brain age is associated with the severity of depressive symptoms and antidepressant treatment outcomes.