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

Abstract

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 Δ 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 Δ 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 Δ 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 antidepressant treatment outcomes.

• Authors: Manish K Jha, Cherise Chin Fatt, Abu Minhajuddin, Taryn L Mayes, Madhukar H Trivedi
• Journal: Biological psychiatry. Cognitive neuroscience and neuroimaging (Biol Psychiatry Cogn Neurosci Neuroimaging) Vol. 8 Issue 4 Pg. 462-470 (04 2023) ISSN: 2451-9030 [Electronic] United States
• PMID: 36179972 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antidepressive Agents
• Biomarkers
• Embarc
• Sertraline

Topics

• Adult
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Aging
• Antidepressive Agents (therapeutic use)
• Biomarkers
• Brain (diagnostic imaging)
• Depressive Disorder, Major (diagnosis)
• Reproducibility of Results
• Sertraline (therapeutic use)