Dataset Information

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report.

ABSTRACT:

Objectives

Previous studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response.

Methods

Individuals in a major depressive episode received escitalopram treatment (10-20 mg/d) for 8 weeks. Depression severity was assessed at baseline and at weeks 8 and 16 using the Montgomery-Asberg Depression Rating Scale (MADRS). Response to treatment was characterized by a significant reduction in the MADRS (≥50%). Nonresponders received adjunctive aripiprazole treatment (2-10 mg/d) for a further 8 weeks. The brain-predicted age difference (brain-PAD) at baseline was determined using machine learning methods trained on 3377 healthy individuals from seven publicly available datasets. The model used features from all brain regions extracted from structural magnetic resonance imaging data.

Results

Brain-PAD was significantly higher in older MDD participants compared to younger MDD participants [t(147.35) = -2.35, p < 0.03]. BMI was significantly associated with brain-PAD in the MDD group [r(155) = 0.19, p < 0.03]. Response to treatment was not significantly associated with brain-PAD.

Conclusion

We found an elevated brain age gap in older individuals with MDD. Brain-PAD was not associated with overall treatment response to escitalopram monotherapy or escitalopram plus adjunctive aripiprazole.

SUBMITTER: Ballester PL

PROVIDER: S-EPMC8556529 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report.

Ballester Pedro L PL Suh Jee Su JS Nogovitsyn Nikita N Hassel Stefanie S Strother Stephen C SC Arnott Stephen R SR Minuzzi Luciano L Sassi Roberto B RB Lam Raymond W RW Milev Roumen R Müller Daniel J DJ Taylor Valerie H VH Kennedy Sidney H SH Frey Benicio N BN

NeuroImage. Clinical 20211023

<h4>Objectives</h4>Previous studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response.<h4>Methods</h4>Individuals in a major depressive episode received escitalopram treatment (10-20 mg/d) for 8 weeks. Depression severity was assessed at baseline and at weeks 8 and 16 using t ...[more]

PMID: 34710675

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Project description:BackgroundMajor 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.MethodsBrain 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).ResultsMean ± 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.ConclusionsBrain age is a reliable and potentially clinically useful biomarker that can prognosticate antidepressant treatment outcomes.

Project description:ObjectiveMajor depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue.MethodDNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate epigenetic aging. Major depression diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying epigenetic aging in blood and brain.ResultsSignificantly higher epigenetic aging was observed in patients with major depression compared with control subjects (Cohen's d=0.18), with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, epigenetic aging was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent data set of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes.ConclusionsAs compared with control subjects, patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.

Dataset Information

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report.

Objectives

Methods

Results

Conclusion

Publications

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report.

Similar Datasets

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