Epigenetic Aging in Major Depressive Disorder.
OBJECTIVE
Major 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.


METHOD
DNAm 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.


RESULTS
Significantly 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.


CONCLUSIONS
As 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.
['Han|Laura K M|LKM|', 'Aghajani|Moji|M|', 'Clark|Shaunna L|SL|', 'Chan|Robin F|RF|', 'Hattab|Mohammad W|MW|', 'Shabalin|Andrey A|AA|', 'Zhao|Min|M|', 'Kumar|Gaurav|G|', 'Xie|Lin Ying|LY|', 'Jansen|Rick|R|', 'Milaneschi|Yuri|Y|', 'Dean|Brian|B|', 'Aberg|Karolina A|KA|', 'van den Oord|Edwin J C G|EJCG|', 'Penninx|Brenda W J H|BWJH|']
D000328:Adult D000069586:Adult Survivors of Child Adverse Events D000375:Aging D001921:Brain D016022:Case-Control Studies D019175:DNA Methylation D003865:Depressive Disorder, Major D005260:Female D006304:Health Status D006801:Humans D008019:Life Style D008137:Longitudinal Studies D008297:Male D009426:Netherlands
Assay Techniques Genetics Mood Disorders-Unipolar