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Accelerated brain aging predicts impulsivity and symptom severity in depression.

Katharine Dunlop1,2, Lindsay W Victoria3,4, Jonathan Downar5,6

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Major depressive disorder (MDD) is linked to accelerated brain aging, identified through functional connectivity patterns. This accelerated aging correlates with increased impulsivity and depression severity in patients.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Aging Research

Background:

  • Neuroimaging measures change across the lifespan and can predict chronological age.
  • Accelerated brain aging, a deviation from expected age-based brain metrics, is linked to various health risks.
  • The impact of major depressive disorder (MDD) on age-related functional connectivity changes remains unclear.

Purpose of the Study:

  • To investigate if resting-state functional connectivity shows accelerated brain aging in individuals with MDD.
  • To determine if accelerated brain aging in MDD is associated with specific cognitive deficits.
  • To explore the relationship between accelerated brain aging and clinical outcomes in MDD.

Main Methods:

  • A support vector regression model was trained to predict age from resting-state functional connectivity in 710 healthy adults (aged 18-89).
  • This age prediction model was applied to a sample of 109 actively depressed MDD participants.
  • Brain age was calculated as the difference between predicted brain age and chronological age.

Main Results:

  • MDD patients exhibited a significantly greater predicted brain age compared to control participants (2.11 years older, p=0.015).
  • Accelerated brain aging in MDD was associated with increased impulsivity and, in males, greater depressive severity.
  • Accelerated brain aging also correlated with increased placebo response in a repetitive transcranial magnetic stimulation trial.

Conclusions:

  • Major depressive disorder is associated with accelerated brain aging, as evidenced by resting-state functional connectivity.
  • Accelerated brain aging in MDD selectively predicts greater impulsivity and depression severity.
  • These findings highlight a potential neurobiological marker in MDD and its association with specific clinical features.