A Transcriptomic Signature of Depressive Symptoms in Late Life

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Late-life depressive symptoms are linked to impaired daily function and cognitive decline.
• The underlying molecular brain mechanisms remain poorly understood.

Purpose of the Study:

• To investigate the transcriptomic correlates of depressive symptoms in late life.
• To identify potential molecular markers and sex-specific differences in the aging brain.

Main Methods:

• Differential gene expression analysis of dorsolateral prefrontal cortex RNA sequencing data from 998 elderly participants (ROS/MAP study).
• Analysis correlated gene expression with pre-mortem depressive symptoms, controlling for Alzheimer's disease, medications, and lifestyle factors.
• Sex-stratified analyses were performed.

Main Results:

• Increased abundance of PWAR1 and CTDSPL2 genes associated with higher depressive symptom burden.
• Functional analysis indicated altered aerobic metabolism, amino acid catabolism, and DNA modification.
• Gene expression patterns showed poor correlation between sexes, with significant findings primarily in males.

Conclusions:

• PWAR1 and CTDSPL2 are identified as potential markers for late-life depression in the prefrontal cortex.
• The study reveals novel insights into sex-specific molecular regulators of depression in aging.
• Findings suggest distinct transcriptomic signatures for depression in males and females in late life.