The American journal of psychiatryJul 6, 2022

Comparing Gene Activity Patterns in Brain Thinking and Emotion Areas in PTSD and Depression

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 22, 2026

Abstract

A total of 107 donors diagnosed with PTSD and 109 diagnosed with MDD were examined for gene expression differences in the human cortex and amygdala.

A limited number of genes were identified as differentially expressed specifically in PTSD, primarily located in cortical regions.
PTSD-specific genes were associated with downregulated immune-related pathways and microglia, as well as certain types of inhibitory neurons.
A greater number of differentially expressed genes were found in MDD, with most overlapping with those in PTSD and only a few being unique to MDD.
Weighted gene coexpression network analysis confirmed the observed cellular and molecular associations in both disorders.
The findings suggest a potential role of reduced immune signaling and neuroinflammation in the pathophysiology of both MDD and PTSD.

Simplified

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease that is highly comorbid with major depressive disorder (MDD) and bipolar disorder. The overlap in symptoms is hypothesized to stem from partially shared genetics and underlying neurobiological mechanisms. To delineate conservation between transcriptional patterns across PTSD and MDD, the authors examined gene expression in the human cortex and amygdala in these disorders.

METHODS: RNA sequencing was performed in the postmortem brain of two prefrontal cortex regions and two amygdala regions from donors diagnosed with PTSD (N=107) or MDD (N=109) as well as from neurotypical donors (N=109).

RESULTS: The authors identified a limited number of differentially expressed genes (DEGs) specific to PTSD, with nearly all mapping to cortical versus amygdala regions. PTSD-specific DEGs were enriched in gene sets associated with downregulated immune-related pathways and microglia as well as with subpopulations of GABAergic inhibitory neurons. While a greater number of DEGs associated with MDD were identified, most overlapped with PTSD, and only a few were MDD specific. The authors used weighted gene coexpression network analysis as an orthogonal approach to confirm the observed cellular and molecular associations.

CONCLUSIONS: These findings provide supporting evidence for involvement of decreased immune signaling and neuroinflammation in MDD and PTSD pathophysiology, and extend evidence that GABAergic neurons have functional significance in PTSD.

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Competing interests

Disclosures : Andrew E. Jaffe is now employed by Neumora Therapeutics, a for-profit biotechnology company, which is unrelated to the contents of this manuscript. No other authors have financial relationships with commercial interests.

PubMed

Comparing Gene Activity Patterns in Brain Thinking and Emotion Areas in PTSD and Depression

Abstract

Full Text

Funding

Competing interests

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