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September 10, 2025Open Access

Transposable elements are dysregulated in brains of individuals with major depressive disorder

NTNatalie L. TrubyVirginia Commonwealth University CSC. SmithBoston University PHPeter J. HamiltonAllen Institute for Brain Science

Key Points

Dysregulation of transposable elements is highlighted in individuals with major depressive disorder, showing notable expression differences.
TE transcript expression significantly differs between individuals with major depressive disorder and healthy controls in brain tissue samples.
This study employs RNA sequencing to analyze TE transcripts in postmortem human brain, revealing possible mechanisms in MDD.
Findings indicate that the aberrant transcription of cortical TEs may serve as an important molecular signature for major depressive disorder.

Abstract

Transposable elements (TEs) are repetitive DNA sequences capable of being transcribed and re-integrated, or transposed, into distinct loci throughout the genome. While thought to be largely transcriptionally silenced in brain, TE transcription is increasingly recognized as dynamic and involved in human health and disease states, including in disorders of the brain. In this study, we annotated TE transcripts in publicly available RNA sequencing (RNAseq) of postmortem human brain tissue to investigate the expression profile of TE transcripts in individuals with major depressive disorder (MDD) compared to healthy controls. Our findings reveal a robust impact to TE transcript expression in the brains of subjects with MDD relative to controls. This work points to the aberrant transcription of cortical TEs as a potentially overlooked molecular signature of MDD.

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