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

Natalie L Truby; Corinne Smith; Peter J Hamilton

doi:10.1016/j.jad.2025.120198

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

Natalie L Truby·Corinne Smith·Peter J Hamilton

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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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Humans Major Depressive Disorder Brain DNA Transposable Elements Male Female Adult Middle Aged Sequence Analysis, RNA KRAB zinc finger protein (KZFP)Major depressive disorder Transcription factor Transposable element Journal Article

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Natalie L Truby, Corinne Smith, Peter J Hamilton. 2025-09-03. Transposable elements are dysregulated in brains of individuals with major depressive disorder.. https://doi.org/10.1016/j.jad.2025.120198

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