Transposable Elements are Dysregulated in Brains of Individuals with Major Depressive Disorder

Transposable elements (TEs) are repetitive DNA sequences capable of being transcribed and reintegrated, 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 and uniform downregulation of TE transcript expression in the brains of subjects with MDD relative to controls, this occurs most prominently in the orbitofrontal cortex (OFC) brain region, and MDD differentially impacts this TE expression by age and sex. This work points to the aberrant transcription of cortical TEs as a potentially overlooked molecular signature of MDD.