Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex

Abstract

While a definitive understanding of the molecular pathology of posttraumatic stress disorder (PTSD) is far from a current reality, it has become increasingly clear that many of the molecular effects of PTSD are sex specific. Women are twice as likely as men to develop PTSD after a traumatic event, and neurobiological evidence suggests that there are structural differences between the brains of males versus females with PTSD. Recent advances in genomic technologies have begun to shed light on the sex-specific molecular determinants of PTSD, which seem to be governed predominantly by dysfunction of GABAergic (gamma-aminobutyric acidergic) signaling and immune function. We review the current state of the field of PTSD genomics focusing on the effect of sex. We provide an overview of difference in heritability of PTSD based on sex, how difference in gene regulation based on sex impacts the PTSD brain, and what is known about genomic regulation that is dysregulated in specific cell types in PTSD.