Effects of sex and gender on the etiologies and presentation of select internalizing psychopathologies

Abstract

Abstract The internalizing spectrum encompasses a subset of psychopathologies characterized by emotional liability, anhedonia, anxiousness, distress, and fear, and includes, among others, diagnoses of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD). In this review, we describe the vast body of work highlighting a role for sex and gender in the environment, symptom onset, genetic liability, and disorder progression and comorbidities of MDD, GAD, and PTSD. We also point the reader to different language used in diverse fields to describe sexual and gender minorities that may complicate the interpretation of emerging literature from the social sciences, psychiatric and psychological sciences, and genetics. Finally, we identify several gaps in knowledge that we hope serve as launch-points for expanding the scope of psychiatric studies beyond binarized sex-stratification. Despite being under-represented in genomics studies, placing emphasis on inclusion of sexual and gender diverse participants in these works will hopefully improve our understanding of disorder etiology using genetics as one tool to inform how biology (e.g., hormone concentration) and environmental variables (e.g., exposure to traumatic events) contribute to differences in symptom onset, pattern, and long-term trajectory.