78. Targeted rejection life events trigger altered glucocorticoid receptor mRNA expression and major depressive disorder in adolescents

Abstract

Although life stress has been implicated in the pathogenesis of depression, the biological processes that underlie this effect remain unclear. We addressed this issue by examining whether a particularly noxious type of psychological stress, targeted rejection, alters neuroimmunologic signaling in a way that increases risk for major depressive disorder (MDD). One hundred and forty-seven adolescent women at elevated risk for depression were evaluated every six months for 2.5 years. At each visit, participants were administered semi-structured interviews that assessed for the presence of recent life stress (i.e., the UCLA Life Stress Interview) and current MDD (i.e., the SCID-I). Participants also had blood drawn at each visit to quantify leukocyte mRNA for the glucocorticoid receptor, GR-alpha. Hierarchical linear modeling analyses revealed that, when controlling for age, ethnicity, and alcohol consumption, participants had more mRNA for GR-alpha at visits when they had experienced a recent targeted rejection life event compared to visits when no recent targeted rejection life event had occurred (b = .88, p = .02). Additional analyses revealed that more mRNA for GR-alpha predicted a greater likelihood of MDD at the subsequent visit (b = .12, p = .005). To our knowledge, these data are the first to show that exposure to an acute social rejection life event predicts altered glucocorticoid receptor mRNA expression in a way that increases a person’s subsequent risk for MDD.