Medial Prefrontal Cortex Activity to Reward Outcome Moderates the Association Between Victimization Due to Sexual Orientation and Depression in Youth

Sexual minority youth (SMY) are 3x more likely to experience depression than heterosexual peers. Minority stress theory posits that this association is explained by sexual orientation victimization, which acts as a stressor to impact depression. For those vulnerable to the effects of stress, victimization may worsen depression by altering activity in neural reward systems. This study examines whether neural reward systems moderate the influence of sexual orientation victimization, a common and distressing experience in SMY, on depression. 81 participants ages 15-22yrs (41% SMY, 52% marginalized race) reported sexual orientation victimization, depression severity, anhedonia severity, and underwent a monetary reward fMRI task. Significant activation to reward>neutral outcome( p FWE <0.05) was determined within a meta-analytically derived Neurosynth “reward” mask. A univariate linear model examined the impact of reward activation and identity on victimization-depression relationships. SMY reported higher depression ( p <0.001), anhedonia( p= 0.03), and orientation victimization( p <0.001) than heterosexual youth. Bilateral ventral striatum, medial prefrontal cortex (mPFC), anterior cingulate cortex, and right orbitofrontal cortex were significantly active to reward. mPFC activation moderated associations between sexual orientation victimization and depression( p =0.03), with higher depression severity observed in those with a combination of higher mPFC activation and greater orientation victimization. Sexual orientation victimization was related to depression, but only in the context of higher mPFC activation, a pattern observed in depressed youth. These novel results provide evidence for neural reward sensitivity as a vulnerability factor for depression in SMY, suggesting mechanisms for disparities, and is a first step towards a clinical neuroscience of minority stress in SMY.