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

BACKGROUND: Sexual minority youth (SMY) are 3 times 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. METHODS: A total of 81 participants ages 15 to 22 years (41% SMY, 52% marginalized race) reported sexual orientation victimization, depression severity, and anhedonia severity, and underwent a monetary reward functional magnetic resonance imaging task. Significant activation to reward > neutral outcome (pfamilywise error < .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. RESULTS: SMY reported higher depression (p < .001), anhedonia (p = .03), and orientation victimization (p < .001) than heterosexual youth. The 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 = .03), with higher depression severity observed in those with a combination of higher mPFC activation and greater orientation victimization. CONCLUSIONS: 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 are a first step toward a clinical neuroscience understanding of minority stress in SMY.

An examination of maternal prenatal BMI and human fetal brain development.

BACKGROUND: Prenatal development is a time when the brain is acutely vulnerable to insult and alteration by environmental factors (e.g., toxins, maternal health). One important risk factor is maternal obesity (Body Mass Index > 30). Recent research indicates that high maternal BMI during pregnancy is associated with increased risk for numerous physical health, cognitive, and mental health problems in offspring across the lifespan. It is possible that heightened maternal prenatal BMI influences the developing brain even before birth. METHODS: The present study examines this possibility at the level of macrocircuitry in the human fetal brain. Using a data-driven strategy for parcellating the brain into subnetworks, we test whether MRI functional connectivity within or between fetal neural subnetworks varies with maternal prenatal BMI in 109 fetuses between the ages of 26 and 39weeks. RESULTS: We discovered that strength of connectivity between two subnetworks, left anterior insula/inferior frontal gyrus (aIN/IFG) and bilateral prefrontal cortex (PFC), varied with maternal BMI. At the level of individual aIN/IFG-PFC connections, we observed both increased and decreased between-network connectivity with a tendency for increased within-hemisphere connectivity and reduced cross-hemisphere connectivity in higher BMI pregnancies. Maternal BMI was not associated with global differences in network topography based on network-based statistical analyses. CONCLUSIONS: Overall effects were localized in regions that will later support behavioral regulation and integrative processes, regions commonly associated with obesity-related deficits. By establishing onset in neural differences prior to birth, this study supports a model in which maternal BMI-related risk is associated with fetal connectome-level brain organization with implications for offspring long-term cognitive development and mental health.