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

Kristen L. Eckstrand, Jennifer S. Silk, Melissa Nance, Meredith L. Wallace, Nicole Buckley, Morgan Lindenmuth, Luis Flores, Gabriela Alarcón, Karina Quevedo, Mary L. Phillips, Carly J. Lenniger, M. McLean Sammon, Alyssa Brostowin, Neal Ryan, Neil Jones, Erika E. Forbes

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 (p familywise 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.

Original languageEnglish (US)
Pages (from-to)1289-1297
Number of pages9
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number12
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by the National Institute of Mental Health (Grant Nos. R01MH104418 and R01MH104418-02S1 to EEF [Principal Investigator]). KLE completed this research with postdoctoral funding from the National Institute of Mental Health (Grant No. T32 MH018269 ).

Publisher Copyright:
© 2022 Society of Biological Psychiatry


  • Adolescence
  • Depression
  • Medial prefrontal cortex
  • Reward
  • Sexual minority youth
  • Victimization
  • Sexual Behavior
  • Humans
  • Male
  • Prefrontal Cortex
  • Young Adult
  • Adolescent
  • Female
  • Adult

PubMed: MeSH publication types

  • Journal Article


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