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Reward-Related Brain Function as an Endophenotype in the Mood-Psychosis Spectrum.

Marjolein E A Barendse1, Robert M Bilder2, Anne L Snijders1,3

  • 1Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.

Biological Psychiatry Global Open Science
|April 17, 2026
PubMed
Summary
This summary is machine-generated.

Ventral striatum (VS) activation during reward anticipation did not differ between patients with psychotic/bipolar disorders, their relatives, and controls. This suggests VS activation is not an endophenotype for these conditions.

Keywords:
BipolarFamilial riskPolygenic riskPsychosisRewardfMRI

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • The striatal reward system's function is linked to psychotic and bipolar disorders.
  • This study investigated ventral striatum (VS) activation during reward anticipation as a potential endophenotype for these disorders.
  • Hypotheses included lower VS activation in patients, intermediate in relatives, and associations with polygenic risk scores (PRSs) and symptoms.

Purpose of the Study:

  • To determine if ventral striatum (VS) activation during reward anticipation meets endophenotype criteria for psychotic and bipolar disorders.
  • To examine group differences in VS activation among patients, relatives, and controls.
  • To explore relationships between VS activation, symptom severity, and genetic risk.

Main Methods:

  • 127 patients, 66 controls, and 51 relatives underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay task.
  • Diagnoses were clinically confirmed, and PRSs for schizophrenia, bipolar disorder, and major depressive disorder were calculated.
  • Linear mixed effects models analyzed group differences, symptom effects, and PRS associations with VS activation.

Main Results:

  • No significant differences in VS activation during reward anticipation were found between patients, relatives, and control groups.
  • Current symptom levels and PRSs were not significantly associated with VS activation.
  • These findings remained consistent after controlling for substance and medication use.

Conclusions:

  • Ventral striatum (VS) activation during reward anticipation does not appear to meet the criteria for an endophenotype of bipolar and psychotic disorders.
  • Further research is recommended to explore neural activation associations with symptom levels across diagnostic boundaries in more symptomatic populations.