Impact of the glucocorticoid receptor BclI polymorphism on reward expectancy and prediction error related ventral striatal reactivity in depressed and healthy individuals.
There is evidence that reward-related neural reactivity is altered in depressive disorders. Glucocorticoids influence dopaminergic transmission, which is widely implicated in reward processing. However, no studies have examined the effect of glucocorticoid receptor gene polymorphisms on reward-related neural reactivity in depressed or healthy individuals. Fifty-nine depressed individuals with major depressive disorder (n=33) or bipolar disorder (n=26), and 32 healthy individuals were genotyped for the glucocorticoid receptor BclI G/C polymorphism, and underwent functional magnetic resonance imaging during a monetary reward task. We examined the effect of the glucocorticoid receptor BclI G/C polymorphism on reward expectancy (RE; expected outcome value) and prediction error (PE; discrepancy between expected and actual outcome) related ventral striatal reactivity. There was a significant interaction between reward condition and BclI genotype (p=0.007). C-allele carriers showed higher PE than RE-related right ventral striatal reactivity (p<0.001), whereas no such difference was observed in G/G homozygotes. Accordingly, C-allele carriers showed a greater difference between PE and RE-related right ventral striatal reactivity than G/G homozygotes (p<0.005), and also showed lower RE-related right ventral striatal reactivity than G/G homozygotes (p=0.011). These findings suggest a slowed transfer from PE to RE-related ventral striatal responses during reinforcement learning in C-allele carriers, regardless of diagnosis, possibly due to altered dopamine release associated with increased sensitivity to glucocorticoids.
Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Byung-Joo
BJ
Ham
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA greenbergt@upmc.edu.
Tsafrir
T
Greenberg
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Henry W
HW
Chase
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mary L
ML
Phillips
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000523:psychology*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics / Q000523:psychology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012054:Reinforcement, Psychology; D012201:Reward; D066328:Ventral Striatum / Q000378:metabolism; D055815:Young Adult
D011965:Receptors, Glucocorticoid; D004298:Dopamine
Depression; fMRI; glucocorticoid; polymorphism; reward; striatum