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bioRxiv · 10.1101/2025.04.18.649538

Decisional reference point pathology: a mechanism and marker for major depressive disorder in humans

Vittala, A.·Wu, L.·Yan, D.·Liebers, D.·Tell, E.·Song, X.·Dashti, D.·Louie, K.·Raio, C.·Iosifescu, D. V.·Glimcher, P.
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Abstract

The decisional reference point, the central mechanism of behavioral economics, conditions our evaluations of reinforcers. It determines whether a given event is experienced as positive or negative. Here we show, for the first time, a significant and pathological elevation of the reference point in patients with depression that correlates with disease severity. We also show that the mechanism for reference point setting is profoundly impaired in patients with depression. These findings link the previously demonstrated treatment of depression by deep brain stimulation to modulation of the reference point in the anterior cingulate cortex and identify pathology in the dynamics of reference point setting as a novel mechanism in the disorder. Finally, these results lay the foundation for a three-minute virtual diagnostic test for depression.

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Vittala, A., Wu, L., Yan, D., Liebers, D., Tell, E., Song, X., Dashti, D., Louie, K., Raio, C., Iosifescu, D. V., Glimcher, P.. 2025-04-23. Decisional reference point pathology: a mechanism and marker for major depressive disorder in humans. https://doi.org/10.1101/2025.04.18.649538

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