Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder.

RATIONALE

Although serotonin (5-HT) dysregulation is implicated in the pathophysiology of major depressive disorder (MDD), the role of specific receptor subtypes remains to be elucidated. Emerging preclinical research suggests an important role for the 5-HT(1B) receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT(1B) heteroreceptors located within the striatum have been shown to play an essential role in antidepressant action.

OBJECTIVES

The objective of this study was to determine 5-HT(1B) receptor binding potential (BP (ND)) in the region of the ventral striatum/ventral pallidum (VS/VP) in individuals with MDD and healthy control participants.

METHODS

Ten participants with MDD (30.8 ± 9.5 years, five men/five women) in a current major depressive episode (MDE) and ten healthy control participants (30.7 ± 10.5 years, five men/five women) underwent positron emission tomography (PET) scanning with the selective 5-HT(1B) receptor radioligand [(11)C]P943.

RESULTS

Within the VS/VP region of interest, [(11)C]P943 BP (ND) was significantly reduced in the MDD group compared with the healthy control group (1.37 ± 0.13 and 1.68 ± 0.16, respectively; 18.7% between-group difference; p < 0.001).

CONCLUSIONS

Consistent with preclinical and postmortem data, our findings suggest abnormally reduced function of VS/VP 5-HT(1B) receptors in humans with MDD. Abnormal 5-HT(1B) heteroreceptor function may contribute to dysfunctional reward signaling within the striatum, including the nucleus accumbens, via interaction with dopamine, γ-amino-butyric acid, or glutamate systems. Our findings suggest reduced 5-HT(1B) receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT(1B) agonists as a novel class of antidepressants.