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


OBJECTIVE
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.
Murrough
James W
JW
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Henry
Shannan
S
Hu
Jian
J
Gallezot
Jean-Dominique
JD
Planeta-Wilson
Beata
B
Neumaier
John F
JF
Neumeister
Alexander
A
D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism; D006801:Humans; D008297:Male; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000379:methods; D011760:Pyrrolidinones; D019275:Radiopharmaceuticals; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D055815:Young Adult
C546827:1-(4-(2-methoxyisopropyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)benzyl)pyrrolidin-2-one; D010879:Piperazines; D011760:Pyrrolidinones; D019275:Radiopharmaceuticals; D044302:Receptor, Serotonin, 5-HT1B; D058829:Serotonin 5-HT1 Receptor Antagonists