TY - JOUR
T1 - Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder
AU - Murrough, James W.
AU - Henry, Shannan
AU - Hu, Jian
AU - Gallezot, Jean Dominique
AU - Planeta-Wilson, Beata
AU - Neumaier, John F.
AU - Neumeister, Alexander
N1 - Funding Information:
Conflict of interest Dr. Neumaier reports lecture fees from Eli Lilly and Wyeth, and Dr. Neumeister grant support from Pfizer Inc., Eli Lilly, UCB Pharma Inc., and Ortho-McNeil Janssen Scientific Affairs, LLC.; Dr. Neumeister has grant support from Pfizer Inc., Eli Lilly, UCB Pharma Inc., and Ortho-McNeil Janssen Scientific Affairs, LLC. No other potential conflict of interest relevant to this article was reported. The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding agencies.
Funding Information:
Acknowledgments This study was supported by the National Institute of Mental Health grant R21 MH081103 (ARRA) and grant R21 MH085627, and the VA National Center for Posttraumatic Stress Disorder at the West Haven VA Connecticut Clinical Neurosciences Division.
PY - 2011/2
Y1 - 2011/2
N2 - 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-HT1B receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT1B 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-HT1B 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-HT1B receptor radioligand [11C]P943. Results: Within the VS/VP region of interest, [11C]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-HT1B receptors in humans with MDD. Abnormal 5-HT1B 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-HT1B receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT1B agonists as a novel class of antidepressants.
AB - 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-HT1B receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT1B 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-HT1B 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-HT1B receptor radioligand [11C]P943. Results: Within the VS/VP region of interest, [11C]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-HT1B receptors in humans with MDD. Abnormal 5-HT1B 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-HT1B receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT1B agonists as a novel class of antidepressants.
KW - Brain imaging
KW - Human subjects
KW - Major depressive disorder
KW - Positron emission tomography
KW - Serotonin
KW - Serotonin1B receptor
KW - Ventral striatum
UR - http://www.scopus.com/inward/record.url?scp=79952489723&partnerID=8YFLogxK
U2 - 10.1007/s00213-010-1881-0
DO - 10.1007/s00213-010-1881-0
M3 - Article
C2 - 20480149
AN - SCOPUS:79952489723
SN - 0033-3158
VL - 213
SP - 547
EP - 553
JO - Psychopharmacology
JF - Psychopharmacology
IS - 2-3
ER -