Associations between dopamine D2 receptor availability and BMI depend on age

The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects' ages despite the large impact of age on DRD2/3 l...

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Bibliographic Details
Published in:NeuroImage (Orlando, Fla.) Fla.), 2016-09, Vol.138, p.176-183
Main Authors: Dang, Linh C., Samanez-Larkin, Gregory R., Castrellon, Jaime J., Perkins, Scott F., Cowan, Ronald L., Zald, David H.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age
Aged
Aged, 80 and over
Aging
Aging - metabolism
Benzamides - pharmacokinetics
Biological Availability
BMI
Body Mass Index
Brain - metabolism
Confidence intervals
Dopamine
Dopamine D2 receptor
Female
Gastrointestinal surgery
Humans
Hypotheses
Male
Midbrain
Middle Aged
Molecular Imaging - methods
Obesity
Positron-Emission Tomography - methods
Pyrrolidines - pharmacokinetics
Radiopharmaceuticals - pharmacokinetics
Receptors, Dopamine D2 - metabolism
Receptors, Dopamine D3 - metabolism
Reproducibility of Results
Sensitivity and Specificity
Statistics as Topic
Striatum
Studies
Tissue Distribution
Weight control
Young Adult
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Summary:The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects' ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese. 130 healthy subjects between 18 and 81years old underwent PET with [18F]fallypride, a high affinity DRD2/3 ligand. As expected, DRD2/3 availability declined with age. Critically, age significantly interacted with DRD2/3 availability in predicting BMI in the midbrain and striatal regions (caudate, putamen, and ventral striatum). Among subjects under 30years old, BMI was not associated with DRD2/3 availability. By contrast, among subjects over 30years old, BMI was positively associated with DRD2/3 availability in the midbrain, putamen, and ventral striatum. The present results are incompatible with the prominent dopaminergic hypofunction hypothesis that proposes that a reduction in DRD2/3 availability is associated with increased BMI, and highlights the importance of age in assessing correlates of DRD2/3 function. •Age interacted with DRD2 availability in predicting BMI•Among subjects under 30years old, BMI was not associated with DRD2 availability.•Among subjects over 30years old, BMI positively associated with DRD2 availability.•Present results are incompatible with the dopaminergic hypofunction hypothesis.•Results highlight the importance of age in assessing correlates of DRD2 function.
ISSN:1053-8119
1095-9572
DOI:10.1016/j.neuroimage.2016.05.044