Quantification of the Serotonin 1A Receptor Using PET: Identification of a Potential Biomarker of Major Depression in Males

Multiple lines of research have implicated the serotonin 1A (5-HT1A) receptor in major depressive disorder (MDD). Despite this, quantification of 5-HT1A is yet to yield a clinically relevant MDD biomarker. One reason may be that reported sex differences in the serotonergic system confound the compar...

Full description

Saved in:
Bibliographic Details
Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2015-06, Vol.40 (7), p.1692-1699
Main Authors: Kaufman, Joshua, Sullivan, Gregory M, Yang, Jie, Ogden, R Todd, Miller, Jeffrey M, Oquendo, Maria A, Mann, J John, Parsey, Ramin V, DeLorenzo, Christine
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Biomarkers
Carbon Isotopes - pharmacokinetics
Depressive Disorder, Major - diagnostic imaging
Depressive Disorder, Major - metabolism
Estrogens
Females
Gender differences
Genotype
Health care
Humans
Magnetic Resonance Imaging
Male
Males
Mental depression
Middle Aged
Original
Pathophysiology
Piperazines - pharmacokinetics
Positron-Emission Tomography
Pyridines - pharmacokinetics
Raphe Nuclei - diagnostic imaging
Raphe Nuclei - pathology
Receptor, Serotonin, 5-HT1A - genetics
Receptor, Serotonin, 5-HT1A - metabolism
Serotonin
Serotonin Antagonists - pharmacokinetics
Sex Characteristics
Sexes
Tomography
Womens health
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Multiple lines of research have implicated the serotonin 1A (5-HT1A) receptor in major depressive disorder (MDD). Despite this, quantification of 5-HT1A is yet to yield a clinically relevant MDD biomarker. One reason may be that reported sex differences in the serotonergic system confound the comparison between diagnostic groups. Therefore, this study sought to determine whether differences in 5-HT1A binding between depressed and control subjects are affected by sex. Using positron emission tomography (PET), serotonin 1A binding was quantified in 50 patients with MDD (34 female, 16 male) and 57 healthy controls (32 female, 25 male). The subjects' 5-HT1A density (BPF, equal to the product of the density of available receptors and tracer affinity), was determined by using the PET tracer [carbonyl-C-11]-WAY-100635, a selective 5-HT1A antagonist. Results indicated that male MDD subjects had a 67.0% higher BPF across 13 brain regions compared with male controls (df=103, p80%). In females, the separation between diagnostic groups yields much lower sensitivity and specificity. This data therefore suggests a specific biosignature for MDD in males. Identification of such a biosignature could provide a deeper understanding of depression pathology, help identify those at highest risk, and aid in the development of new therapies. Further, these findings suggest that combining male and female cohorts may not be optimal for some MDD studies.
ISSN:0893-133X
1740-634X
DOI:10.1038/npp.2015.15