title: Quantification of the Serotonin 1A Receptor Using PET: Identification of a Potential Biomarker of Major Depression in Males.
abstract: 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, p<0.0001). The greatest difference between MDD subjects and controls was in the raphe (132%, p=0.000). Furthermore, by using a threshold, male controls can be distinguished from depressed males with high sensitivity and specificity (both >80%). 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.
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kaufman
authors.affiliation: Columbia University College of Physicians and Surgeons, New York City, NY, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sullivan
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Columbia University School of Public Health, New York City, NY, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.affiliation: Columbia University College of Physicians and Surgeons, New York City, NY, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Miller
authors.affiliation: Columbia University College of Physicians and Surgeons, New York City, NY, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Columbia University College of Physicians and Surgeons, New York City, NY, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.affiliation: Stony Brook University, Stony Brook, NY, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: DeLorenzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics; D011903:Raphe Nuclei / Q000000981:diagnostic imaging* / Q000473:pathology; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide