title: Increased Seasonal Variation in Serotonin Transporter Binding in Seasonal Affective Disorder.
abstract: Seasonal affective disorder (SAD) is highly prevalent with rates of 1-6% and greater prevalence at more extreme latitudes; however, there are almost no direct brain investigations of this disorder. In health, serotonin transporter binding potential (5-HTT BPND), an index of 5-HTT levels, is greater throughout the brain in fall-winter compared with spring-summer. We hypothesized that in SAD, this seasonal variation would be greater in brain regions containing structures that regulate affect such as the prefrontal and anterior cingulate cortices (PFC and ACC). Furthermore, given the dimensional nature of SAD symptoms, it was hypothesized that seasonal fluctuation of 5-HTT BPND in the PFC and ACC would be greatest in severe SAD. Twenty SAD and twenty healthy participants underwent [(11)C]DASB positron emission tomography scans in summer and winter to measure seasonal variation in [(11)C]DASB 5-HTT BPND. Seasonal increases in [(11)C]DASB 5-HTT BPND were greater in SAD compared with healthy in the PFC and ACC, primarily due to differences between severe SAD and healthy (severe SAD vs healthy; Mann-Whitney U, U=42.5 and 37.0, p=0.005 and 0.003, respectively; greater magnitude in severe SAD of 35.10 and 14.23%, respectively), with similar findings observed in other regions (U=40.0-62.0, p=0.004-0.048; greater magnitude in severe SAD of 13.16-17.49%). To our knowledge, this is the first brain biomarker identified in SAD. This creates a new opportunity for phase 0 studies to target this phenotype and optimize novel prevention/treatment strategies for SAD.
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, CAMH Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Tyrer
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, CAMH Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Levitan
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, CAMH Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, CAMH Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, CAMH Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Behavioural Neurobiology Laboratory, Departments of Psychiatry, Pharmacology and Toxicology, and Psychology, Campbell Family Mental Health Research Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, CAMH Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, and Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000328:Adult; D001596:Benzylamines / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D016574:Seasonal Affective Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D012621:Seasons; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins