title: Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.
abstract: Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Brenda
authors.initials: B
authors.lastname: Mc Mahon
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Sofie B
authors.initials: SB
authors.lastname: Andersen
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Madsen
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Liv V
authors.initials: LV
authors.lastname: Hjordt
authors.affiliation: Psychiatric Centre Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Hageman
authors.affiliation: Psychiatric Centre Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Dam
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Sofi
authors.initials: S
authors.lastname: da Cunha-Bang
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Kettegård allé 30, 2650 Hvidovre, Denmark.
authors.forename: William
authors.initials: W
authors.lastname: Baaré
authors.affiliation: PET and Cyclotron Unit, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2100 Copenhagen, Denmark.
authors.forename: Lis
authors.initials: L
authors.lastname: Hasholt
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark Department of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Holst
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.affiliation: Neurobiology Research Unit, Rigshospitalet and Centre for Integrated Molecular Brain Imaging, Section 6931, Blegdamsvej 9, 2100 Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Denmark gmk@nru.dk.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D001596:Benzylamines / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D011374:Progesterone; D011569:Psychiatric Status Rating Scales; D011869:Radioligand Assay; D016574:Seasonal Affective Disorder / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D012621:Seasons; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014364:Tryptophan / Q000097:blood; 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; D011374:Progesterone; D004958:Estradiol; D014364:Tryptophan
keywords: PET; seasonal affective disorder; serotonin; serotonin transporter; serotonin transporter linked polymorphic region