title: Diurnal and seasonal variation of the brain serotonin system in healthy male subjects.
abstract: The mammalian circadian clock underlies both diurnal and seasonal changes in physiology, and its function is thought to be disturbed in both seasonal and non-seasonal depression. In humans, molecular imaging studies have reported seasonal changes in the serotonin system. Despite the role of the circadian clock in generating seasonal physiological changes, however, diurnal variation of serotonin receptors and transporters has never been directly studied in humans. We used positron emission tomography to examine diurnal and seasonal changes in the serotonin 5-HT1A receptor and serotonin transporter in two large cohorts of healthy male subjects, employing a cross-sectional design. In 56 subjects measured with [(11)C]WAY-100635, we observed diurnal increases in the availability of 5-HT1A receptors in the cortex. In 40 subjects measured with [(11)C]MADAM, a decrease in 5-HTT was observed in the midbrain across the day. We also found seasonal changes in the 5-HT1A receptor in serotonin projection regions, with higher availability on days with a longer duration of daylight. Our observation that serotonin receptor and transporter levels may change across the day in humans is corroborated by experimental research in rodents. These findings have important implications for understanding the relationship between the circadian and serotonin systems in both the healthy brain and in affective disorders, as well as for the design of future molecular imaging studies.
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Experimental Psychology, Utrecht University, Utrecht, The Netherlands; Stockholm Brain Institute, Stockholm, Sweden. Electronic address: granville.matheson@ki.se.
authors.forename: Granville J
authors.initials: GJ
authors.lastname: Matheson
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schain
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rita
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lundberg
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden; AstraZeneca Translational Science Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Cselényi
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Borg
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden; AstraZeneca Translational Science Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Brain Institute, Stockholm, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Cervenka
mesh_terms: D000328:Adult; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000494:pharmacology; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012621:Seasons; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D001596:Benzylamines; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: Circadian; Depression; Human; PET; Seasonal; Serotonin