Diurnal and seasonal variation of the brain serotonin system in healthy male subjects

Neuroimage. 2015 May 15;112:225-231. doi: 10.1016/j.neuroimage.2015.03.007. Epub 2015 Mar 12.


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.

Keywords: Circadian; Depression; Human; PET; Seasonal; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Benzylamines
  • Brain / diagnostic imaging*
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Cerebral Cortex / metabolism
  • Circadian Rhythm / physiology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Piperazines / pharmacology
  • Positron-Emission Tomography
  • Pyridines / pharmacology
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Seasons*
  • Serotonin / metabolism
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Young Adult


  • Benzylamines
  • N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine
  • Piperazines
  • Pyridines
  • Radiopharmaceuticals
  • Serotonin Antagonists
  • Serotonin Plasma Membrane Transport Proteins
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide