Seasonal Variation in Human Brain Serotonin Transporter Binding

Vivian M. Rakoff PET Imaging Centre, Centre for Addiction and Mental Health, 250 College St, Toronto, ON M5T 1R8, Canada.
Archives of general psychiatry (Impact Factor: 14.48). 09/2008; 65(9):1072-8. DOI: 10.1001/archpsyc.65.9.1072
Source: PubMed


It is a common experience in temperate zones that individuals feel happier and more energetic on bright and sunny days and many experience a decline in mood and energy during the dark winter season. Brain serotonin is involved in the regulation of physiologic functions, such as mating, feeding, energy balance, and sleep. Although these behaviors and serotonin-related conditions show a clear seasonal pattern in humans, the molecular background of seasonal changes in serotonin function is entirely unknown. The serotonin transporter is a key element in regulating intensity and spread of the serotonin signal.
To detect seasonal variations in serotonin transporter binding in the living human brain and to detect correlations between serotonin transporter binding and duration of daily sunshine.
Regional serotonin transporter binding potential values, an index of serotonin transporter density, were assessed from December 1, 1999, to December 9, 2003, in a consecutive sample of healthy volunteers. Binding potential values were related to meteorologic data.
Tertiary care psychiatric hospital.
Volunteer sample of 88 drug-naive healthy individuals.
Carbon 11-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile positron emission tomography.
Regional serotonin transporter binding potential values.
Serotonin transporter binding potential values were significantly higher in all investigated brain regions in individuals investigated in the fall and winter compared with those investigated in the spring and summer (P = .01 to .001). Moreover, binding potential values showed negative correlations with average duration of daily sunshine in all brain regions (rho = -0.21 to -0.39; P = .05 to <.001), such that higher values occurred at times of lesser light.
Serotonin transporter binding potential values vary throughout the year with the seasons. Since higher serotonin transporter density is associated with lower synaptic serotonin levels, regulation of serotonin transporter density by season is a previously undescribed physiologic mechanism that has the potential to explain seasonal changes in normal and pathologic behaviors.

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    • "These findings suggest a possible relationship between seasonal variation of serotonin transporters and suicide. Because sunshine has been reported to be associated with alterations in the serotonergic system (Lambert et al. 2002;Praschak-Rieder et al. 2008; Sansone and Sansone 2013) and with suicide rate in Australia and in Austria (Lambert et al. 2003;Vyssoki et al. 2014), we analyzed whether sunshine duration was associated with suicide. We found no evidence of an association between sunshine duration and suicide in our study cities, regardless of the lag period. "
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    ABSTRACT: A limited literature base suggests that ambient temperature contributes to suicide, with studies typically focused on a single nation using temporal and spatial aggregated data. We evaluated an association between ambient temperature and suicide in multiple cities in three East Asian countries. A time-stratified case-crossover method was used to explore the relationship between temperature and suicide, adjusting for potential time-varying confounders and time-invariant individual characteristics. Gender- and age-specific associations of temperature with suicide were estimated, as were interactions between temperature and these variables. A random-effects meta-analysis was used to estimate country-specific pooled associations of temperature with suicide. An increase in temperature corresponding to half of the city-specific standard deviation was positively associated with suicide in most cities, although average suicide rates varied substantially. Pooled country-level effect estimates were 7.8% (95% CI: 5.0, 10.8%) for a 2.3ºC increase in ambient temperature in Taiwan, 6.8% (95% CI: 5.4, 8.2%) for a 4.7ºC increase in Korea, and 4.5% (95% CI: 3.3, 5.7%) for a 4.2ºC increase in Japan. The association between temperature and suicide was significant even after adjusting for sunshine duration; the association between sunshine and suicide was not significant. The associations were greater among men than women in 12 of the 15 cities although not significant. There was little evidence of a consistent pattern of associations with age. In general, associations were strongest with temperature on the same day or the previous day, with little evidence of associations with temperature over longer lags (up to 5 days). We estimated consistent positive associations between suicide and higher ambient temperature in three East Asian countries, regardless of country, gender, and age.
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    • "studies of5HT, dopamine, melatonin and other central neurotransmitters show clock-like rhythms displaying annual, seasonal, monthly, weekly (infradian), daily (circadian)and near-hourly (ultradian) periods (Table I). For example, at the slower end of the cycling spectrum, seasonal variations in 5HT levels and reuptake transporter binding in the brain are observed throughout the year (Praschak-Rieder et al. 2008). These switches are triggered in part by environmental events. "
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    ABSTRACT: Oscillations in brain activities with periods of minutes to hours may be critical for normal mood behaviors. Ultradian (faster than circadian) rhythms of mood behaviors and associated central nervous system activities are altered in depression. Recent data suggest that ultradian rhythms in serotonin (5HT) function also change in depression. In two separate studies, 5HT metabolites in cerebrospinal fluid (CSF) were measured every 10 m for 24 h before and after chronic antidepressant treatment. Antidepressant treatments were associated with enhanced ultradian amplitudes of CSF metabolite levels. Another study used resting-state functional magnetic resonance imaging (fMRI) to measure amplitudes of dorsal raphé activation cycles following sham or active dietary depletions of the 5HT precursor (tryptophan). During depletion, amplitudes of dorsal raphé activation cycles increased with rapid 6 s periods (about 0.18 Hz) while functional connectivity weakened between dorsal raphé and thalamus at slower periods of 20 s (0.05 Hz). A third approach studied MDMA (ecstasy) users because of their chronically diminished 5HT function compared to non-MDMA polysubstance users (Karageorgiou et al., 2009). Compared to a non-MDMA using cohort, MDMA users showed diminished fMRI intra-regional coherence in motor regions along with altered functional connectivity, again suggesting effects of altered 5HT oscillatory function. These data support a hypothesis that qualities of ultradian oscillations in 5HT function may critically influence moods and behaviors. Dysfunctional 5HT rhythms in depression may be a common endpoint and biomarker for depression, linking dysfunction of slow brain network oscillators to 5HT mechanisms affected by commonly available treatments. 5HT oscillatory dysfunction may define illness subtypes and predict responses to serotonergic agents. Further studies of 5HT oscillations in depression are indicated. Synapse, 2013. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2013 · Synapse
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    • "Although the underlying mechanisms of seasonality in depressive behaviors could not be elucidated yet, some data point to variation in serotonin (5-hydroxytryptamine; 5-HT) expression as being the molecular mechanism that thrives this association [13], [14]. Indeed, human studies show that central and peripheral 5-HT activity undergoes marked seasonal rhythmicity [13]–[19]. "
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