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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    • "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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    ABSTRACT: Earlier findings show seasonality in processes and behaviors such as brain plasticity and depression that in part are regulated by Brain-Derived Neurotrophic Factor (BDNF). Based on this we investigated seasonal variation in serum BDNF concentrations in 2,851 persons who took part in the Netherlands Study of Depression and Anxiety (NESDA). Analyses by month of sampling (monthly n's >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001) with increasing concentrations in the spring-summer period (standardized regression weight (ß) = 0.19, P<.0001) and decreasing concentrations in the autumn-winter period (ß = -0.17, P<.0001). Effect sizes [Cohen's d] ranged from 0.27 to 0.66 for monthly significant differences. We found similar seasonal variation for both sexes and for persons with a DSM-IV depression diagnosis and healthy control subjects. In explorative analyses we found that the number of sunshine hours (a major trigger to entrain seasonality) in the week of blood withdrawal and the 10 weeks prior to this event positively correlated with serum BDNF concentrations (Pearson's correlation coefficients ranged: 0.05 - 0.18) and this could partly explain the observed monthly variation. These results provide strong evidence that serum BDNF concentrations systematically vary over the year. This finding is important for our understanding of those factors that regulate BDNF expression and may provide novel avenues to understand seasonal dependent changes in behavior and illness such as depression. Finally, the findings reported here should be taken into account when designing and interpreting studies on BDNF.
    PLoS ONE 11/2012; 7(11):e48046. DOI:10.1371/journal.pone.0048046 · 3.23 Impact Factor
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    • "Low 5-HTT binding activity was found in the dorsolateral prefrontal cortex of healthy co-twins of patients with mood disorders (Frokjaer et al, 2009), indicating a genetic vulnerability that may contribute to the pathophysiology of depression. Elevated 5-HTT levels in affect-modulating brain regions have been shown during the winter relative to the summer months (Kalbitzer et al, 2010; Praschak-Rieder et al, 2008; Ruhe et al, 2009), a finding of relevance to seasonal affective disorder pathology. Persistent reductions in 5-HT 1A receptors have been shown in patients fully recovered from a major depressive episode (Bhagwagar et al, 2004), implying that reduced 5-HT 1A availability may predispose to MDD, or be a result of the illness. "
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    ABSTRACT: The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 03/2012; 32(7):1426-54. DOI:10.1038/jcbfm.2012.20 · 5.41 Impact Factor
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    • "Epistatic effects have also been found in children and in the elderly where the interaction between BDNF Met allele, 5-HTT short allele, and environmental modifiers modulated the risk of depression (Kaufman et al. 2006; Kim et al. 2007). Moreover, serotonin transporter binding levels in the brain have been shown to increase during autumn and winter and as brain tryptophan levels decrease during the peripartum period; these factors could influence serotonin availability and in turn the risk of depression (Bailara et al. 2006; Praschak-Rieder et al. 2008; Schrocksnadel et al. 2003). Disruption of normal circadian rhythmicity has been investigated in psychiatric illness (Monteleone and Maj 2008). "
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    ABSTRACT: Postpartum depression (PPD) is an often underdiagnosed and undertreated mood disorder, with negative impact on the mother's and infant's health. Seasonal variation has been discussed as a risk factor for PPD. Candidate genes, such as those encoding for the brain-derived neurotrophic factor (BDNF), serotonin transporter (5-HTT), and Period2 (PER2), have been associated with depression and seasonal disorders. The present study is aimed to examine whether functional polymorphic variants, BDNF Val66Met, 5-HTTLPR, or PER2 SNP 10870, are associated with PPD symptoms and whether these genetic polymorphisms interact with season in predicting PPD symptoms. This case-control study comprised of 275 women from a population-based cohort of delivering women in Sweden, who completed a questionnaire containing the Edinburgh postnatal depression scale (EPDS) at 6 weeks and 6 months postpartum. Stressful life events (SLEs) and maternity stressors were also assessed. The results did not reveal any statistically significant overall association between the studied genetic polymorphisms and PPD symptoms. However, a significant association between BDNF Met66 carrier status and development of PPD symptoms at 6 weeks postpartum, even when controlling for prepartum and postpartum environmental risk factors, was evident among mothers delivering during autumn/winter. No gene-gene interactions were found but a cumulative effect was detected with carriers of a greater number of 5-HTTLPR S and BDNFVal66Met Met alleles reporting higher EPDS scores, if delivered during autumn/winter. Our findings propose a role of the BDNF gene in the development of PPD symptoms, potentially mediated by season of delivery.
    Archives of Women s Mental Health 12/2011; 14(6):453-63. DOI:10.1007/s00737-011-0239-x · 2.16 Impact Factor
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