Seasonal Changes in Brain Serotonin Transporter Binding in Short Serotonin Transporter Linked Polymorphic Region-Allele Carriers but Not in Long-Allele Homozygotes

Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Biological psychiatry (Impact Factor: 9.47). 06/2010; 67(11):1033-9. DOI: 10.1016/j.biopsych.2009.11.027
Source: PubMed

ABSTRACT A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with seasonality both in patients with seasonal affective disorder and in the general population.
We used in vivo molecular imaging to measure cerebral serotonin transporter (5-HTT) binding in 57 healthy Scandinavians and related the outcome to season of the year and to the 5-HTTLPR carrier status.
We found that the number of daylight minutes at the time of scanning correlated negatively with 5-HTT binding in the putamen and the caudate, with a similar tendency in the thalamus, whereas this association was not observed for the midbrain. Furthermore, in the putamen, an anatomic region with relatively dense serotonin innervation, we found a significant gene x daylight effect, such that there was a negative correlation between 5-HTT binding and daylight minutes in carriers of the short 5-HTTLPR allele but not in homozygote carriers of the long allele.
Our findings are in line with S-carriers having an increased response in neural circuits involved in emotional processing to stressful environmental stimuli but here demonstrated as a endophenotype with dynamic changes in serotonin reuptake.

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    • "Comparisons of 5-HTT binding in subjects with different 5-HTTLPR genotypes have been controversial since some studies have not been able to demonstrate any impact of genotype on 5-HTT function in vivo (Murthy et al., 2010; Parsey et al., 2006; Shioe et al., 2003) or post-mortem tissue (Mann et al., 2000). However, such lack of effects of 5- HTTLPR on altered 5-HTT binding can be explained by developmental or environmental rather than direct effects of 5-HTTLPR on adult serotonergic neurotransmission (Gaspar et al., 2003; Kalbitzer et al., 2010; Parsey et al., 2006; Willeit et al., 2008). Moreover, 5-HTTLPR genotypes seem to be affected by epigenetic mechanisms (Alasaari et al., 2012; Kinnally et al., 2010; van IJzendoorn et al., 2010), which could further explain inconclusive findings. "
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    • "As measured by the levels of 5-HT and its metabolites in the blood, 5-HT turnover is lowest in the winter and the rate of its production rises in response to the duration of bright light (Lambert et al., 2002). In addition , in vivo measures of SERT binding in the human brain show that SERT binding activity is greatest in the fall and winter and decreases in correlation with the duration of bright light as days lengthen (Praschak-Rieder et al., 2008; Willeit et al., 2008; Kalbitzer et al., 2010). Finally, at the therapeutic level, in addition to the efficacy of light therapy in alleviating SAD, pharmacotherapy with SSRIs is also effective (Ruhrmann et al., 1998; Lam et al., 2006; Pae et al., 2008; Pjrek et al., 2009). "
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