Abstract

Objectives: Lack of daylight is a prominent environmental stressor at high latitudes. It is estimated that more than 15a of the Copenhagen inhabitants suffer from Seasonal Affective Disorder (SAD) or sub-syndromal SAD [1]. Cross-sectional neuroimaging studies have demonstrated that in healthy individuals, striatal serotonin transporter (SERT) binding is high at winter solstice and low at summer solstice. These fluctuations are particularly evident in carriers of the short 5-HTTLPR polymorphism (S-allele carriers). The aim of the present study is to do the first longitudinal investigation of seasonal SERT fluctuations in healthy S-allele carriers and in S-allele carriers suffering from SAD. Methods: All participantscompleted the Seasonal Pattern Assessment Questionnaire (SPAQ) to evaluate seasonal variations in sleep, social activity, mood, weight, appetite and energy. The score on each item was summed to obtain a Global Seasonality Score (GSS), which indexes the degree of winter depression (range: 0–24, GSS>10 indicates SAD). Subjects without any seasonality and a GSS equal to or less than 10 entered the study as healthy participants while subject with a GSS score equal to or higher than 11 were interviewed by specialized psychiatrists both in their asymptomatic and their symptomatic (winter) phase to establish the SAD diagnosis. Twenty-three (13 females) healthy S-allele carriers (mean±SD: GSS: 4.8±2 and age: 25±7 years) and 11 (six females) Sallele carrying SAD patients (mean±SD: GSS:13.7±2 and age: 26±8 years) were investigated with a dynamic [ 11 C]DASB HRRT PET scan and a MRI brain scan both summer and winter, in randomized order. Non-displaceable binding potential (BP ND ) was quantified using MRTM2. Summer BP ND s were plotted as a function of winter BP ND s for 17 different brain regions [2]. The slope of the regression line (β) was used as a measure of individual change in global brain SERT changes across seasons. β values were compared between healthy controls and SAD patient using a Mann–Whitney unpaired t-test. A one sample paired t-test was used within groups to investigate significant seasonal SERT changes. Results: We found a significant difference between healthy controls and SAD patients in seasonal SERT changes: median β healthy controls: 1.033, median β SAD: 0.93, U=59, p=0.01. Furthermore we observed a tendency for a winter-summer change in the SAD group (β≠1): t(10)=2.136, meanβ±SD: 0.96±0.07, p=0.058 but not in the healthy control group: t(22)=1.759, mean β±SD: 1.024±0.07, p=0.092. Conclusions: We find that SAD patients experience a significantly larger seasonal SERT fluctuation compared to their healthy counterparts. We were not able to reproduce previous findings of a similar up-regulation during winter in healthy subjects and we speculate that this is due to a careful selection of individuals completely void of season related symptoms. Our data suggests that seasonally provoked depression is linked to seasonal SERT changes.

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