Deborah Brauser

October 29, 2014

BERLIN ― Seasonal affective disorder (SAD) may be caused by seasonal changes in striatal serotonin transporter (SERT) binding, new research suggests.

Dr Brenda McMahon

A small imaging study showed that patients in Denmark with SAD had significantly greater SERT fluctuations from summer to winter than their healthy peers. Those with SAD also showed higher levels of SERT activity in the winter months, signaling lower serotonin activity.

"We believe that we have found the dial the brain turns when it has to adjust serotonin to the changing seasons," lead author Brenda McMahon, MD, from the Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet in Denmark, said in a release.

"I think this is a beginning to understanding different causes of seasonal affective disorder," she added in a statement to Medscape Medical News.

The study was presented here at the 27th European College of Neuropsychopharmacology (ECNP) Congress.

First Longitudinal Study

"Lack of daylight is a prominent environmental stressor at high latitudes," the investigators write, noting that approximately 15% of the Copenhagen population has full or subsyndromal SAD.

Dr McMahon noted that SERT "carries serotonin back into the nerve cells, where it is not active," so the higher the SERT activity, the lower the serotonin activity.

"Sunlight keeps this setting naturally low, but when the nights grow longer during the autumn, the SERT levels increase, resulting in diminishing active serotonin levels."

She explained that most individuals are not affected by SAD and do not have an increase in SERT activity. This means that active serotonin levels for healthy individuals stay high throughout the winter.

Interestingly, carriers of the short 5-HTTLPR polymorphism (S-carriers) have been shown to have higher SERT binding in the winter than in the summer.

The researchers note that this is the first longitudinal study to assess and compare seasonal SERT fluctuations in two groups of S-carriers ― those with and those without SAD.

The Seasonal Pattern Assessment Questionnaire was administered to 40 participants to measure seasonal variations in sleep, mood, appetite and weight, energy, and social activity. Scores for each item were added together to form a global seasonality score (GSS).

Seventeen of the participants had a GSS score of 11 or higher, indicating presence of SAD. This was confirmed by interviews during both asymptomatic and symptomatic (winter) phases. Of these individuals, 11 were S-carriers (55% female; mean age, 26 years; mean GSS score, 13.7).

The other 23 total participants (56.5% female; mean age, 25 years; all S-carriers) had GSS scores of 10 or lower (mean score, 4.8) and were classified as the "healthy controls group."

In random order, all participants underwent dynamic 11C dimethylaminomethylphenyl-sulfanyl benzonitrile positron emission tomography (DASB-PET) scans in both the summer and the winter.

"Nondisplaceable binding potential (BPND) was quantified [and] summer BPNDs were plotted as a function of winter BPNDs for 17 different brain regions," explain the investigators.

"The slope of the regression line...was used as a measure of individual change in global brain SERT changes across seasons," they add.

Higher Wintertime SERT

Results showed that, when examining relative change in SERT (relBPND), the S-carriers in the SAD group had significantly higher SERT in the winter than in the summer (0.51 vs 0.45, P = .035).

On the other hand, for the healthy controls group, the opposite was true ― SERT was significantly higher in the summer than the winter (0.49 vs 0.46, P = .01).

Dr McMahon said that this was surprising, especially because this group consisted of S-carriers.

"But when we looked into this, we found that it could be because we so carefully selected a group with almost no seasonality-related symptoms. So they were actually almost over-healthy," she added.

When the investigators "tested if relBPND predicted the relative change in symptom scores from winter to summer" in the SAD S-carriers, they found that a larger seasonal difference was associated with the largest difference in SAD symptoms (P = .003).

Overall, "healthy individuals downregulate their SERT in winter compared to summer, and SAD patients upregulate their cerebral SERT to an extent that correlates with their SAD symptom severity," the researchers write.

They add that the findings suggest a failure in SAD to regulate cerebral SERT appropriately during winter stressors, "thereby contributing to the development of SAD symptoms."

Dr McMahon noted that although the study does not answer whether these are primary or secondary mechanisms, it does show a link. She added that it would be interesting to see whether there is any difference in response to light therapy or selective serotonin reuptake inhibitors (SSRIs) among the S-carriers.

"That would be something interesting to look at in the future. Right now, we aren't able to predict treatment response because we didn't look at that. But hopefully this is a first step."

"Brain Switch" Finding

ECNP president Guy Goodwin, FMedSci, noted in a pre-event interview with Medscape Medical News that this was among the hottest topics to be presented at the meeting.

Dr Guy Goodwin

"Preliminary scan of the posters this year suggests important findings in a number of areas, including findings on seasonality ― with evidence suggesting a switch that the brain turns on when it has to adjust the serotonin levels to a change in season in SAD," said Dr Goodwin, who is also professor of psychiatry at the University of Oxford, United Kingdom.

Siegfried Kasper, MD, professor and chairman in the Department of Psychiatry and Psychotherapy at the Medical University of Vienna, Austria, noted in a release that previous research has shown an association between SERT fluctuations and SAD.

"But this is the first study to follow patients through summer and winter comparisons. It seems to offer confirmation that SERT is associated with SAD," said Dr Kasper.

The investigators report no relevant financial relationships.

27th European College of Neuropsychopharmacology (ECNP) Congress. Abstract P.1.i.037. Presented October 21, 2014.

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