I have to admit, I
retain some skepticism about the concept of Seasonal
Affective Disorder. Research such as the topic of
this post helps, though, to lend some credibility to the concept.
It is true that exposure to bright light therapy (BLT) can alleviate symptoms of SAD. That alone would seem to verify the validity of the diagnosis. However, there is evidence (1 2) that BLT can alleviate symptoms in non-seasonal depression, too.
I know that some of my skepticism comes from the cute acronyms, SAD and BLT. Not very scientific, I suppose, but cute acronyms bug me.
Anyway, there is an open-access article that demonstrates reasonably consistent changes in the functioning of serotonin transporters in persons with SAD. The transporters are more active in symptomatic SAD patients, in winter. They are closer to normal in SAD patients during the summer, and SAD patients who respond to BLT.
Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder
Matthäus Willeit, Harald H Sitte, Nikolaus Thierry, Klaus Michalek, Nicole Praschak-Rieder, Peter Zill, Dietmar Winkler, Werner Brannath, Michael B Fischer, Brigitta Bondy, Siegfried Kasper, and Ernst A Singer
Neuropsychopharmacology (2008) 33, 1503-1513; doi:10.1038/sj.npp.1301560; published online 19 September 2007
Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (rho=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.
Serotonin transporters are little
protein structures embedded in the
cell membrane of neurons, specifically, neurons that release serotonin.
They are the most important regulators of the concentration
of serotonin in the little space between nerve cells. Previous
research has demonstrated that there are genetically-based
differences (polymorphism) in the efficiency of these transporters,
from one person to another. Furthermore, there is evidence (1 2) that the genetic differences can affect how a person responds to an antidepressant, and what adverse effect burden may occur. These findings (and many, many more) all lend support to the notion that serotonin is involved in the development of depression. The Willeit paper, by itself, does not prove much. But added to the weight of the previous studies, it does tend to confirm the validity of SAD as a meaningful diagnostic entity.
So, the Willeit study adds to the value of the previous research of serotonin transporters. But the other side of the coin, is that the validity of the study rests upon the validity of all the other work done on the role of serotonin in depression.
Most thoughtful people[citation needed] think that the serotonin hypothesis is only part of the story of the pathophysiology of depression. Some are openly dismissive. But even if it is only a small part of the story, it does serve to direct research efforts.
You have to start somewhere, and the serotonin hypothesis has turned out to be a good starting point.
It is clear from the Willeit paper that there is something important happening with serotonin transporters in the patients they studied, and that the something-that-happens is correlated with treatment response. It is hard to argue with success.
Brain & Behavior
Comments
This is interesting to me on another level.
A couple years ago I was involved in a study during which we chronically cold-stressed rats (a model for depression) and observed the ultrastructural alterations in the 5-HT and NE transporters'(SERT and NET) expression along the Plasma membrane of different 5-HT and NE projections to the PFC. The NET expression changed, but the SERT did not. We thought there might be different regulatory mechanisms involved between the two monamine systems we looked at. This could be it--or at least one of them.
Posted by: NeuroTrumpet | May 22, 2008 8:22 AM
As a sufferer, I must wholeheartedly insist that SAD is a real phenomenon. Whether it is caused or enhanced by a lack of daylight hours or adequate sunlight is not something I can speak to; I tend to spend most of my waking hours under fluorescent lights all year long. I have found that light therapy helps, but I still delight in long hours of sunlight outside my windows and dread the short hours of winter sunlight, despite the fact that my body dislikes the heat of summer and rejoices in the cool of (coastal California) winter. (On the other hand, bacon/lettuce/tomato sandwiches don't help at all. So much for acronyms. :-) )
Posted by: Karen | May 22, 2008 8:53 AM
This observation from the paper:
5-HTTLPR was not associated with any of the 5-HTT parameters.
would seem to be at odds with your observation :
My reading is that despite a unending drumbeat of papers showing correlations of SERT promotor genotype with various behavioral or affective phenotypes, the story is lacking in meat. I.e., a direct demonstration of functional differences in serotonin function in the intact organism. As you are aware, there are many regulatory, and possibly compensatory, steps between a genotypic difference (in the promotor, no less), expression of the transporter and function of a neurochemical system in vivo!
I should note that M. mulatta expresses a similar polymorphism (although the closely related M. fascicularis may not, weirdly) and there have been no good demos in that species either. Correlations and indirect measures look promising. But say a microdialysis or well-controlled tissue study? not so much.
Posted by: DrugMonkey | May 22, 2008 11:47 AM