alt="ResearchBlogging.org"
src="http://www.researchblogging.org/images/rbicons/ResearchBlogging-Medium-White.png"
align="left" border="0" height="50" hspace="3"
vspace="3" width="80">I have to admit, I
retain some skepticism about the concept of href="http://scienceblogs.com/clock/2008/04/seasonal_affective_disorder_th_2.php">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 ( href="http://www.ncbi.nlm.nih.gov/pubmed/9609674">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.

href="http://www.nature.com/npp/journal/v33/n7/full/1301560a.html">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.   href="http://www3.interscience.wiley.com/journal/40002542/abstract?CRETRY=1&SRETRY=0">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 ( href="http://archpsyc.ama-assn.org/cgi/content/full/61/11/1163">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 href="http://archpsyc.ama-assn.org/cgi/content/full/61/11/1163">serotonin
hypothesis is only part of the story of
the pathophysiology
of depression.  Some are href="http://www.badscience.net/?p=607">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.