5-HTT

It is the time of the year again. Seasonal Affective Disorder is in the news again. For a description and treatment of SAD see a previous article on this blog from about one year ago: 8 Articles about Seasonal Affective Disorder. You can also watch a video on SAD, with advice about how to cope with this disease.

Serotonin is an important neurotransmitter in SAD because in post mortem human brain samples, serotonin concentrations are lowest in people dying in the winter. Also, the concentration of the serotonin metabolite 5-HIAA is lower in jugular blood samples collected in winter. This might be due to seasonal changes in the activity of plasma-membrane serotonin transporter (5-HTT) that serves a central role in neural serotonin transmission. The serotonin binding potentials were significantly higher during the fall and winter months than in the spring and summer, indicating that less serotonin circulates in the brain during the darker, colder time of the year.

The serotonin transporter protein has different functional genetic variants. The serotonin transporter gene is polymorphic.The polymorphism that is considered most relevant is an insertion/deletion polymorphism in the promoter region of the gene, which encodes for the serotonin transporter.

The serotonin transporter gene (5-HTTLPR) gene has two variant alleles: a short (S) and a long (L) allele. The S allele has been associated with a nearly 50% reduction in expression of the serotonin transporter protein, vulnerability for mood disorders, inadequate response to SSRIs and side-effects.

In comparison to L-allele homozygotes, S-allele carriers have increased propensity to develop mood disorders in response to seasonal changes.

In a recent research: Seasonal changes in brain serotonin transporter binding in short 5-
HTTLPR-allele carriers but not in long-allele homozygotes, the following results emerged:

we found that the 5-HTT binding in carriers of the S-allele is affected by seasonal changes, but not in carriers of the L-allele. We found the strongest seasonal effect in the putamen, an anatomical region with a dense serotonin innervation, that is implicated in motor functions, but also in processing of aversive stimuli. We did not find any seasonal variation in midbrain, where the serotonergic cell bodies are located.

The polymorphism with carriers of the short (S-allele) and seasonal changes, when there is fewer hours of sunlight each day can be another gene environment interaction resulting in SAD.

Kalbitzer, Jan, Erritzoe, David, Holst, Klaus, Nielsen, Finn , Marner, Lisbeth, Lehel, Szabolcs, Arentzen, Tine, Jernigan, Terry, and Knudsen, Gitte . Seasonal changes in brain serotonin transporter binding in short 5-HTTLPR-allele carriers but not in long-allele homozygotes. Available from Nature Precedings(2008)