Serotonin transporter genetics (5-HTT/SERT, 5-HTTLPR)

The serotonin transporter (5-HTT, also SERT) takes serotonin back into the cells after it has acted. Its gene is called SLC6A4. The test mainly looks at a length variant in the gene's control region, known as 5-HTTLPR, with a short (S) and a long form (L); which variants were determined is stated in the report. The sample is EDTA blood; as a genetic test, written consent is required. The serotonin transporter is part of the “Depression genetics” analysis and is listed in the test catalogue as 5HTT/SERT. The result stays the same for life.

What the serotonin transporter does in the body

Nerve cells release serotonin into the synaptic cleft, where it binds to receptors on the neighbouring cell. The transporter in the membrane of the sending cell then pumps it back together with sodium; there it is stored again or broken down by MAO-A. In this way the transporter helps to determine how long and how strongly serotonin acts. The same transporter sits on platelets, which thereby take up and store almost all the serotonin in the blood, and in the gut lining, where it clears serotonin released by the enterochromaffin cells and thus helps to control gut movement and secretion. Antidepressants of the SSRI group specifically inhibit this transporter.

What does the 5-HTTLPR variant mean for serotonin reuptake?

Compared with the long form (L), the short form (S) lacks a section of the control region. In cell studies, the gene with the S form was read more weakly, less transporter was produced and less serotonin was taken back. Within the long form there is a subvariant (LG, rs25531) that behaved similarly to the S form in cell studies; results are therefore often grouped into more strongly (LA) and more weakly read forms. Less transporter means that serotonin stays longer in the synaptic cleft, and platelets and the gut lining take it up more slowly. The S form is common worldwide; it occurs more frequently in East Asian than in European populations.

What can be read from the 5-HTTLPR genotype?

Hardly any gene variant has been studied as often in connection with mood and stress processing. A widely noticed study described in 2003 that carriers of the S form developed depressive symptoms more often after stressful life events. Large later analyses with many thousands of participants could not confirm this link; today it is considered disputed. Whether the variant influences how people respond to SSRIs has also been studied with inconsistent results. The genotype therefore describes an inherited property of serotonin reuptake, but not a personality trait and not a disease. Serotonin measured in blood mainly reflects the content of the platelets; it has its own page.

The interpretation is given in your report.