Genetics, Depression, and Anxiety

5-HTTLPR is a polymorphic region in a region of the 17^th chromosome called SLC6A4. This means that different phenotypes can exist in that region. The entire gene codes for the serotonin transporter, but the 5-HTTLPR is part of the promoter region, which regulates how the gene functions.

Serotonin is a neurotransmitter within the body that is used to connect the body’s physical state with mood. For most living organisms, serotonin is released in response to the body’s reaction to the abundance or scarcity of resources. Based on this abundance or scarcity, serotonin is sent to your brain that puts you in an elevated or depressed mood.

So then with respect to the 5-HTTLPR, a SNP occurs in the rs25531 and rs25532 positions. This SNP determines if you have a “short” (S) allele or a “long” (L) allele. Within this region of the gene, the 5-HTTLPR contains several repeats of the same sequence. The short allele causes 14 repeats and the long allele causes 16 repeats.

Research has shown that presence of the long allele causes a higher rate of mRNA transcription for the serotonin transporter, which could have a positive impact on the mood of the individual. Several studies have shown higher rates of depression or anxiety disorders among people with the short allele.

This is an example of a gene-environment interaction, because the impact of the gene is altered in the presence of different environmental situations. It makes sense that a gene-environment interaction would occur since, in all cases, serotonin levels in the brain respond to environmental factors.

This has several applicable implications in the world today. The pharmaceutical industry earns a large portion of its money from the sale of antidepressants. That fact could provide a good explanation for why this polymorphism has been so heavily researched over the last 15 years. 5-HTTLPR could provide an explanation for why antidepressants seem to have such varying impacts on different people. It suggests that antidepressants are more effective in reducing anxiety or depression in individuals who carry the long allele.

This polymorphism has been in the news recently because of a study conducted in the Netherlands which showed that marijuana had differing effects on people with the short and long alleles in the 5-HTTLPR region. It showed that marijuana was more likely to cause/aggravate symptoms of depression or anxiety among individuals with the short allele.