Although evidence shows that depression has a genetic component, scientists have struggled to identify the genes that contribute to its manifestation. Depression is common, influenced by the environment and life events. It is also complex in that multiple genes interact to cause its symptoms, making it difficult for scientists to point to any causative genes with certainty. The genes that have been associated with the development of depression tend to increase the risk only slightly.
NTRK3
The gene NTRK3 on the long arm of chromosome 15 encodes a receptor that binds to neurotrophin 3, a protein that stimulates nerve growth. Scientists used linkage studies examining regions of shared DNA sequences among family members with depression compared to those without depression to identify NTRK3 as a candidate gene. People with depression were slightly more likely to carry a particular common variant of the NTRK3 gene. Because of the strong potential for false positive results, scientists do not place too much importance on the results of one linkage study. A second team of scientists using a separate group of families also identified NTRK3 as a candidate gene for depression, says Dr. Tanya Golster-Dubner and her colleagues in the 2010 issue of "Israeli Journal of Psychiatry." The replication, along with the fact that the NTRK3 gene product is found in brain regions important for depression, make this gene a promising candidate.
SLC6A4
The gene SLC6A4 lies on the long arm of chromosome 17. It encodes a protein that acts as a chaperone for the neurotransmitter serotonin, an important factor in depression as shown by the serotonin- modulating medications that treat depression. As described by Goltser-Dubner, alterations in the SLC6A4 gene affect its level of expression. Compared to the "long" form of SLC6A4, the "short" form makes less protein, and the "short" form occurred more often in people with depression. The effect of SLC6A4 on depression is quite small, according to Drs. Stanley Shyn and Steven Hamilton in their 2010 paper in "Psychiatric Clinics of North America."
APOE4
The APOE4 gene is probably better known for its role in Alzheimer's disease, but variations in the gene can also influence the risk for developing depression. A particular form or allele of the APOE4 gene provides modest protection against depression. This illustrates the complexity of the genetics of depression, because scientists have to account for the effects of protective genes versus the detrimental effects of susceptibility genes without knowing the identity of most of the genes in either role.
Other
Scientists have identified many other candidate genes for depression, but the results are not proven by replication and the effects are small. Some of the other more promising candidates include MTHFR, GNB3, GRM7 and PCLO. How the products of these genes could influence depression remains unclear.
References
- Dr. Goltser-Dubner, Israeli Journal of Psychiatry and Related Sciences, 2010.
- "Psychiatric Clinic of North America"; Stanley Shyn and Steven Hamilton; The Genetics of Major Depression: Moving Beyond the Monoamine Hypothesis; March 2010.
