In examining the role played by neurotransmitters in mental illness, many studies have identified serotonin, and the serotonin transporter gene (SLC6A4) specifically, as a crucial influence in depression. A variation of this gene, known as the 5-HTTLPR short variant, affects how much serotonin is available within the brain and can increase an individual's risk of developing depression. In a new study published in the journal Molecular Psychiatry, researchers funded by the National Institute of Mental Health investigated connections between the SLC6A4 gene and the brain-derived neurotrophic factor (BDNF) gene, which has also been implicated in mood disorders. They identified a variation in the BDNF gene that may counter the vulnerability associated the short version of 5-HTTLPR.
The BDNF gene produces proteins that aid in cell growth and survival, and it also acts as a mediator during neurotransmission. In response to serotonin signaling, this gene facilitates changes in the brain that allow neurons to send and receive the neurotransmitter. The BDNF gene, and the MET version of this gene in particular, has been linked to multiple psychiatric conditions, including depression. Researchers have also noted that antidepressants, while working to increase the amount of serotonin in the brain, also lead to an increase in BDNF levels. With this connection in mind, the researchers of this current study focused on the interactions between the short version of 5-HTTLPR and the MET version of the BDNF gene.
The researchers scanned the brains of 111 healthy individuals. None of these subjects had depression, and it is important to note that the study's intention was not to determine whether or not the subjects had developed or would develop depression. Rather, the researchers were interested in seeing if the genetic variations could create molecular modifications known to increase the risk for depression. Interestingly, the brain scans revealed that individuals with the short version of 5-HTTLPR who did not also have the MET variation in the BDNF gene possessed alterations in neural networks that help regulate mood, an indication that they have an increased vulnerability for depression. Individuals carrying both variations, however, did not have these same alterations and appeared not to have a heightened risk for depression.
In many cases it is believed that complex genetic interactions underly depression, and research examining how multiple genes affect each other can provide insight. These findings suggest that when variations in the BDNF and SLC6A4 genes occur together, the molecular alterations linked to SLC6A4, which put individuals at risk for depression, may not be present. Further research is necessary to see if these variations are also associated with differing rates of depression, as the results of this study seem to indicate. Importantly, this study demonstrates how multiple, interconnected factors may contribute to depression. To better understand how depression develops, we need to consider genetic and environmental influences together and take into account the various ways in which these factors interact.
|