Nature working with ‘nurture’: insight into the “depression gene”
Depression is among the world’s most burdensome diseases, and is estimated to become the second leading cause of disease burden by 2020. Depression has been associated to a number of environmental factors, such as childhood abuse and neglect, or stressful events later in life. Genetic make-up has also been considered a vulnerability factor, since not everyone seems to react to stress and develop depressive episodes in the same way.
One of the “depression genes” – serotonin transportergene – has recently received much attention, since evidence suggests that polymorphism linked to the gene (5-HTTLPR) is related to elevated symptoms of depression following stressful experiences and, especially, childhood maltreatment.
The role of serotonin transporter gene in occurrence and persistence of clinical depression has now been established, however, other genes have also been suggested to play a part in stress-triggered depression. A recent study suggests one of them – brain-derived neurotrophic factor(BDNF) gene – could be a major factor in the onset of depression after stressful life events, such as divorce or death in the family.
BDNF protein is involved in the development and survival of neurons, as well as synaptic connectivity within the brain. Stress is thought to reduce BDNF levels in the brain, as such decreasing the function of limbic regions, such as hippocampus, involved in cognition and emotion processing. These changes are thought to manifest in depressive mood, which can be reversed by antidepressants.
A single nucleotide polymorphism (SNP) within BDNF gene is thought to be related to reduced BDNF activity, therefore contributing to genetic vulnerability to mental conditions, including mood disorders and depression. In fact, animal models show that a specific polymorphism of the gene is related to anxiety-related behavior under stress conditions, and a number of studies suggest a link between the SNP in question and impaired stress response.
A meta-analysis compiled data from a number of studies looking at the combined effects of BDNF polymorphism and stress in the development of depression, and found significant interaction between the two factors. Interestingly, childhood adversity only showed a trend towards BDNF-related depression, in contrast to serotonin transporter gene, which interacts significantly with stressful childhood events.
However, influence of other lifetime stressful events on depression seems to be moderated through BDNF polymorphism, emphasizing that predisposition to environment-provoked mental disorders is heritable. Interestingly, research shows that individuals with genetic vulnerability to stress and depression also benefit from positive events or simply lack of stress. Paradoxically, these individuals have significantly reduced likelihood of depression onset, much more so than those without such genetic make-up, providing they experience no severe stress.
Understanding the etiology of depression is crucial, since this disabling disorder takes a toll on individuals and the society. However, it is clear that genetic factors, particularly serotonin transporter and BDNF genes, play distinct roles in stress-induced depression and are related to early and late lifetime events, emphasizing the importance of both environment and inherited sensitivity in the development of the disease.