The Role of DNA Methylation in Regulation of BDNF and Depression Neuropathophysiology


In December 2019, COVID-19 swept across the world, which resulted in a worldwide mandated lock- down and a surge of depression. Depression symptoms may include fatigue, appetite changes, insomnia, poor concentration, anhedonia, and suicide contemplation. At first, depression was thought to arise due to a lack of monoamines, such as dopamine and serotonin, and thus the 'monoamine hypothesis' was created. Unfortunately, scientists quickly discovered this was outdated and created the 'neurotrophin hypothesis'. This hypothesis explained that when facing stressors, neurotrophin levels decreased and a person's vulnerability to depression increased. Neurotrophins are vital for neurogenesis and their decrease can lead to dysfunctional neurogenesis in brain regions responsible for emotion and cognition, such as the hippocampus. While neurogenesis is extremely crucial throughout embryonic and foetal development, the mechanism actually never stops. A neurotrophin that stood out was brain-derived neurotrophic factor (BDNF). Through several studies, it was understood that stressors could increase DNA methylation of BDNF, which reduced BDNF expression. Reduced expression meant that there was a lower concentration of peripheral BDNF and thus, the likelihood of developing depression is higher. In addition, the val66met BDNF genotype could also increase susceptibility to depression. The current research sheds light on how intricately DNA methylation of BDNF is involved in depression neuropathophysiology and that its status may be a suitable biomarker for subtypes of depression.





Publication date

August 2021


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