Background: The neurotrophic hypothesis of depression postulates that neuronal plasticity is a key factor in the development of depression and in the clinical response to antidepressants. Brain-derived neurotrophic factor (BDNF) is an important protein in this process.
Aim: To provide a survey of the current scientific view regarding the neurotrophic hypothesis of depression.
Method: We studied the literature using PubMed.
Results: The serum bdnf level was found to be consistently lower in depressed patients compared to healthy controls. In short open-label antidepressant treatment trials the bdnf levels were found to be higher post-treatment than pre-treatment. Longitudinal analysis of a large naturalistic cohort study revealed that it was more likely that bdnf serum levels were lower as a result of depression than that they represented an etiological factor for the illness.
Conclusion: These findings show that the neurotrophic hypothesis of depression is more complex than previously assumed. Animal studies have shown a correlation between stress, diminished bdnf expression in the brain and depressive-like behavior. Studies in humans, on the other hand, particularly those with a longitudinal design, suggest that the decrease in serum bdnf is a consequence of the depression rather than vice versa. This is in sharp contrast to the original assumptions of the neurotrophic hypothesis.