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Tijdschrift voor Psychiatrie 58 (2016) 3, 215 - 222

Essay

The neurotrophic hypothesis of depression

B.A.A. Bus, M.L. Molendijk

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.

keywords depression, brain-derived neurotrophic factor, neurotrophic hypothesis of depression, antidepressant