Journal of Affective Disorders Reports (Dec 2023)
Stress-induced alterations in hippocampal BDNF in the pathophysiology of major depressive disorder and the antidepressant effect of saffron
Abstract
Background: Major depressive disorder affects more than 300 million people worldwide yet the pathophysiology is not fully understood. This review aimed to investigate the mechanistic link between stress-induced alterations in hippocampal BDNF and major depressive disorder, and whether the nutritional intervention Crocus sativus (saffron) could alleviate symptoms. Methods: A three stage systematic literature search was undertaken to identify: (1) review, (2) mechanistic and (3) intervention evidence relevant to the research objectives. 103 peer-reviewed papers published in English met the inclusion criteria. All accepted papers were assessed for quality prior to narrative analysis and synthesis into the results. Results: Animal evidence demonstrates that chronic stress induced a depressive-like phenotype, which was accompanied by significantly reduced hippocampal expression of BDNF. This was corroborated by findings in 5 human case control studies. Preclinical evidence suggests that saffron is able to increase hippocampal levels of BDNF and, in clinical trials, doses of 30mg/day of saffron were significantly more effective than placebo and equally as effective as antidepressant drugs at improving symptoms of depression. Limitations: The mechanistic evidence is largely correlative rather than causal. Larger scale trials are needed to confirm saffron's antidepressant effect before it can be widely recommended as a nutritional intervention for major depressive disorder. Conclusion: Correlative evidence in this review suggests that depleted hippocampal levels of BDNF may play a role in the pathophysiology of major depressive disorder; however, a causal link is yet to be established. Saffron may present an emerging and promising non-pharmaceutical intervention for major depressive disorder.
