Table of Contents
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.