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Abstract
Objective: Human depression is a major burden, both on the individuals who suffer from the disease and on society at large. Traditionally, depression has been linked to psychological and biological causes, but there has been increasing interest in the gut–brain axis. In this regard, we have recently shown that specific bacteria are correlated with human depression, and we hypothesize that volatile fatty acids (VFAs) are mediators.
Methods: Here, we analyzed the direct correlation between VFAs, depression and cortisol in a cohort consisting of 34 depressed patients and 17 controls.
Results: We found statistically significant correlations between depression and the VFA isovaleric acid, as well as between isovaleric acid and cortisol. Furthermore, bacteria that previously have been identified as being correlated with depression were also correlated with isovaleric acid. Isovaleric acid showed a bimodal distribution in which the depressed patients were overrepresented in the high level group (P < 0.00005, binominal test).
Discussion: It has recently been shown that gut-derived VFAs can cross the blood–brain barrier, where isovaleric acid interferes with synaptic neurotransmitter release. The multiple correlation patterns, in addition to a potential mechanistic model, point towards a potential causal relationship between depression and isovaleric acid.
Acknowledgements
We wish to thank Michel Brunes Berg of the Norwegian University of Life Sciences for assisting with the VFA analyses, the Hormone Laboratory at Oslo University Hospital, Aker Medical Clinic, which performed all the cortisol measurements, and Connie J. Stultz Government Authorized Translator (Norwegian-English) who proofread the manuscript. The study was supported by funding from Innlandet Hospital Trust, Lillehammer University College, Hedmark University College and the Norwegian University of Life Sciences.
Disclaimer statements
Contributors O.S. performed experiments; K.H. designed study; J.F.H. data interpretation; K.R. data interpretation and wrote the paper.
Funding None.
Conflicts of interest None.
Ethics approval The study has received ethical approval.