Olga Szczesniak1, Knut A Hestad2,3,4, Jon Fredrik Hanssen1, Knut Rudi1. 1. a Department of Chemistry, Biotechnology and Food Science , Norwegian University of Life Sciences , P.O. Box 5003, 1432 Ås , Norway. 2. b Department of Research , Innlandet Hospital Trust , Brumunddal , Norway. 3. c Hedmark University College , Elverum , Norway. 4. d Department of Psychology , Norwegian University of Science and Technology , Trondheim , Norway.
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.
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 depressedpatients 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 depressedpatients 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.