title: Isovaleric acid in stool correlates with human depression.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Chemistry, Biotechnology and Food Science , Norwegian University of Life Sciences , P.O. Box 5003, 1432 Ås , Norway.
authors.forename: Olga
authors.initials: O
authors.lastname: Szczesniak
authors.affiliation: b Department of Research , Innlandet Hospital Trust , Brumunddal , Norway.|c Hedmark University College , Elverum , Norway.|d Department of Psychology , Norwegian University of Science and Technology , Trondheim , Norway.
authors.forename: Knut A
authors.initials: KA
authors.lastname: Hestad
authors.affiliation: a Department of Chemistry, Biotechnology and Food Science , Norwegian University of Life Sciences , P.O. Box 5003, 1432 Ås , Norway.
authors.forename: Jon Fredrik
authors.initials: JF
authors.lastname: Hanssen
authors.affiliation: a Department of Chemistry, Biotechnology and Food Science , Norwegian University of Life Sciences , P.O. Box 5003, 1432 Ås , Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Rudi
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D000068016:Eubacteriales / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology; D064806:Dysbiosis / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology / Q000523:psychology; D005243:Feces / Q000737:chemistry* / Q000382:microbiology; D005410:Flame Ionization; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D045782:Hemiterpenes; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D058889:Molecular Typing; D009664:Norway; D010421:Pentanoic Acids / Q000032:analysis*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; D006854:Hydrocortisone
keywords: Cortisol; Depression; Isovaleric acid; Microbiota; VFA