A single administration of the antibiotic, minocycline, reduces fear processing and improves implicit learning in healthy volunteers: analysis of the serum metabolome
Open Access
- 13 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Translational Psychiatry
- Vol. 10 (1), 1-11
- https://doi.org/10.1038/s41398-020-0818-6
Abstract
Minocycline has shown therapeutic promise in pre-clinical animal models and early phase clinical trials for a variety of psychiatric disorders. Previous studies on minocycline have shown its ability to suppress microglia activity and reduce inflammatory cytokine levels, and its amelioration of depressive-like behaviour in animals and humans. However, the underlying mechanisms that lead to minocycline's psychotropic effects are not clear. In this study, we investigated the psychological and biochemical effects of an acute dose of minocycline or placebo in 40 healthy adult volunteers. Psychological changes in emotional processing, implicit learning, and working memory were assessed. Plasma inflammatory markers, measured with enzyme-linked immunosorbent assays, and serum metabolites, measured with proton nuclear magnetic resonance combined with multi-variate analysis techniques, were also studied. Results showed that minocycline administration decreased fear misclassification and increased contextual learning, which suggested that reducing negative biases and improving cognition, respectively, may underlie the antidepressant actions of this agent. An examination of serum metabolites revealed higher levels of lipoproteins, particularly cholesterol, in the minocycline group. Minocycline also decreased circulating concentrations of the inflammatory marker C-Reactive Peptide, which is consistent with previous research. These effects highlight two important psychological mechanisms that may be relevant to the efficacy of minocycline reported in clinical trials, and also suggest a possible largely unexplored lipid-related biochemical pathway for the action of this drug.This publication has 56 references indexed in Scilit:
- Contextual Social Cognition Impairments in Schizophrenia and Bipolar DisorderPLOS ONE, 2013
- HMDB 3.0—The Human Metabolome Database in 2013Nucleic Acids Research, 2012
- Minocycline as adjunctive therapy for patients with unipolar psychotic depression: An open-label studyProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2012
- Using an experimental medicine model to understand the antidepressant potential of the N-Methyl-D-aspartic acid (NMDA) receptor antagonist memantineJournal of Psychopharmacology, 2012
- Treatment-resistant depression: therapeutic trends, challenges, and future directionsPatient Preference and Adherence, 2012
- A cognitive neuropsychological model of antidepressant drug actionProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2011
- Association between Depression and C-Reactive ProteinCardiology Research and Practice, 2011
- Metabolite characterization in serum samples from normal healthy human subjects by 1H and 13C NMR spectroscopyBulletin of the Chemical Society of Ethiopia, 2009
- Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in miceMolecular Psychiatry, 2008
- Toward a Neuropsychological Theory of Antidepressant Drug Action: Increase in Positive Emotional Bias After Potentiation of Norepinephrine ActivityAmerican Journal of Psychiatry, 2003