Abstract
Schizophrenia and autism spectrum disorder have long been associated with elevated levels of various small phenolic molecules (SPMs). In turn, the gut microbiota (GMB) has been implicated in the kinetics of many of these analytes. Unfortunately, research into the possible relevance of GMB-mediated SPMs to neuropsychiatry continues to be limited by heterogeneous study design, numerous sources of variance and technical challenges. Some SPMs have multiple structural isomers and most have conjugates. Without specialized approaches, SPMs can be incorrectly assigned or inaccurately quantified. In addition, SPM levels can be affected by dietary polyphenol or protein consumption and by various medications and diseases. Nonetheless, heterotypical excretion of various SPMs in association with schizophrenia or autism continues to be reported in independent samples. Recent studies in human cerebrospinal fluid demonstrate the presence of many SPMs A large number of these are bioactive in experimental models. Whether such mechanisms are relevant to the human brain in health or disease is not known. Systematic metabolomic and microbiome studies of well-characterized populations, an appreciation of multiple confounds, and implementation of standardized approaches across platforms and sites are needed to delineate the potential utility of the phenolic interactome in neuropsychiatry.
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Abbreviations
- 2-HCA :
-
2-hydroxycinnamic acid
- 2-HPAA:
-
2-hydroxyphenylacetic acid
- 2,3-DHHCA:
-
2,3-dihydroxyhydrocinnamic acid
- 2,4-DHHCA:
-
2,4-dihydroxyhydrocinnamic acid
- 2,4-HPPA :
-
2-(4-hydroxyphenyl)propanoic acid
- 3-PPA:
-
3-phenylpropionic acid
- 3-HHA:
-
3-hydroxyhippuric acid
- 3-HBA:
-
3-hydroxybenzoic acid
- 3-HCA:
-
3-hydroxycinnamic acid
- 3-HHA :
-
3-hydroxyhippuric acid
- 3-HPAA :
-
3-hydroxyphenylacetic acid
- 3,2-HPPA:
-
3-(2-hydroxyphenyl) propionic acid
- 3,3-HPHPA:
-
3-hydroxy-3-(3-hydroxyphenyl)propanoic acid
- 3,3-HPPA :
-
3-(3-hydroxyphenyl) propionic acid
- 3,4-DHCA:
-
3,4-dhydroxycinnamic acid
- 3,4-DHHCA:
-
3,4-dihydroxyhydrocinnamic acid
- 3,4-DOPAC:
-
3,4-dihydroxyphenylacetic acid
- 3,4-HMPHA:
-
3-(3-hydroxy-4-methoxyphenyl) hydracrylic acid
- 3,4-HPPA:
-
3-(4-hydroxyphenyl) propionic acid
- 3,5-DHHCA:
-
3,5-dihydroxyhydrocinnamic acid
- 4-HHA:
-
4-hydroxyhippuric acid
- 4-HBA:
-
4-hydroxybenzoic acid
- 4-HCA:
-
4-hydroxycinnamic acid
- 4-HPAA:
-
4-hydroxyphenylacetic acid
- 4-HPLA:
-
4-hydroxyphenyllactic acid
- 4-HPPU:
-
4-hydroxyphenylpyruvic acid
- BA:
-
Benzoic acid
- FA:
-
Ferulic acid
- HA:
-
Hippuric acid
- HMA:
-
Hydroxymandelic acid
- HVA:
-
Homovanillic acid
- L-PHE:
-
l-Phenylalanine
- L-TYR:
-
l-Tyrosine
- PAA:
-
Phenylacetic acid
- PPG:
-
Phenylpropionylglycine
- VMA:
-
Vanillylmandelic acid
- ADOS:
-
Autism Diagnostic Observation Scale
- APD:
-
Antipsychotic drug
- BBB:
-
Blood brain barrier
- BPD:
-
Bipolar disorder
- CSF:
-
Cerebrospinal fluid
- DSM:
-
Diagnostic and Statistical Manual
- FEP:
-
First episode psychosis
- GMB:
-
Gut microbiota
- HR:
-
High risk
- ICD:
-
International Classification of Diseases
- LC:
-
Liquid chromatography
- MS:
-
Mass spectrometry
- np:
-
Not provided
- NSIB:
-
Neurotypical siblings
- nsd:
-
Not significantly different
- PDD:
-
Pervasive developmental disorder
- PSE:
-
Present state examination
- quaL:
-
Qualitative
- quaN:
-
Quantitative
- RDC:
-
Research Diagnostic Criteria
- RIS:
-
Risperidone
- SGA:
-
Second-generation antipsychotic
- SPM:
-
Small phenolic molecule
- UC:
-
Unrelated control
- UHR:
-
Ultra high risk
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This works was supported by the Louis Stokes Cleveland DVAMC Research Service and by a grant from the VISN 10 Research Initiative Program (to CJD and GEJ).
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Jaskiw, G.E., Obrenovich, M.E. & Donskey, C.J. The phenolic interactome and gut microbiota: opportunities and challenges in developing applications for schizophrenia and autism. Psychopharmacology 236, 1471–1489 (2019). https://doi.org/10.1007/s00213-019-05267-3
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DOI: https://doi.org/10.1007/s00213-019-05267-3