Metabonomics and Metabolomics

Grainger, David J.; Nicholson, Jeremy K.

doi:10.1002/3527600906.mcb.200400114

Cited by 2 publications

(1 citation statement)

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“… 16 , 17 , 18 Metabolomics is a relatively new technique that analyses the complete collection of metabolites produced by an organism and gives a more dynamic profile compared with proteomics or genomics. 19 The technique has been applied to white and grey matter postmortem brain tissue in schizophrenia and showed an imbalance in metabolites involved in both glucose and oxidative stress functions in mitochondria in individuals with schizophrenia. 20 The investigators found the same dysregulations in the cerebrospinal fluid of prodromal and early psychosis patients 21 , 22 and in peripheral blood of patients with schizophrenia, 23 suggesting that the analysis of non-cerebral biological samples can inform brain states related to schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission

et al. 2015

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Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders.

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