Identifying individual differences of fluoxetine response in juvenile rhesus monkeys by metabolite profiling.
Transl Psychiatry
; 4: e478, 2014 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-25369145
ABSTRACT
Fluoxetine is the only psychopharmacological agent approved for depression by the US Food and Drug Administration for children and is commonly used therapeutically in a variety of neurodevelopmental disorders. Therapeutic response shows high individual variability, and severe side effects have been observed. In the current study we set out to identify biomarkers of response to fluoxetine as well as biomarkers that correlate with impulsivity, a measure of reward delay behavior and potential side effect of the drug, in juvenile male rhesus monkeys. The study group was also genotyped for polymorphisms of monoamine oxidase A (MAOA), a gene that has been associated with psychiatric disorders. We used peripheral metabolite profiling of blood and cerebrospinal fluid (CSF) from animals treated daily with fluoxetine or vehicle for one year. Fluoxetine response metabolite profiles and metabolite/reward delay behavior associations were evaluated using multivariate analysis. Our analyses identified a set of plasma and CSF metabolites that distinguish fluoxetine- from vehicle-treated animals and metabolites that correlate with impulsivity. Some metabolites displayed an interaction between fluoxetine and MAOA genotype. The identified metabolite biomarkers belong to pathways that have important functions in central nervous system physiology. Biomarkers of response to fluoxetine in the normally functioning brain of juvenile nonhuman primates may aid in finding predictors of response to treatment in young psychiatric populations and in progress toward the realization of a precision medicine approach in the area of neurodevelopmental disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fluoxetina
/
Inibidores Seletivos de Recaptação de Serotonina
/
Desvalorização pelo Atraso
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Comportamento Impulsivo
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Macaca mulatta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha