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Int J Neuropsychopharmacol ; 18(6)2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25603859

RESUMO

BACKGROUND: According to the current schizophrenia treatment guidelines, 3 levels of responsiveness to antipsychotic medication exist: those who respond to first-line antipsychotics, those with treatment-resistant schizophrenia who respond to clozapine, and those with clozapine-resistant or ultra-treatment resistant schizophrenia. Proton magnetic resonance spectroscopy studies indicate that antipsychotic medication decreases glutamate or total glutamate + glutamine in the brains of patients with schizophrenia and may represent a biomarker of treatment response; however, the 3 levels of treatment responsiveness have not been evaluated. METHODS: Proton magnetic resonance spectroscopy spectra were acquired at 3 Tesla from patients taking a second generation non-clozapine antipsychotic (first-line responders), patients with treatment-resistant schizophrenia taking clozapine, patients with ultra-treatment resistant schizophrenia taking a combination of antipsychotics, and healthy comparison subjects. RESULTS: Group differences in cerebrospinal fluid-corrected total glutamate + glutamine levels scaled to creatine were detected in the dorsolateral prefrontal cortex [df(3,48); F = 3.07, P = .04, partial η(2) = 0.16] and the putamen [df(3,32); F = 2.93, P = .05, partial η(2) = 0.22]. The first-line responder group had higher dorsolateral prefrontal cortex total glutamate + glutamine levels scaled to creatine than those with ultra-treatment resistant schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family-wise error-corrected]. Those with treatment-resistant schizophrenia had higher total glutamate + glutamine levels scaled to creatine in the putamen than the first-line responders (mean difference = 0.31, standard error = 0.12, P = .05, family-wise error-corrected) and those with ultra-treatment-resistant schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family-wise error-corrected). CONCLUSIONS: Total glutamate + glutamine levels scaled to creatine in the putamen may represent a marker of response to clozapine. Future studies should investigate glutamatergic anomalies prior to clozapine initiation and following successful treatment.


Assuntos
Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Clozapina/uso terapêutico , Resistência a Medicamentos , Ácido Glutâmico/líquido cefalorraquidiano , Glutamina/líquido cefalorraquidiano , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Biomarcadores/líquido cefalorraquidiano , Encéfalo/metabolismo , Estudos de Casos e Controles , Creatina/líquido cefalorraquidiano , Quimioterapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Esquizofrenia/líquido cefalorraquidiano , Esquizofrenia/diagnóstico , Resultado do Tratamento , Adulto Jovem
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