Assuntos
Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Mianserina/análogos & derivados , Esquizofrenia/tratamento farmacológico , Adulto , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/uso terapêutico , Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Mianserina/administração & dosagem , Mianserina/uso terapêutico , Mirtazapina , Olanzapina , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Resultado do Tratamento , Adulto JovemRESUMO
RATIONALE: Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. OBJECTIVE: We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). METHODS: Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p < 0.05, family-wise error corrected) was used. RESULTS: On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. CONCLUSIONS: These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.