RESUMO
BACKGROUND: In the brain, processing of fearful stimuli engages the amygdala, and the variability of its activity is associated with genetic factors as well as with emotional salience. The objective of this study was to explore the relevance of personality style for variability of amygdala response. METHODS: We studied two groups (n=14 in each group) of healthy subjects categorized by contrasting cognitive styles with which they attribute salience to fearful stimuli: so-called phobic prone subjects who exaggerate potential environmental threat versus so-called eating disorders prone subjects who tend to be much less centered around fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T during performance of a perceptual task of threatening stimuli and they were also matched for the genotype of the 5' variable number tandem repeat (VNTR) polymorphism in the serotonin transporter. RESULTS: The fMRI results indicated that phobic prone subjects selectively recruit the amygdala to a larger extent than eating disorders prone subjects. Activity in the amygdala was also independently predicted by personality style and genotype of the serotonin transporter. Moreover, brain activity during a working memory task did not differentiate the two groups. CONCLUSIONS: The results of the present study suggest that aspects of personality style are rooted in biological responses of the fear circuitry associated with processing of environmental information.
Assuntos
Tonsila do Cerebelo/fisiologia , Medo/fisiologia , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Repetições Minissatélites/genética , Proteínas do Tecido Nervoso/genética , Personalidade/fisiologia , Adulto , Tonsila do Cerebelo/irrigação sanguínea , Análise de Variância , Mapeamento Encefálico , Estudos de Coortes , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Feminino , Lateralidade Funcional , Genótipo , Humanos , Processamento de Imagem Assistida por Computador/métodos , Modelos Lineares , Imageamento por Ressonância Magnética/métodos , Masculino , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos/estatística & dados numéricos , Oxigênio/sangue , Personalidade/genética , Transtornos Fóbicos/fisiopatologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
OBJECTIVE: Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia, and both have been associated with dopamine dysregulation and with a functional polymorphism (Val(108/158)Met) in the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation in the prefrontal cortex. The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation, working memory performance, and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug. METHOD: Thirty patients with acute untreated schizophrenia were clinically evaluated with the Positive and Negative Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week prospective study of olanzapine treatment. Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks. RESULTS: There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function. Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment. A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale. CONCLUSIONS: These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.
Assuntos
Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Catecol O-Metiltransferase/genética , Dopamina/metabolismo , Córtex Pré-Frontal/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/farmacologia , Benzodiazepinas/farmacologia , Catecol O-Metiltransferase/metabolismo , Feminino , Genótipo , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/psicologia , Metionina/genética , Testes Neuropsicológicos , Olanzapina , Polimorfismo Genético/genética , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/enzimologia , Estudos Prospectivos , Esquizofrenia/diagnóstico , Resultado do Tratamento , Valina/genéticaRESUMO
BACKGROUND: Earlier cross-sectional studies with functional magnetic resonance imaging (fMRI) in treated patients with schizophrenia have reported abnormalities of cortical motor processing, including reduced lateralization of primary sensory motor cortex. The objective of the present longitudinal study was to evaluate whether such cortical abnormalities represent state or trait phenomena of the disorder. METHODS: Seventeen acutely ill, previously untreated patients were studied after 4 weeks and after 8 weeks of olanzapine therapy. Seventeen matched healthy subjects served as control subjects. All subjects underwent two fMRI scans 4 weeks apart during a visually paced motor task using a simple periodic block design. Functional magnetic resonance imaging data were analyzed in Statistical Parametric Mapping (SPM99). Region of interest analyses were used to determine a laterality quotient (an index of lateralization) of motor cortical regions. RESULTS: The fMRI data indicated that patients had reduced activation of the primary sensory motor cortex at 4 weeks but not at 8 weeks; however, the laterality quotient in the primary sensory motor cortex was reduced in patients at both time points. CONCLUSIONS: These results suggest that some cortical abnormalities during motor processing represent state phenomena, whereas reduced functional lateralization of the primary sensory motor cortex represents an enduring trait of schizophrenia.
