RESUMO
During development, early-life stress, such as abuse or trauma, induces long-lasting changes that are linked to adult anxiety and depressive behavior. It has been postulated that altered expression of corticotropin-releasing hormone (CRH) can at least partially account for the various effects of stress on behavior. In accord with this hypothesis, evidence from pharmacological and genetic studies has indicated the capacity of differing levels of CRH activity in different brain areas to produce behavioral changes. Furthermore, stress during early life or adulthood causes an increase in CRH release in a variety of neural sites. To evaluate the temporal and spatial specificity of the effect of early-life CRH exposure on adult behavior, the tetracycline-off system was used to produce mice with forebrain-restricted inducible expression of CRH. After transient elevation of CRH during development only, behavioral testing in adult mice revealed a persistent anxiogenic and despair-like phenotype. These behavioral changes were not associated with alterations in adult circadian or stress-induced corticosterone release but were associated with changes in CRH receptor type 1 expression. Furthermore, the despair-like changes were normalized with antidepressant treatment. Overall, these studies suggest that forebrain-restricted CRH signaling during development can permanently alter stress adaptation leading to increases in maladaptive behavior in adulthood.
Assuntos
Ansiedade/etiologia , Hormônio Liberador da Corticotropina/metabolismo , Depressão/etiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Prosencéfalo/metabolismo , Adaptação Ocular/efeitos dos fármacos , Adaptação Ocular/genética , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/genética , Comportamento Animal/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/genética , Hormônio Liberador da Corticotropina/genética , Depressão/tratamento farmacológico , Depressão/genética , Modelos Animais de Doenças , Doxiciclina/administração & dosagem , Embrião de Mamíferos , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Hormônio do Crescimento/metabolismo , Elevação dos Membros Posteriores/métodos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Imipramina/farmacologia , Imipramina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética , Sistema Hipófise-Suprarrenal/crescimento & desenvolvimento , Sistema Hipófise-Suprarrenal/metabolismo , Prosencéfalo/embriologia , Prosencéfalo/crescimento & desenvolvimento , Radioimunoensaio/métodos , Tempo de Reação/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismoRESUMO
Disasters pose a very real threat to every individual in the United States. One way to mitigate the threat of disasters is through personal preparedness, yet numerous studies indicate that individual Americans are not prepared for a disaster. This study attempted to identify the factors most likely to predict individual disaster preparedness. We used 2006 Behavioral Risk Factor Surveillance System (BRFSS) data from the 5 states that included the optional general preparedness module. Respondents were defined as being "prepared" if they were deficient in no more than 1 of the 6 actionable preparedness measures included on the BRFSS. Analyses were conducted comparing preparedness rates based on medical and demographic factors. Using logistic regression, a predictive model was constructed to identify which factors most strongly predicted an individual's likelihood of being prepared. Although 78% of respondents reported feeling prepared for a disaster, just 45% of respondents were actually prepared by objective measures. Factors predicting an increased likelihood of preparedness included feeling "well prepared" (OR 9.417), having a disability or health condition requiring special equipment (OR 1.298), being 55 to 64 years old (OR 1.794), and having an annual income above $50,000 (OR 1.286). Among racial and ethnic minorities, an inability to afford medical care in the previous year (OR .581) was an important factor in predicting a decreased likelihood of being prepared. This study revealed a pervasive lack of disaster preparedness overall and a substantial gap between perceived and objective preparedness. Income and age were important predictors of disaster preparedness.
