RESUMEN
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.
Asunto(s)
Ansiedad/etiología , Hormona Liberadora de Corticotropina/metabolismo , Depresión/etiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Prosencéfalo/metabolismo , Adaptación Ocular/efectos de los fármacos , Adaptación Ocular/genética , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/genética , Conducta Animal/fisiología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Ritmo Circadiano/efectos de los fármacos , Ritmo Circadiano/genética , Hormona Liberadora de Corticotropina/genética , Depresión/tratamiento farmacológico , Depresión/genética , Modelos Animales de Enfermedad , Doxiciclina/administración & dosificación , Embrión de Mamíferos , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/genética , Hormona del Crecimiento/metabolismo , Suspensión Trasera/métodos , Sistema Hipotálamo-Hipofisario/crecimiento & desarrollo , Sistema Hipotálamo-Hipofisario/metabolismo , Imipramina/farmacología , Imipramina/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación/genética , Sistema Hipófiso-Suprarrenal/crecimiento & desarrollo , Sistema Hipófiso-Suprarrenal/metabolismo , Prosencéfalo/embriología , Prosencéfalo/crecimiento & desarrollo , Radioinmunoensayo/métodos , Tiempo de Reacción/genética , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismoRESUMEN
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.
