Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD.
Compared to the accepted rate of progression of non-dysplastic Barrett's to high-grade dysplasia or cancer of 1.0% per patient year, anti-reflux surgery reduces this rate during long-term follow-up. The rate of progression was significantly lower in patients with an intact compared to a disrupted fundoplication, further suggesting that anti-reflux surgery can alter the natural history of Barrett's esophagus.
El uso de antipsicóticos atípicos como terapia adjunta a antidepresivos en el tratamiento del trastorno depresivo mayor (TDM) no psicótico fue práctica común por un largo periodo antes de que los ensayos clínicos a doble-ciego, controlados (con placebo) y al azar, llevados a cabo a gran escala, demostraran su eficacia. El presente estudio se propuso evaluar la frecuencia con la cual pacientes diagnosticados con TDM recibieron tratamiento con agentes antipsicóticos (AP) y examinar los efectos de edad, raza y etnicidad sobre el tipo y dosis de los anti-psicóticos prescritos a una cohorte de pacientes antes de la reciente aprobación de aripiprazole por la Administración de Alimentos y Drogas (FDA), como medicación adjunta para el manejo de esta entidad clínica. Se analizaron las historias clínicas de 1537 pacientes portadores del diagnóstico de depresión unipolar. 1376 presentaron depresión no psicótica y de ellos, 466 (33,9%) recibieron antipsicóticos con predominio de pacientes varones (hombres vs. mujeres: 41,7% vs. 27,8%. z=2,4, p<0,02; odds ratio (OR)=1,97, con error estándar (SE) de 0,57) de origen Hispánico (X2 = 35,8, df = 1, p < 0,0001). Quetiapina fue el antipsicótico más comúnmente prescrito (n=209, 44,8%) con una dosis promedio (±SEM) de 195,1±13,1 mg. Nuestros resultados confirman reportes previos del uso de antipsicóticos (específicamente quetiapina) en la práctica clínica habitual, como tratamiento adjunto en pacientes no psicóticos con diagnóstico de depresión unipolar. Se requiere investigación adicional que indague los efectos a largo plazo de este tipo de medicación en pacientes sin un diagnóstico de trastorno psicótico primario.
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