Protocolo Unificado de Tratamiento Transdiagnóstico para los Trastornos Emocionales: revisión teórica

Revisión Teórica de las aportaciones recientes en investigación y tratamiento, acerca del Protocolo Unificado para el Tratamiento Transdiagnóstico de los Trastornos Emocionales (PU). El PU surge a partir de las evidencias encontradas acerca de los factores temperamentales que subyacen a los Trastornos Emocionales, entre los que se destaca el Neuroticismo. Surge como un modo de enfocar el tratamiento de estos trastornos hacia los elementos que tienen en común, en lugar de los síntomas específicos que los diferencian. A pesar de que el PU todavía es bastante novedoso, ya existen varias investigaciones acerca del tema, las cuales parecen indicar que el tratamiento es eficaz para la mejora de estos trastornos y sus síntomas. Estas aportaciones son de relevancia desde una perspectiva psicopatológica y clínica, ya que se abren puertas a un nuevo método de tratamiento, que podría aportar beneficios en varias áreas y podría suponer en el futuro un cambio favorable en los tratamientos que existen actualmente para los Trastornos Emocionales

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

International audienc