Publication: Modelo de interacción gen-ambiente del rendimiento cognitivo en primeros episodios psicóticos
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2017-06-15
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Universidad Complutense de Madrid
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Abstract
Las psicosis constituyen un grupo de trastornos mentales caracterizados por la afectación de las dimensiones clínicas “positiva” (ej. delirios, alucinaciones), “negativa” (ej. abulia, apatía), “afectiva” (ej. depresión) y “cognitiva” (ej. atención, función ejecutiva) (van Os y Kapur, 2009). La afectación cognitiva se relaciona con peor pronóstico funcional (Green et al., 2000) y puede detectarse desde las primeras etapas del trastorno (en casos de primeros episodios psicóticos [PEP]) e incluso en poblaciones de alto riesgo (Valli et al., 2012). Los dominios cognitivos más frecuentemente afectados son atención, velocidad de procesamiento, memoria verbal, memoria de trabajo, función ejecutiva y cognición social (Green et al., 2004). La afectación cognitiva, como las demás dimensiones sintomáticas, está causada y modulada por la interacción de factores genéticos y ambientales (Bilder et al., 2004). Entre los factores genéticos moduladores de la gravedad del déficit cognitivo destaca el polimorfismo Val158Met del gen COMT (con tres variantes genotípicas: Val/Val, Val/Met, Met/Met; los sujetos portadores Val tienden a presentar peor rendimiento cognitivo que los Met/Met) (Ira et al., 2013). Los factores ambientales implicados en la aparición y gravedad de la afectación cognitiva actúan mediante la interferencia de procesos del neurodesarrollo. Entre estos factores se ha estudiado el papel de las complicaciones obstétricas (CO) y del estatus socioeconómico (ESE) parental, que juegan un papel importante en los PEP (Cannon et al., 2002c; Kwok, 2014). Sin embargo, no hay estudios que evalúen la influencia de la interacción entre el polimorfismo Val158Met del gen COMT, las CO y el ESE parental sobre el rendimiento cognitivo en pacientes con PEP. Por ello, esta tesis tiene como objetivo principal estudiar el efecto modulador del polimorfismo Val158Met del gen COMT sobre la influencia de los factores ambientales CO y ESE parental en la respuesta conjunta en pacientes PEP y controles sanos. La hipótesis principal es que los sujetos portadores Val con CO y/o bajo ESE parental tendrán un peor rendimiento cognitivo que los portadores Val sin ningún factor ambiental y que los sujetos Met/Met; este efecto aparecerá en controles y pacientes, pero de forma más acusada en pacientes...
Psychotic disorders are characterized by four symptomatic dimensions, namely, positive (e.g. delusions and hallucinations), negative (e.g. apathy, lack of interest), affective (e.g. depression), and cognitive (e.g. attention, executive function) (van Os y Kapur, 2009). Cognitive deficit is related to worse functional prognosis (Green et al., 2000) and can be detected during the early stages (in first-episode psychosis [FEP]) and in high-risk populations (Valli et al., 2012). The most frequently affected cognitive domains are attention, processing speed, verbal memory, working memory, executive function, and social cognition (Green et al., 2004). Cognitive deficit and the other symptomatic dimensions are caused and mediated by the interaction between genetic and environmental factors (Bilder et al., 2004). Within the genetic factors that modulate the severity of cognitive deficit, the COMT gene is an accepted candidate gene for schizophrenia and other psychoses because of its position (located in a fragment of chromosome 22q11) and because it encodes a key dopamine catabolic enzyme (Sagud et al., 2010). The polymorphism Val158Met of the COMT gene is the functional polymorphism responsible for three genotypes, namely, Val/Val, Val/Met, and Met/Met. Carriers of Val tend to present worse cognitive performance than Met/Met (Ira et al., 2013). The environmental factors involved in the onset and severity of the cognitive deficit act through interference with neurodevelopmental processes. These factors include obstetric complications (OC) and parental socioeconomic status (SES), which are thought to play a key role in FEP (Cannon et al., 2002c; Kwok, 2014). No studies have evaluated the effect of the interaction between COMT Val158Met polymorphism, OC, and parental SES on cognitive performance in patients with FEP. Therefore, the main objective of the present dissertation was to examine whether the effects of the environmental factors OC and low parental SES on cognition were modulated by the COMT Val158Met polymorphism in patients with FEP and healthy controls...
Psychotic disorders are characterized by four symptomatic dimensions, namely, positive (e.g. delusions and hallucinations), negative (e.g. apathy, lack of interest), affective (e.g. depression), and cognitive (e.g. attention, executive function) (van Os y Kapur, 2009). Cognitive deficit is related to worse functional prognosis (Green et al., 2000) and can be detected during the early stages (in first-episode psychosis [FEP]) and in high-risk populations (Valli et al., 2012). The most frequently affected cognitive domains are attention, processing speed, verbal memory, working memory, executive function, and social cognition (Green et al., 2004). Cognitive deficit and the other symptomatic dimensions are caused and mediated by the interaction between genetic and environmental factors (Bilder et al., 2004). Within the genetic factors that modulate the severity of cognitive deficit, the COMT gene is an accepted candidate gene for schizophrenia and other psychoses because of its position (located in a fragment of chromosome 22q11) and because it encodes a key dopamine catabolic enzyme (Sagud et al., 2010). The polymorphism Val158Met of the COMT gene is the functional polymorphism responsible for three genotypes, namely, Val/Val, Val/Met, and Met/Met. Carriers of Val tend to present worse cognitive performance than Met/Met (Ira et al., 2013). The environmental factors involved in the onset and severity of the cognitive deficit act through interference with neurodevelopmental processes. These factors include obstetric complications (OC) and parental socioeconomic status (SES), which are thought to play a key role in FEP (Cannon et al., 2002c; Kwok, 2014). No studies have evaluated the effect of the interaction between COMT Val158Met polymorphism, OC, and parental SES on cognitive performance in patients with FEP. Therefore, the main objective of the present dissertation was to examine whether the effects of the environmental factors OC and low parental SES on cognition were modulated by the COMT Val158Met polymorphism in patients with FEP and healthy controls...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Psicología, leída el 15/12/2016