Cognition and the five-factor model of the positive and negative syndrome scale in schizophrenia.

Different exploratory and confirmatory factorial analyses of the Positive and Negative Syndrome Scale (PANSS) have found a number of factors other than the original positive, negative, and general psychopathology. Based on a review of previous studies and using confirmatory factor analyses (CFA), Wallwork et al. (Schizophr Res 2012; 137: 246-250) have recently proposed a consensus five-factor structure of the PANSS. This solution includes a cognitive factor which could be a useful measure of cognition in schizophrenia. Our objectives were 1) to study the psychometric properties (factorial structure and reliability) of this consensus five-factor model of the PANSS, and 2) to study the relationship between executive performance assessed using the Wisconsin Card Sorting Test (WCST) and the proposed PANSS consensus cognitive factor (composed by items P2-N5-G11). This cross-sectional study included a final sample of 201 Spanish outpatients diagnosed with schizophrenia. For our first objective, CFA was performed and Cronbach's alphas of the five factors were calculated; for the second objective, sequential linear regression analyses were used. The results of the CFA showed acceptable fit indices (NNFI=0.94, CFI=0.95, RMSEA=0.08). Cronbach's alphas of the five factors were adequate. Regression analyses showed that this five-factor model of the PANSS explained more of the WCST variance than the classical three-factor model. Moreover, higher cognitive factor scores were associated with worse WCST performance. These results supporting its factorial structure and reliability provide robustness to this consensus PANSS five-factor model, and indicate some usefulness of the cognitive factor in the clinical assessment of schizophrenic patients.

[COMT Val158Met polymorphism and schizophrenia in a series of Spanish patients]. / Polimorfismo Val158Met de COMT y esquizofrenia: estudio de asociación en una muestra de pacientes españoles.

BACKGROUND AND OBJECTIVE: Catecol-O-methyl transferase (COMT) enzyme plays a significant role in the regulation of the dopaminergic system in the prefrontal cortex. Several studies have assessed the association between modifications of the COMT activity and schizophrenia, but without consistent results. COMT gene contains a single nucleotide functional polymorphism which produces the change of a valine for a methionine at position 158. The effect of this aminoacid change is a modification of COMT enzymatic activity: valine-COMT displays a significantly higher capacity of postsynaptic dopamine degradation than methionine-COMT. The objective of this study is to carry out a genetic association study of the functional polymorphism Val158Met in a sample of Spanish schizophrenic patients and healthy controls. PATIENTS AND METHOD: This is a case-control study made up of 177 patients and 141 healthy controls. All patients -115 males and 62 females, with ages between 27 and 49 years; mean (standard deviation) of 38 (10.7) years- were being treated in the outpatient Psychiatric Clinic of the Hospital Universitario 12 de Octubre, and fulfilled the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria for schizophrenia (n = 162) or schizoaffective disorder (n = 15). Control subjects -92 males and 49 females, with ages between 26 and 47 years; mean of 36 (9.4) years- were free from medical and psychiatric disorders. Genotype identification was done by means of human genetic molecular techniques coupled to ADN polymerase chain reaction and single strand conformational polymorphism (SSCP) of the COMT Val158Met polymorphism. RESULTS: No statisticaly significant differences were found in the allele frequencies for this polymorphism between patient and control samples. Nevertheless, in genotype analysis and when a model of recessive inheritance (Val/Val vs Val/Met and Met/Met) was assumed, a possible tendency towards statistical significance was observed. Our results do not allow to confirm the possible COMT gene variants contribution to schizophrenia etiopathogenesis, but they offer some evidence which would point to its implication in some patients subgroups. CONCLUSIONS: With the results obtained in this study a possible contribution of the COMT gene in schizophrenia etiopathogenesis cannot be ruled out. The issue of the possible effect of the COMT Val158Met polymorphism in schizophrenia would remain to be open and calls for the need to replicate this kind of studies in greater samples that will allow stratificate analysis by patients subgroups.

Polimorfismo Val158Met de COMT y esquizofrenia: estudio de asociación en una muestra de pacientes españoles / COMT Val158Met polymorphism and schizophrenia in a series of Spanish patients

Fundamento y objetivo: La enzima catecol-O-metiltransferasa (COMT) interviene de un modo significativo en la regulación del sistema dopaminérgico, especialmente en la corteza prefrontal. Estudios previos han evaluado la asociación entre la actividad enzimática de la COMT y la esquizofrenia, aunque los resultados no han sido concluyentes. El gen COMT contiene un polimorfismo funcional que ocasiona, en la posición 158 del péptido, el cambio de valina por metionina y la modificación de la actividad enzimática, de forma que la COMT-valina muestra una capacidad de degradación postsináptica de la dopamina significativamente superior a la COMT-metionina. El objetivo de este trabajo es realizar un estudio de asociación genética con el polimorfismo funcional Val158Met del gen COMT en pacientes con esquizofrenia y en controles sanos españoles. Pacientes y método: Se ha realizado un estudio de casos y controles con una muestra de 177 pacientes y 141 controles. Los pacientes del estudio ­115 varones y 62 mujeres, con una edad entre 27 y 49 años; media (desviación estándar) de 38 (10,7) años­ se incluyeron consecutivamente según acudieron a las consultas del Servicio de Psiquiatría del Hospital Universitario 12 de Octubre y si cumplían criterios DSM-IV (cuarta edición del Diagnostic and Statistical Manual of Mental Disorders) para esquizofrenia (n = 162) o trastorno esquizoafectivo (n = 15). Asimismo, se incluyó a 141 controles evaluados, sanos y libres de enfermedad médica o psiquiátrica ­92 varones y 49 mujeres, con una edad entre 26 y 47 años, media de 36 (9,4) años­. La identificación del genotipo se llevó a cabo por medio de técnicas de genética molecular humana que asociaron la reacción en cadena de la polimerasa del ADN al estudio de la conformación de la hebra simple del ADN (single strand conformational polymorphism; SSCP) del polimorfismo Val158Met de COMT. Resultados: No se encontraron diferencias significativas en las frecuencias de los alelos para este polimorfismo al comparar controles y pacientes. Sin embargo, en el análisis por genotipos y desde un modelo de herencia recesivo (Val/Val frente a Val/Met y Met/Met), se detectó una posible tendencia a la significación. Nuestros resultados no permiten confirmar la posible contribución de variaciones del gen COMT en la etiopatogenia de la esquizofrenia, pero ofrecen indicios que permiten sospechar su participación en algunos grupos concretos de pacientes. Conclusiones: Con los resultados obtenidos en este estudio, la posible contribución del gen COMT en la etiopatogenia de la esquizofrenia no puede descartarse. El debate sobre el posible efecto del polimorfismo Val158Met de COMT en la esquizofrenia se mantendría abierto; de ahí la necesidad de reproducir los estudios en muestras mayores que permitan análisis estratificados de subgrupos de pacientes

Background and objective: Catecol-O-methyl transferase (COMT) enzyme plays a significant role in the regulation of the dopaminergic system in the prefrontal cortex. Several studies have assessed the association between modifications of the COMT activity and schizophrenia, but without consistent results. COMT gene contains a single nucleotide functional polymorphism which produces the change of a valine for a methionine at position 158. The effect of this aminoacid change is a modification of COMT enzymatic activity: valine-COMT displays a significantly higher capacity of postsynaptic dopamine degradation than methionine-COMT. The objective of this study is to carry out a genetic association study of the functional polymorphism Val158Met in a sample of Spanish schizophrenic patients and healthy controls. Patients and method: This is a case-control study made up of 177 patients and 141 healthy controls. All patients ­115 males and 62 females, with ages between 27 and 49 years; mean (standard deviation) of 38 (10.7) years­ were being treated in the outpatient Psychiatric Clinic of the Hospital Universitario 12 de Octubre, and fulfilled the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria for schizophrenia (n = 162) or schizoaffective disorder (n = 15). Control subjects ­92 males and 49 females, with ages between 26 and 47 years; mean of 36 (9.4) years­ were free from medical and psychiatric disorders. Genotype identification was done by means of human genetic molecular techniques coupled to ADN polymerase chain reaction and single strand conformational polymorphism (SSCP) of the COMT Val158Met polymorphism. Results: No statisticaly significant differences were found in the allele frequencies for this polymorphism between patient and control samples. Nevertheless, in genotype analysis and when a model of recessive inheritance (Val/Val vs Val/Met and Met/Met) was assumed, a possible tendency towards statistical significance was observed. Our results do not allow to confirm the possible COMT gene variants contribution to schizophrenia etiopathogenesis, but they offer some evidence which would point to its implication in some patients subgroups. Conclusions: With the results obtained in this study a possible contribution of the COMT gene in schizophrenia etiopathogenesis cannot be ruled out. The issue of the possible effect of the COMT Val158Met polymorphism in schizophrenia would remain to be open and calls for the need to replicate this kind of studies in greater samples that will allow stratificate analysis by patients subgroups