Información del artículo Ambiente familiar y emoción expresada en pacientes con esquizofrenia u o... more Información del artículo Ambiente familiar y emoción expresada en pacientes con esquizofrenia u otras psicosis y en sus familiares de primer grado.
La satisfacción de los profesionales de la medicina es una preocupación en el sector sanitario y ... more La satisfacción de los profesionales de la medicina es una preocupación en el sector sanitario y su medida requiere un cuestionario multidimensional en español que estudie sus necesidades de alto nivel. Los objetivos de este estudio son adaptar el cuestionario 4Cor-nerSAT para la medida de la satisfacción profesional del personal médico y evaluar su validez en nuestro contexto. Método: Se adaptó el cuestionario al español, validándolo en profesionales médicos de hospitales de Andalucía, España. Se realizó un análisis factorial confirmatorio (AFC) para corroborar el modelo a priori y se evaluó la consistencia interna y la validez de constructo mediante el alfa de Cronbach y la correlación entre la escala y el ítem global, respectivamente. Resultados: El cuestionario adaptado se administró a 121 especialistas. El AFC corroboró las cuatro dimensiones del cuestionario (χ2=114,64, df=94, p<0,07; χ2/df=1,22; RMSEA=0,04). La consistencia interna obtuvo un α=0,92 y la correlación entre la suma de la escala y el ítem global verificó la validez de constructo(r=0,77; p<0,001). Conclusiones: Se adaptó al español el cuestionario 4CornerSAT, evidenciado una adecuada validez de constructo y consistencia interna.
Aims: From a dimensional point of view, the schizotypal features would be continuously distribute... more Aims: From a dimensional point of view, the schizotypal features would be continuously distributed in normal population and individuals with schizophrenia spectrum disorders. in the latter, differences have been found in personality traits between the diagnostic categories of the dimension, and also different schizotypy scores between them. in this study our main objective was to specify the domains and traits of pathological personality that can be considered risk factors for schizotypy. Method: SPQ and DAPP-BQ were administered to a sample of 91 subjects that were divided in four groups: psychotic patients with schizophrenia spectrum disorders, siblings of patients from this spectrum, patients with personality disorders, and healthy controls. Results: Patients with personality disorders presented the highest scores of schizotypy measured with SPQ, followed by psychotic patients, siblings, and finally the healthy controls. both groups of patients obtained higher pathological personality scores compared to siblings and controls. in the psychotic patients and their siblings emotional dysregulation, dissocial behavior and inhibition domains correlated with the SPQ factors, while in the personality disorder patients SPQ correlated only with inhibition. the trait social avoidance appears to be a predictive variable of psychometric schizotypy. Conclusions: Pathological personality underlying the schizotypy of psychotic patients of schizophrenia spectrum and their siblings is different from that of the personality disorder group. Social avoidance is a risk factor for schizotypy measured with SPQ.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2005
It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydr... more It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are risk factors for schizophrenia. We conducted a case-control study to investigate whether tHcy levels and MTHFR C677T and A1298C variants are associated with schizophrenia, giving special consideration to confounding factors. Logistic regression analysis showed that neither tHcy nor MTHFR polymorphisms were associated with schizophrenia. Homozygosity for MTHFR C677T was associated with higher tHcy concentrations in control and schizophrenia groups ( P < 0.01), which was mainly driven by the male group. The A1298C variant did not show any association with tHcy concentrations. In conclusion, these results do not confirm an independent relationship of tHcy and MTHFR genotype with risk of schizophrenia. D
Introduction: Impaired sustained and selective attention have been seen as vulnerability factors ... more Introduction: Impaired sustained and selective attention have been seen as vulnerability factors to psychotic disorders. Relatives of psychotic patients are a risk population for psychosis, and previous studies have shown that they displayed more attentional deficits compared with healthy controls. Additionally, relatives have more pathological personality and schizotypy, the least considered also to be the expression of the genetic vulnerability to schizophrenia. There are few studies that relate attention to personality factors in relatives of psychotic patients. Aims: To compare attentional performance of siblings of psychotic patients with those of healthy controls, taking into account their pathological and schizotypal personality. Methods: The Spanish version of the SPQ and the DAPP-BQ were administered to a sample of 51 subjects that were divided into four groups by a hierarchical cluster analysis: siblings with high pathological personality (SHPP), siblings with low pathological personality (SLPP), controls with high pathological personality (CHPP), and controls with low pathological personality (CLPP). In all the subjects we assessed a sustained attention index (SUA) and a selective attention index (SEA). We compared the performance of the four groups on these attentional indexes. Results: We found that SHPP had worse performance on sustained attention compared with CLPP. Specifically this difference was in the reaction time item of the SUA. Conclusions: The high schizotypy and pathological personality had an influence on sustained attentional performance in the siblings of patients with psychosis, but not in the healthy controls.
Objectives: There are few quality-of-life instruments specifically for schizophrenia; thus, the o... more Objectives: There are few quality-of-life instruments specifically for schizophrenia; thus, the objective of our study is to adapt and validate the Satisfaction with Life Domains Scale (SLDS) by Baker and Intagliata. Method: This is a validation study in which the subjects were evaluated on 2 occasions (24-48 hours). The sample is composed of people with schizophrenia from 18 to 65 years old and who were seen in one of the following centers: Sant Joan de Déu-SSM, Hospital Clínic, Hospital de Mataró and Hospital Pere Mata. The SLDS was administered, along with Positive and Negative Syndrome Scale, the Clinical General Impression for Schizophrenia, Global Assessment of Function, Disability Assessment Scale-short version, Beck Cognitive Insight, and the Strauss and Carpenter Prognostic Scale. The Cronbach α test was carried out, and the intraclass correlation coefficient was used to assess test-retest reliability, along with Pearson correlations for discriminating validity. Results: The intraclass correlation coefficients oscillated between 0.51 and 0.83. The SLDS did correlate with any of the other instruments with the exception of the Positive and Negative Syndrome Scale general subscale and the Strauss and Carpenter prognostic scale. Conclusions: The Spanish version of the SLDS was shown to be valid and reliable and provides a fast and specific measure for schizophrenia.
IntroductionThe aim of this study was to validate the Spanish version of the Strauss and Carpente... more IntroductionThe aim of this study was to validate the Spanish version of the Strauss and Carpenter Prognostic Scale for Schizophrenia (Strauss and Carpenter, 1977).
Evidence suggests that myelin alterations could predispose to schizophrenia. Reduced expression o... more Evidence suggests that myelin alterations could predispose to schizophrenia. Reduced expression of several myelin genes has been observed in schizophrenia patients. Recently, we identified the discoidin domain receptor 1 (DDR1; located at human chromosome 6p21.3) as a myelin gene in the mouse model and in a human oligodendroglial cell line. In the present study we screened for single nucleotide polymorphisms (SNPs) in the DNA from 100 schizophrenia patients. We identified a novel mutation within exon 10 that produces the amino-acid substitution N502S in the a-d isoforms, and M475V in the e isoform. However the frequency of the mutation (2%) was similar in schizophrenia patients and in control subjects. In a casecontrol assessment with 389 schizophrenic patients and 615 controls, we identified one SNP (SNP9, rs1049623) associated with schizophrenia (odds ratio = 1.44, 95% confidence interval: 1.15-1.79, adjusted P = 0.0016). This association was confirmed in haplotype analysis; the SNPs 9-10-11 (rs1049623, rs2267641 and rs2239518) haplotype remaining significant even after adjustment for multiple testing (adjusted P = 0.0136). Of note was a strong gender dependence in the association, that is, statistical significance restricted to men (adjusted P-value = 0.0002). Regression analysis of DDR1 mRNA expression in peripheral blood lymphocytes from schizophrenia patients showed that the presence of the G allele significantly decreased the relative number of mRNA copies in a dose-dependent manner (P = 0.003). These data suggest that the risk haplotype tags a cis-acting variant involved in the transcription regulation system of the gene. In conclusion, we propose the DDR1 as a new susceptibility gene for schizophrenia.
The ⑀4 allele of APOE is generally accepted to be a risk factor in Alzheimer's disease and it has... more The ⑀4 allele of APOE is generally accepted to be a risk factor in Alzheimer's disease and it has been related to other neuropsychiatric disorders, including schizophrenia. The results of several case-control studies have been inconclusive. To shed more light on this issue we carried out an association study that compared the APOE common variant in a group of 365 schizophrenia patients and 584 controls. We found no differences in the genotype distributions and allele frequencies of patients and controls. In the group of patients, we also analysed the possible influence of the ⑀4 allele in the clinical variables. The most important findings are that the age at onset (AAO) of ⑀4+ schizophrenic women, those that have one or two ⑀4 alleles, is 4 years earlier than that of ⑀4− women and their risk of suffering a negative syndrome subtype is four times greater. This was not found in schizophrenic men. Our results show that the APOE variant is not a risk factor for developing schizophrenia but that it may modulate its phenotypic expression in a sex-dependent manner. Molecular Psychiatry (2001) 6, 307-310.
Schizotypy has been proposed to be the expression of the genetic vulnerability to schizophrenia. ... more Schizotypy has been proposed to be the expression of the genetic vulnerability to schizophrenia. Schizotypal features have been associated with personality dimensions found in patients with psychosis. In this study, we compared the Dimensional Assessment of Personality Pathology - Basic Questionnaire (DAPP-BQ) scores of patients with psychosis, siblings scoring higher on schizotypy (SSHS), and siblings scoring lower (SSLS). The SSHSs displayed a DAPP-BQ profile characterized by high scores in the dimensions of affective lability, anxiousness, submissiveness, social avoidance, identity problems, oppositionality, narcissism, and restricted expression, distinguishing them from the SSLS. Due to these dimensions, SSHSs are more similar to the patients&amp;amp;amp;amp;amp;amp;amp;amp;#39; DAPP-BQ profile. The results suggest that this pathological personality profile might contribute to increase the risk of developing psychosis in siblings who have more schizotypal features.
Background: Genome-wide association studies using several hundred thousand anonymous markers pres... more Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs).
Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associa... more Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
Wolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode... more Wolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode and characterized by the presence of diabetes mellitus and optic atrophy. Patients and heterozygote carriers are at an increased risk of suffering psychiatric disorders. Mutations in the Wolfram gene (WFS1 ) (4p16.1) are responsible for the development of the disease, and mRNA and protein expression of WFS1 have recently been found in areas of the rat brain that can be related to the psychiatric symptoms. To test the hypothesis that WFS1 mutations in heterozygote carriers or other variants of WFS1 can predispose to mental illness. Stage 1: Exons 2, 4 and 8 of that harbour mutations in Spanish Wolfram syndrome families were examined by Single Strand Conformation Polymorphism and sequencing analysis in 43 patients with affective disorder to identify variants and mutations. Stage 2: two variants identified in stage 1 were analysed in 152 psychiatric patients (118 schizophrenia and 34 affective disorder) and 177 control subjects. Six variants (I333V Ile--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;Val, F341, N500, R708, K774, K811) and a WFS1 mutation (R818C, Arg--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;Cys) were found in the 43 patients analysed in stage 1 of the study. In stage 2, the R818C mutation was not found in the group of psychiatric patients but it was present in one control subject. The association study conducted with the I333V variant did not find significant differences in allele or genotype frequencies between patients and control subjects. Our results suggest that WFS1 is not a major susceptibility gene for the development of psychiatric disorders in our population.
Polyphenols and obesity related pathologies View project Accelerated geroncogenesis: a new experi... more Polyphenols and obesity related pathologies View project Accelerated geroncogenesis: a new experimental framework for modeling and verifying aging-driven alterations in cancer-promoting metabolites View project
The methionine/valine polymorphism at position 129 in the prion protein gene, PRNP M129V, is a kn... more The methionine/valine polymorphism at position 129 in the prion protein gene, PRNP M129V, is a known risk factor for Creutzfeldt-Jakob disease (CJD). Psychiatric manifestations including psychosis are common in the early phase of CJD and it has therefore been hypothesized that the prion protein could be involved in psychotic disorders. Moreover, among the various hypothesized functions of the prion protein, a role in synaptic activity has been described. We have studied the PRNP M129V variant with regard to psychotic disorders from two perspectives: first as a genetic risk factor and second as a genetic factor influencing phenotypic variation. A case-control study of 482 psychotic patients and 502 controls indicated that differences between patients and controls were not present in genotype distributions or allele frequencies. We also studied the influence of this variant in psychopathological symptomatology and neuropsychological performance in a subgroup of 159 psychotic patients. In our sample, patients homozygous for valine at this position presented less severe scores in the general psychopathological subscale (p=0.003) and in the sum of the total items (p=0.007) of the Positive and Negative Syndrome Scale (PANSS). Also, homozygote VV patients presented better scores in most neuropsychological tests, the most significant result of which was for delayed visual memory (p=0.021). In summary, our results do not support the hypothesis that M129V is a susceptibility factor for psychotic disorders. However, it could influence their phenotypic variation at the psychopathological and neuropsychological level. Independent replications are needed to confirm that being homozygotic for valine at PRNP M129V position is associated with better psychopathological and neuropsychological scores in psychotic disorders.
Información del artículo Ambiente familiar y emoción expresada en pacientes con esquizofrenia u o... more Información del artículo Ambiente familiar y emoción expresada en pacientes con esquizofrenia u otras psicosis y en sus familiares de primer grado.
La satisfacción de los profesionales de la medicina es una preocupación en el sector sanitario y ... more La satisfacción de los profesionales de la medicina es una preocupación en el sector sanitario y su medida requiere un cuestionario multidimensional en español que estudie sus necesidades de alto nivel. Los objetivos de este estudio son adaptar el cuestionario 4Cor-nerSAT para la medida de la satisfacción profesional del personal médico y evaluar su validez en nuestro contexto. Método: Se adaptó el cuestionario al español, validándolo en profesionales médicos de hospitales de Andalucía, España. Se realizó un análisis factorial confirmatorio (AFC) para corroborar el modelo a priori y se evaluó la consistencia interna y la validez de constructo mediante el alfa de Cronbach y la correlación entre la escala y el ítem global, respectivamente. Resultados: El cuestionario adaptado se administró a 121 especialistas. El AFC corroboró las cuatro dimensiones del cuestionario (χ2=114,64, df=94, p<0,07; χ2/df=1,22; RMSEA=0,04). La consistencia interna obtuvo un α=0,92 y la correlación entre la suma de la escala y el ítem global verificó la validez de constructo(r=0,77; p<0,001). Conclusiones: Se adaptó al español el cuestionario 4CornerSAT, evidenciado una adecuada validez de constructo y consistencia interna.
Aims: From a dimensional point of view, the schizotypal features would be continuously distribute... more Aims: From a dimensional point of view, the schizotypal features would be continuously distributed in normal population and individuals with schizophrenia spectrum disorders. in the latter, differences have been found in personality traits between the diagnostic categories of the dimension, and also different schizotypy scores between them. in this study our main objective was to specify the domains and traits of pathological personality that can be considered risk factors for schizotypy. Method: SPQ and DAPP-BQ were administered to a sample of 91 subjects that were divided in four groups: psychotic patients with schizophrenia spectrum disorders, siblings of patients from this spectrum, patients with personality disorders, and healthy controls. Results: Patients with personality disorders presented the highest scores of schizotypy measured with SPQ, followed by psychotic patients, siblings, and finally the healthy controls. both groups of patients obtained higher pathological personality scores compared to siblings and controls. in the psychotic patients and their siblings emotional dysregulation, dissocial behavior and inhibition domains correlated with the SPQ factors, while in the personality disorder patients SPQ correlated only with inhibition. the trait social avoidance appears to be a predictive variable of psychometric schizotypy. Conclusions: Pathological personality underlying the schizotypy of psychotic patients of schizophrenia spectrum and their siblings is different from that of the personality disorder group. Social avoidance is a risk factor for schizotypy measured with SPQ.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2005
It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydr... more It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are risk factors for schizophrenia. We conducted a case-control study to investigate whether tHcy levels and MTHFR C677T and A1298C variants are associated with schizophrenia, giving special consideration to confounding factors. Logistic regression analysis showed that neither tHcy nor MTHFR polymorphisms were associated with schizophrenia. Homozygosity for MTHFR C677T was associated with higher tHcy concentrations in control and schizophrenia groups ( P < 0.01), which was mainly driven by the male group. The A1298C variant did not show any association with tHcy concentrations. In conclusion, these results do not confirm an independent relationship of tHcy and MTHFR genotype with risk of schizophrenia. D
Introduction: Impaired sustained and selective attention have been seen as vulnerability factors ... more Introduction: Impaired sustained and selective attention have been seen as vulnerability factors to psychotic disorders. Relatives of psychotic patients are a risk population for psychosis, and previous studies have shown that they displayed more attentional deficits compared with healthy controls. Additionally, relatives have more pathological personality and schizotypy, the least considered also to be the expression of the genetic vulnerability to schizophrenia. There are few studies that relate attention to personality factors in relatives of psychotic patients. Aims: To compare attentional performance of siblings of psychotic patients with those of healthy controls, taking into account their pathological and schizotypal personality. Methods: The Spanish version of the SPQ and the DAPP-BQ were administered to a sample of 51 subjects that were divided into four groups by a hierarchical cluster analysis: siblings with high pathological personality (SHPP), siblings with low pathological personality (SLPP), controls with high pathological personality (CHPP), and controls with low pathological personality (CLPP). In all the subjects we assessed a sustained attention index (SUA) and a selective attention index (SEA). We compared the performance of the four groups on these attentional indexes. Results: We found that SHPP had worse performance on sustained attention compared with CLPP. Specifically this difference was in the reaction time item of the SUA. Conclusions: The high schizotypy and pathological personality had an influence on sustained attentional performance in the siblings of patients with psychosis, but not in the healthy controls.
Objectives: There are few quality-of-life instruments specifically for schizophrenia; thus, the o... more Objectives: There are few quality-of-life instruments specifically for schizophrenia; thus, the objective of our study is to adapt and validate the Satisfaction with Life Domains Scale (SLDS) by Baker and Intagliata. Method: This is a validation study in which the subjects were evaluated on 2 occasions (24-48 hours). The sample is composed of people with schizophrenia from 18 to 65 years old and who were seen in one of the following centers: Sant Joan de Déu-SSM, Hospital Clínic, Hospital de Mataró and Hospital Pere Mata. The SLDS was administered, along with Positive and Negative Syndrome Scale, the Clinical General Impression for Schizophrenia, Global Assessment of Function, Disability Assessment Scale-short version, Beck Cognitive Insight, and the Strauss and Carpenter Prognostic Scale. The Cronbach α test was carried out, and the intraclass correlation coefficient was used to assess test-retest reliability, along with Pearson correlations for discriminating validity. Results: The intraclass correlation coefficients oscillated between 0.51 and 0.83. The SLDS did correlate with any of the other instruments with the exception of the Positive and Negative Syndrome Scale general subscale and the Strauss and Carpenter prognostic scale. Conclusions: The Spanish version of the SLDS was shown to be valid and reliable and provides a fast and specific measure for schizophrenia.
IntroductionThe aim of this study was to validate the Spanish version of the Strauss and Carpente... more IntroductionThe aim of this study was to validate the Spanish version of the Strauss and Carpenter Prognostic Scale for Schizophrenia (Strauss and Carpenter, 1977).
Evidence suggests that myelin alterations could predispose to schizophrenia. Reduced expression o... more Evidence suggests that myelin alterations could predispose to schizophrenia. Reduced expression of several myelin genes has been observed in schizophrenia patients. Recently, we identified the discoidin domain receptor 1 (DDR1; located at human chromosome 6p21.3) as a myelin gene in the mouse model and in a human oligodendroglial cell line. In the present study we screened for single nucleotide polymorphisms (SNPs) in the DNA from 100 schizophrenia patients. We identified a novel mutation within exon 10 that produces the amino-acid substitution N502S in the a-d isoforms, and M475V in the e isoform. However the frequency of the mutation (2%) was similar in schizophrenia patients and in control subjects. In a casecontrol assessment with 389 schizophrenic patients and 615 controls, we identified one SNP (SNP9, rs1049623) associated with schizophrenia (odds ratio = 1.44, 95% confidence interval: 1.15-1.79, adjusted P = 0.0016). This association was confirmed in haplotype analysis; the SNPs 9-10-11 (rs1049623, rs2267641 and rs2239518) haplotype remaining significant even after adjustment for multiple testing (adjusted P = 0.0136). Of note was a strong gender dependence in the association, that is, statistical significance restricted to men (adjusted P-value = 0.0002). Regression analysis of DDR1 mRNA expression in peripheral blood lymphocytes from schizophrenia patients showed that the presence of the G allele significantly decreased the relative number of mRNA copies in a dose-dependent manner (P = 0.003). These data suggest that the risk haplotype tags a cis-acting variant involved in the transcription regulation system of the gene. In conclusion, we propose the DDR1 as a new susceptibility gene for schizophrenia.
The ⑀4 allele of APOE is generally accepted to be a risk factor in Alzheimer's disease and it has... more The ⑀4 allele of APOE is generally accepted to be a risk factor in Alzheimer's disease and it has been related to other neuropsychiatric disorders, including schizophrenia. The results of several case-control studies have been inconclusive. To shed more light on this issue we carried out an association study that compared the APOE common variant in a group of 365 schizophrenia patients and 584 controls. We found no differences in the genotype distributions and allele frequencies of patients and controls. In the group of patients, we also analysed the possible influence of the ⑀4 allele in the clinical variables. The most important findings are that the age at onset (AAO) of ⑀4+ schizophrenic women, those that have one or two ⑀4 alleles, is 4 years earlier than that of ⑀4− women and their risk of suffering a negative syndrome subtype is four times greater. This was not found in schizophrenic men. Our results show that the APOE variant is not a risk factor for developing schizophrenia but that it may modulate its phenotypic expression in a sex-dependent manner. Molecular Psychiatry (2001) 6, 307-310.
Schizotypy has been proposed to be the expression of the genetic vulnerability to schizophrenia. ... more Schizotypy has been proposed to be the expression of the genetic vulnerability to schizophrenia. Schizotypal features have been associated with personality dimensions found in patients with psychosis. In this study, we compared the Dimensional Assessment of Personality Pathology - Basic Questionnaire (DAPP-BQ) scores of patients with psychosis, siblings scoring higher on schizotypy (SSHS), and siblings scoring lower (SSLS). The SSHSs displayed a DAPP-BQ profile characterized by high scores in the dimensions of affective lability, anxiousness, submissiveness, social avoidance, identity problems, oppositionality, narcissism, and restricted expression, distinguishing them from the SSLS. Due to these dimensions, SSHSs are more similar to the patients&amp;amp;amp;amp;amp;amp;amp;amp;#39; DAPP-BQ profile. The results suggest that this pathological personality profile might contribute to increase the risk of developing psychosis in siblings who have more schizotypal features.
Background: Genome-wide association studies using several hundred thousand anonymous markers pres... more Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs).
Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associa... more Disturbances in methyl-carbon metabolism, which result in hyperhomocysteinemia, have been associated with schizophrenia. Homozygosity for the T677 allele of the methylenetetrahydrofolate reductase (MTHFR) gene, which encodes for a thermolabile enzyme associated with hyperhomocysteinemia, has been found to be increased in schizophrenic patients. We have investigated whether plasma homocysteine concentration and the frequency of C677T MTHFR variant were increased in schizophrenic inpatients of a psychiatric hospital (n=210) compared with controls (n=218). There were no significant differences in plasma homocysteine concentrations between the schizophrenia and the control group. The distributions of T allele and TT genotype frequencies were similar in both groups (40% and 15%). These results show that impaired homocysteine metabolism is unlikely in schizophrenia.
Wolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode... more Wolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode and characterized by the presence of diabetes mellitus and optic atrophy. Patients and heterozygote carriers are at an increased risk of suffering psychiatric disorders. Mutations in the Wolfram gene (WFS1 ) (4p16.1) are responsible for the development of the disease, and mRNA and protein expression of WFS1 have recently been found in areas of the rat brain that can be related to the psychiatric symptoms. To test the hypothesis that WFS1 mutations in heterozygote carriers or other variants of WFS1 can predispose to mental illness. Stage 1: Exons 2, 4 and 8 of that harbour mutations in Spanish Wolfram syndrome families were examined by Single Strand Conformation Polymorphism and sequencing analysis in 43 patients with affective disorder to identify variants and mutations. Stage 2: two variants identified in stage 1 were analysed in 152 psychiatric patients (118 schizophrenia and 34 affective disorder) and 177 control subjects. Six variants (I333V Ile--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;Val, F341, N500, R708, K774, K811) and a WFS1 mutation (R818C, Arg--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;Cys) were found in the 43 patients analysed in stage 1 of the study. In stage 2, the R818C mutation was not found in the group of psychiatric patients but it was present in one control subject. The association study conducted with the I333V variant did not find significant differences in allele or genotype frequencies between patients and control subjects. Our results suggest that WFS1 is not a major susceptibility gene for the development of psychiatric disorders in our population.
Polyphenols and obesity related pathologies View project Accelerated geroncogenesis: a new experi... more Polyphenols and obesity related pathologies View project Accelerated geroncogenesis: a new experimental framework for modeling and verifying aging-driven alterations in cancer-promoting metabolites View project
The methionine/valine polymorphism at position 129 in the prion protein gene, PRNP M129V, is a kn... more The methionine/valine polymorphism at position 129 in the prion protein gene, PRNP M129V, is a known risk factor for Creutzfeldt-Jakob disease (CJD). Psychiatric manifestations including psychosis are common in the early phase of CJD and it has therefore been hypothesized that the prion protein could be involved in psychotic disorders. Moreover, among the various hypothesized functions of the prion protein, a role in synaptic activity has been described. We have studied the PRNP M129V variant with regard to psychotic disorders from two perspectives: first as a genetic risk factor and second as a genetic factor influencing phenotypic variation. A case-control study of 482 psychotic patients and 502 controls indicated that differences between patients and controls were not present in genotype distributions or allele frequencies. We also studied the influence of this variant in psychopathological symptomatology and neuropsychological performance in a subgroup of 159 psychotic patients. In our sample, patients homozygous for valine at this position presented less severe scores in the general psychopathological subscale (p=0.003) and in the sum of the total items (p=0.007) of the Positive and Negative Syndrome Scale (PANSS). Also, homozygote VV patients presented better scores in most neuropsychological tests, the most significant result of which was for delayed visual memory (p=0.021). In summary, our results do not support the hypothesis that M129V is a susceptibility factor for psychotic disorders. However, it could influence their phenotypic variation at the psychopathological and neuropsychological level. Independent replications are needed to confirm that being homozygotic for valine at PRNP M129V position is associated with better psychopathological and neuropsychological scores in psychotic disorders.
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