Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia.

Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders. Schizophrenia is a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654 schizophrenic patients and 604 controls for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39 Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability to schizophrenia (odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated with schizophrenia, as well as for common CNVs that may act as susceptibility factors by disturbing glutathione metabolism.

Minor physical anomalies and schizophrenia: literature review.

Many authors view schizophrenia as a neurodevelopmental disorder. Knowledge of whether patients have morphologic variants that occur during the development of different anatomic areas of the brain and an understanding of the relation between such variants and brain development or prenatal exposure to possible noxae could provide clues about the events that lead to schizophrenia. Nonspecific morphologic variants that occur during the first and second trimesters of gestation, which are known as minor physical anomalies (MPA) and can be used as disease risk markers insusceptible persons, have been related with schizophrenia,independently of the anatomic region where they occur. The importance of these anomalies in relation to schizophrenia is that they may reflect a substrate (schizotaxia) that is either inherited or acquired as a consequence of injury(ies)that would result in the disease in susceptible persons. This idea is also supported by indirect evidence provided by family studies, among others. On the other hand, the role of MPA in other neurodevelopmental orders is similar to the role proposed in schizophrenia.

Psychopathology and personality traits in psychotic patients and their first-degree relatives.

Personality dimensions have been associated with symptoms dimensions in schizophrenic patients (SP). In this paper we study the relationships between symptoms of functional psychoses and personality dimensions in SP and their first-degree relatives (SR), in other psychotic patients (PP) and their first-degree relatives (PR), and in healthy controls in order to evaluate the possible clinical dimensionality of these disorders. Twenty-nine SP, 29 SR, 18 PP, 18 PR and 188 controls were assessed using the temperament and character inventory (TCI-R). Current symptoms were evaluated with positive and negative syndrome scale (PANSS) using the five-factor model described previously (positive [PF], negative [NF], disorganized [DF], excitement [EF] and anxiety/depression [ADF]). Our TCI-R results showed that patients had different personality dimensions from the control group, but in relatives, these scores were not different from controls. With regard to symptomatology, we highlight the relations observed between harm avoidance (HA) and PANSS NF, and between self-transcendence (ST) and PANSS PF. From a personality traits-genetic factors point of view, schizophrenia and other psychosis may be initially differentiated by temperamental traits such as HA. The so-called characterial traits like ST would be associated with the appearance of psychotic symptoms.

Mood changes after delivery: role of the serotonin transporter gene.

BACKGROUND: Polymorphic variations in the serotonin transporter gene (5-HTT) moderate the depressogenic effects of tryptophan depletion. After childbirth there is a sharp reduction in brain tryptophan availability, thus polymorphic variations in 5-HTT may play a similar role in the post-partum period. AIMS: To study the role of 5-HTT polymorphic variations in mood changes after delivery. METHOD: One thousand, eight hundred and four depression-free Spanish women were studied post-partum. We evaluated depressive symptoms at 2-3 days, 8 weeks and 32 weeks post-partum. We used diagnostic interview to confirm major depression for all probable cases. Based on two polymorphisms of 5-HTT (5-HTTLPR and STin2 VNTR), three genotype combinations were created to reflect different levels of 5-HTT expression. RESULTS: One hundred and seventy-three women (12.7%) experienced major depression during the 32-week post-partum period. Depressive symptoms were associated with the high-expression 5-HTT genotypes in a dose-response fashion at 8 weeks post-partum, but not at 32 weeks. CONCLUSIONS: High-expression 5-HTT genotypes may render women more vulnerable to depressive symptoms after childbirth.

Sustained and selective attention deficits as vulnerability markers to psychosis.

The first descriptions of schizophrenia emphasized attention problems patients with schizophrenia have but recent results evidence that other psychotic disorders share them. We compared the performance in sustained and selective attention between psychotic patients (P), their healthy first degree relatives (R) and healthy volunteers (C) to prove whether these alterations could be an endophenotype of vulnerability to psychosis. We also compared the performance of schizophrenic patients (SZP) and that of patients with other functional psychoses (OP) in order to prove whether these alterations are specific of any psychotic disorder. Seventy-six P, 70 R and 39 C were included in the study. A selective attention index, comprising TMT A and B and Stroop Test, and a sustained attention index comprising the Continuous Performance Test were calculated. We conducted an univariant general linear model to compare three group performances in these indexes, with age, sex and years of education as a covariables. We found significant differences between the indexes when we compared P, R and C. No differences in performance were found between SZP and OP. Our data showed that sustained and selective attention alterations could be a vulnerability factor to psychotic disorders in general, but they were not specific of schizophrenia.

Schizotypal traits and cognitive performance in siblings of patients with psychosis.

INTRODUCTION: Schizotypy has been proposed to be the expression of genetic vulnerability to schizophrenia. The available literature shows cognitive similarities between schizotypy and schizophrenia, with mildly impaired performance being associated with schizotypy. This study aims to determine the relationship between schizotypy and cognitive performance in siblings of patients with psychosis. METHODS: Schizotypal features and cognitive performance on a neuropsychological battery were compared between 48 siblings of patients with psychosis and 44 healthy controls. The relationships between schizotypy and cognitive performance were analysed by controlling the condition of being a sibling. RESULTS: Siblings showed poorer performance on vigilance/sustained attention (M = 37.6; SD = 7.1) and selective attention/interference control/working memory (M = 23.28; SD = 2.7) tasks. The variance in vigilance/sustained attention performance was explained, at 30%, by the interpersonal factor of schizotypy on the suspiciousness dimension and the condition of being a sibling. CONCLUSIONS: Interpersonal features of schizotypy in siblings of patients with psychosis are associated with deficits in vigilance/sustained attention performance.

Anticipation is not associated with CAG repeat expansion in parent-offspring pairs of patients affected with schizophrenia.

With the rationale that a disease that presents with anticipation could be associated with expansion of trinucleotide repeats, we selected parent-offspring pairs of schizophrenia patients with earlier age at onset in the filial generation to measure the expansion of CAG repeats using the repeat expansion detection (RED) method. Intergenerational comparisons were made for age at onset, length of CAG repeats, and clinical variables. Although the patients from the filial generation became affected 13 years earlier than the parents (P < 0.0005), we did not find larger CAG repeats in the offspring. No association was found between size of CAG repeat and age at onset or with any other clinical variable. Overall, the frequency of patients with CAG repeats longer than 40 was 32%, which was similar to that observed in control subjects (27%). It is particularly noteworthy that in 86% of the pairs, the mother was the affected parent. In this Spanish sample with parent-offspring pairs presenting schizophrenia with clinical anticipation and apparent female bias of transmission, neither the phenomenon of anticipation nor disease status was associated with the expansion of CAG repeats.

Association study of schizophrenia with polymorphisms at six candidate genes.

Clinical studies have shown that there is a genetic contribution to the pathogenesis of schizophrenia. The molecular mechanisms of effective antipsychotic drugs and recent advances in neural development suggest that several dopamine receptor, serotonin receptor and neurotrophic factor genes might be involved in the disorder. In this study, we assessed the associations between schizophrenia and polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3), the serotonin 2A receptor (5HTR2A), the brain-derived neurotrophic factor (BDNF), the ciliary neurotrophic factor (CNTF) and the neurotrophin-3 (NT-3) genes. Our results suggest that the polymorphisms at the DRD3, 5HTR2A, CNTF and BDNF gene loci are unlikely to make our sample more genetically susceptible to schizophrenia. However, we found significant differences in microsatellite allele frequencies between schizophrenic and control groups for DRD2 in the whole sample and for DRD2 and NT-3 only in women. Therefore, clinical differences in the presentation of schizophrenia between gender might be related to genetic factors.

Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia.

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.

[A genetic-behavioral alternative to the personality disorders: the Livesley dimensional model]. / Una alternativa genético-conductual a los trastornos de la personalidad: el modelo dimensional de Livesley.

In the personality disorder section of the DSM-V research agenda, the authors stress the need for studies on the relevance of a change from diagnostic categorical models to dimensional ones. These studies should identify the underlying genetic and neurobiologic mechanisms and appropriate representation on the dimensions of clinical criteria as cognitive disturbances, identity conflicts and attachment. Livesley's behavioral-genetic model represents an interesting dimensional paradigm of personality pathology. It was elaborated deductively from the consensus and statistical refinement of data collected by a large number of clinicians from different psychopathological tendencies. The traits are made operative in the "Dimensional Assessment of Personality Pathology-Basic Questionnaire" (DAPP-BQ) tool with 18 dimensions (that became 30) and 4 higher rank factors (adapted to Spanish by Gutiérrez- Zotes et al, 2008). The model has shown an appropriate relationship with important personality paradigms and good predictive power for personality disorders. The authors incorporate methods of variance breakdown for statistical processing of the genetic-environmental mechanism underlying each personality disorder dimension. Homologation of DSM-IV-TR criteria for personality disorders is proposed so that the model's dimensions capture and represent the clinical complexity of the symptoms in a convenient manner for the new location in DSM-V.

[Family environment and expressed emotion in patients with schizophrenia or other psychoses and in their first-degree relatives]. / Ambiente familiar y emoción expresada en pacientes con esquizofrenia u otras psicosis y en sus familiares de primer grado.

INTRODUCTION: Family has always been considered a key milestone for the development of the human psyche. Furthermore, in relationship with mental disorders we know that certain aspects of family environment change the course of some of these disorders. This study has aimed to compare the family setting perception of schizophrenic patients vs. other psychotic patients, their first-degree relatives and to see if the expression of the disorder is related with that perception. METHOD: The study included 112 subjects: 41 patients, 41 first-degree relatives and 30 normal controls. Patients were included in the group of as schizophrenic (n=24) or non-schizophrenic psychosis (n=17) following DSM-IV criteria diagnosis using the SCAN interview and were evaluated with the Family Environment Scale (FES) and PANSS. Descriptive analysis, group comparisons and correlation studies were used as statistical methods. RESULTS: No statistically significant differences were found when comparing FES between both group of patients, nor between patients and relatives, although psychotic patients presented a tendency to score higher on almost all the FES scales and dimensions. We found significantly positive correlations between patients and their own relatives in the FES scales. CONCLUSIONS: Although not with statistical significance, non-schizophrenic psychotic patients and their relatives have a slightly different family environment perception than their schizophrenic counterparts: more conflictivity; more rule strictness and more planning needs. High levels of expressed emotion were related with a predominance of positive symptoms in psychotic patients.

The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia.

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 case-control 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.

Psychometric properties of the abbreviated Spanish version of TCI-R (TCI-140) and its relationship with the Psychopathological Personality Scales (MMPI-2 PSY-5) in patients.

INTRODUCTION: The short version of the Temperament and Character Inventory-Revised (TCI-R), the TCI-140, is presented. This study aimed: a) to obtain the psychometric properties of TCI-140; b) to analyze the relationship with the normal version of the TCI-R, and c) to study its convergent validity with the MMPI-2 PSY-5. METHOD: The TCI-R and MMPI-2 PSY-5 scales were administered to a sample of consecutive psychiatric inpatients with differential Axis I and II diagnoses. RESULTS: It was found that the TCI-140 dimensions showed reliability coefficients ranging from 0.67 (Reward dependence [RD]) to 0.86 (Self-Transcendence [ST]) and the reliability coefficients of PSY-5 ranging from 0.68 (CON) to 0.86 (NE/NEU). Correlations for the dimensions with the TCI-R original 240-item version and TCI-R 140 item version ranged from 0.91 (Self-Directedness [SD]) to 0.97 (ST). The dimensions had a normal distribution. Correlations of TCI-140 scales with PSY-5 scales provided preliminary evidence supporting the convergent validity of the constructs. Then, Novelty Seeking (NS) was associated with low Constraint, Harm Avoidance (HA) was associated with low Aggressiveness and Positive Emotionality/ Extraversion, and also with high Negative Emotionality/Neuroticism, Reward Dependence (RD) was associated with high Positive Emotionality/Extraversion. Persistence (PS) was related to high aggressiveness, and Positive Emotionality/ Extraversion. On the other hand, SD was correlated with low Psychoticism, and Negative Emotionality/Neuroticism, and also with high Positive Emotionality/Extraversion. Cooperativeness (C) had a relationship to high constraint and low psychoticism. Finally ST was associated with high psychoticism and Positive Emotionality/Extraversion. CONCLUSIONS: The short Spanish version of TCI-R is a useful inventory for the evaluation of the principals dimensions of temperament and character.

[Retrospective study of prodromal symptoms in schizophrenia]. / Estudio retrospectivo de los síntomas prodrómicos en la esquizofrenia.

INTRODUCTION: There are some non-psychotic symptoms that can forecast the onset of psychosis. Discovering the differences between the symptoms that lead to disease and those that do not makes it possible to identify them and permits early treatment of the disease. METHODS: A sample of 689 schizophrenic patients was analyzed retrospectively. This sample was obtained from the clinical records database of the University Psychiatric Hospital Institut Pere Mata. Data were analyzed with the SPSS version 9.0 statistical package. RESULTS: The most frequent prodromal symptoms of the sample were the delusional ones, the disorganized ones and the neurotic ones. The prodromal symptoms were equally distributed in both genders. In the subtypes, paranoids showed more delusional symptoms, whereas the nonparanoids presented more disorganized symptoms. Acute onsets had more delusional prodromal symptoms whereas the insidious onsets showed more disorganized ones. CONCLUSIONS: In the prodromal stages of shizophrenia, we can also find the community neurotic prevalences regarding gender. The higher rate of neurotic symptoms in the nonparanoid subtype would be explained by the inclusion of the schizoaffective category, whereas the higher rate of disorganized symptoms categories would be due to the hebephrenic and simple categories. The latter would also explain the prodromal differences in the onset type.

Anticipation and imprinting in Spanish families with schizophrenia.

Evidence of imprinting and anticipation, two genetic phenomena that are correlated with clinical sequelae, was assessed in familial schizophrenia. A sample of patients (n=291) who fulfilled the ICD-9 criteria for schizophrenia and corresponding to the familial-type and sporadic-type of the disorder was recruited. Clinical anticipation and imprinting variables such as age at onset (AAO), schizophrenia subtype, course of disease and onset type were assessed over parental (G1) and filial (G2) generations in both schizophrenia types. Anticipation assessment indicated significant differences in mean AAO between parent-offspring pairs in unilineal families. These differences were not explained by a cohort effect. Imprinting assessment indicated non-significant differences in AAO between the offspring of affected mothers and the offspring of affected fathers. The results obtained for other clinical variables were non-conclusive. The results suggest that anticipation, but not imprinting, is operative in schizophrenia.

[Temperament and Character Inventory Revised (TCI-R). Standardization and normative data in a general population sample]. / Inventario del Temperamento y el Carácter-Revisado (TCI-R). Baremación y datos normativos en una muestra de población general.

INTRODUCTION: The revised version of the Temperament and Character Inventory (TCI-R), a tool designed by C. R. Cloninger for the evaluation of the seven dimensions defined in his psychobiological model of personality, was translated and adapted to Spanish. The aim of the study was to obtain normative data and scales with T-scores in a incidental sample of the general Spanish population. METHODS: After adaptation to Spanish, the tool was administered to 400 subjects from several areas of Spain. The sample is stratified according to age and gender according to the year 2001 Spanish population census. We have studied the differences between men and women and the association between age and dimensions. We have checked the normal distribution of the traits, and proceeded with the standardization and normalization of the scores. RESULTS: We present the mean and standard deviation according to sex for each of the main dimensions and subscales. The scores of the main dimensions obtained for general population according to gender show a normal distribution that has allowed us to standardize them into T-scores. The reliability of the dimensions is high. There are differences in the means depending on gender: women scored higher in Harm Avoidance, Reward Dependence and Cooperativeness. Men scored higher in Persistence. There were no high correlations between age and the dimensions. CONCLUSIONS: The Spanish version of the new TCI-R is an adequate tool for the study of personality dimensions of normal population.

Schizophrenic women with the APOE epsilon 4 allele have a worse prognosis than those without it.

The epsilon 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 epsilon 4 allele in the clinical variables. The most important findings are that the age at onset (AAO) of epsilon 4+ schizophrenic women, those that have one or two epsilon 4 alleles, is 4 years earlier than that of epsilon 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.

Analysis of amino-acid and nucleotide variants in the spinocerebellar ataxia type 1 (SCA1) gene in schizophrenic patients.

Several loci-containing genes that might harbour mutations predisposing to schizophrenia have recently been identified. The locus on chromosome 6p has been detected by several groups and appears to predispose to schizophrenia in 15%-30% of the pedigrees in one of these studies. The chromosome 6p locus for schizophrenia spans about 30 cM, between markers D6S296 and D6S276. The current transcription map of the 6p22-24 region includes three expressed sequence tags and six genes, one of which is the spinocerebellar ataxia type 1 (SCA1) gene. Patients with SCA1 have the CAG repeat sequence, which encodes a polyglutamine stretch in the ataxin-1 protein, expanded beyond the normal range. More recently, linkage disequilibrium between schizophrenia and the SCA1 CAG repeat has been reported. SCA1 is a good candidate gene for the schizophrenia-susceptibility locus on chromosome 6p as indicated by its expression pattern. We have studied the coding region of the SCA1 gene (exons 8 and 9) in samples from schizophrenia patients and have identified two amino-acid variants (S186C and P754S) and three nucleotide polymorphisms (1409A/G, 1865T/C and 2150A/G). One of the amino-acid changes (S186C) was present in two schizophrenic brothers from one family and in a schizophrenic patient and a non-affected subject of a second family but it was not detected in 100 unrelated subjects from the general population. S186C and other variants may be of relevance to the complex genetic factors involved in schizophrenia phenotypes.

Anomalías físicas menores y esquizofrenia: revisión de la literatura / Minor physical anomalies and schizophrenia: literature review

La esquizofrenia es considerada una enfermedad del neurodesarrollo por muchos autores. Saber si en los pacientes hay variantes morfológicas producidas durante el desarrollo de áreas anatómicas diferentes al cerebro y entenderla relación de esas variantes con el desarrollo cerebral o con la exposición prenatal a posibles noxas, podría dar pistas sobre los eventos que llevan al trastorno. Variantes morfológicas inespecíficas producidas durante el primer y segundo trimestre de gestación denominadas anomalías físicas menores (AFM) que pueden ser usadas como marcadores de riesgo de una enfermedad en personas susceptibles se vienen relacionando con la esquizofrenia, independientemente de la región anatómica en la que se presenten. La importancia de estas anomalías en relación con la esquizofrenia estaría dada porque podrían ser el reflejo de un sustrato (esquizotaxia) heredado o adquirido como consecuencia de alguna injuria(s) que resultaría en la enfermedad en personas susceptibles. Esta idea se apoya además en evidencia indirecta proporcionada por estudios con familias, entre otros. Por otro lado, el rol de las AFM en otros trastornos del neurodesarrollo es similar al propuesto en la esquizofrenia (AU)

Schizophrenia is considered for many authors as a disease of neurodevelopment. Know if there are morphological variants in the patients produced during development of anatomical areas others than the brain and understand the relation of those variants with the brain development or with prenatal exposition to possible noxas could give clues about the events conducting to the disorder. Morphological unspecific variants generated during the first and second gestation trimester denominated minor physical anomalies (MPA) that can be used as risk markers of a disease in susceptible persons have been related with schizophrenia independently of the anatomical region they are. The importance of these anomalies in relation with schizophrenia is that they might be the reflex of a substratum (schizotaxia) inherited or acquired as a consequence of some injuries(s) that become into the disease in susceptible persons. Moreover this idea is supported in indirect evidence provided by studies with families, between others. In the other hand the role of the MPA in other disorders of neurodevelopment is similar to the one proposed in schizophrenia (AU)

Una alternativa genético-conductual a los trastornos de la personalidad: el modelo dimensional de Livesley / A genetic-behavioral alternative to the personality disorders: the Livesley dimensional model

En la agenda de investigación para el DSM-V, sección de los trastornos de la personalidad, se enfatiza la necesidad de estudios sobre la pertinencia de un cambio de modelo de categorías diagnósticas por uno dimensional. Estos trabajos deberían identificar los mecanismos genéticos y neurobiológicos subyacentes así como la adecuada representación, en las dimensiones, de criterios clínicos como las alteraciones cognitivas, los conflictos de la identidad y del vínculo. El modelo genético conductual de Livesley se constituye como un interesante paradigma dimensional de la patología de la personalidad. Ha sido elaborado de forma inductiva a partir del consenso y depuración estadística de un gran número de clínicos de diferentes corrientes psicopatológicas. Los rasgos se operativizan en el instrumento «Valoración Dimensional de la Personalidad Patológica-Cuestionario Básico» (DAPPBQ) con 18 dimensiones (posteriormente 30) y cuatro factores de rango superior (adaptado al español por Gutiérrez-Zotes et al., 2008). El modelo ha demostrado una adecuada relación con importantes paradigmas de personalidad y buena capacidad predictiva con los trastornos de la personalidad. Los autores incorporan métodos de descomposición de la varianza para depurar el mecanismo genético y ambiental que subyace a cada dimensión de la patología de la personalidad. Se propone una homologación de los criterios DSM-IV-TR para los trastornos de la personalidad, en donde las dimensiones del modelo capturan y representan la complejidad clínica de los síntomas de forma conveniente en la nueva ubicación para el DSM-V (AU)

In the personality disorder section of the DSM-V research agenda, the authors stress the need for studies on the relevance of a change from diagnostic categorical models to dimensional ones. These studies should identify the underlying genetic and neurobiologic mechanisms and appropriate representation on the dimensions of clinical criteria as cognitive disturbances, identity conflicts and attachment. Livesley’s behavioral-genetic model represents an interesting dimensional paradigm of personality pathology. It was elaborated deductively from the consensus and statistical refinement of data collected by a large number of clinicians from different psychopathological tendencies. The traits are made operative in the «Dimensional Assessment of Personality Pathology-Basic Questionnaire»(DAPP-BQ) tool with 18 dimensions (that became 30) and4 higher rank factors (adapted to Spanish by Gutiérrez-Zotes et al, 2008). The model has shown an appropriate relationship with important personality paradigms and good predictive power for personality disorders. The authors incorporate methods of variance breakdown for statistical processing of the genetic-environmental mechanism underlying each personality disorder dimension. Homologation of DSM-IV-TR criteria for personality disorders is proposed so that the model's dimensions capture and represent the clinical complexity of the symptoms in a convenient manner for the new location in DSM-V (AU)