Initial validation of the Spanish childhood trauma questionnaire-short form: factor structure, reliability and association with parenting.

The present study examines the internal consistency and factor structure of the Spanish version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the association between the CTQ-SF subscales and parenting style. Cronbach's α and confirmatory factor analyses (CFA) were performed in a female clinical sample (n = 185). Kendall's ι correlations were calculated between the maltreatment and parenting scales in a subsample of 109 patients. The Spanish CTQ-SF showed adequate psychometric properties and a good fit of the 5-factor structure. The neglect and abuse scales were negatively associated with parental care and positively associated with overprotection scales. The results of this study provide initial support for the reliability and validity of the Spanish CTQ-SF.

Relationships between childhood maltreatment, parenting style, and borderline personality disorder criteria.

This study examines the relationship of different types of childhood maltreatment and the perceived parenting style with borderline personality disorder (BPD) criteria. Kendall's Tau partial correlations were performed controlling for the effect of simultaneous adverse experiences and Axis I and II symptoms in a sample of 109 female patients (32 BPD, 43 other personality disorder, and 34 non-personality disorder). BPD criteria were associated with higher scores on emotional and sexual abuse, whereas parenting style did not show a specific association with BPD. Findings of the present study help clarify the effects of overlapping environmental factors that are associated with BPD.

Spanish adaptation of the Beck Cognitive Insight Scale (BCIS) for schizophrenia.

INTRODUCTION: The Beck Cognitive Insight Scale has been designed to evaluate the cognitive insight capacity, that is to say, the practice of self-reflectiveness as a meta-cognitive mechanism for examining and analysing the disorder's symptoms, it also permits a continuous re-evaluation of inadequate interpretations. METHODOLOGY: The aim of this study is to examine the psychometric properties, the dimensional structure and the internal validity of the Spanish version of Beck's Cognitive Scale of Insight (BCIS). In this paper we also analyse its relation with the Positive and Negative Symptoms Scale (PANSS). The Cognitive Insight Scale was translated and adapted to Spanish with 129 in- and out-schizophrenic patients. RESULTS: Principal component analysis showed a two-factor structure that was similar to the original one, recognizable as self-reflectiveness (R) and self-certainty (C) with similar reliability as the American version. Self-reflectiveness and the R-C index correlated with loss of insight of the PANSS scale. In general, BCIS showed significant associations with the PANSS subscales. Out patients scored self-reflectiveness and R-C index signicantly higher than in-patients and lower in self-certainty. CONCLUSION: Psychometric properties obtained with the adapted Spanish version of BCIS guarantee the adequate evaluation of cognitive insight.

Adaptación española de la Escala de Insight Cognitivo de Beck (EICB) en esquizofrénicos / Spanish Adaptation of the Beck Cognitive Insight Scale (BCIS) for Schizophrenia

Introducción. La Escala de Insight Cognitivo de Beck ha sido diseñada para evaluar la capacidad de insight cognitivo esto es, la práctica de la auto-reflexión como mecanismo metacognitivo de examen y análisis de los síntomas de la enfermedad que permite la reevaluación continua de interpretaciones inadecuadas. Metodología. Este estudio examina las propiedades psicométricas, la estructura dimensional y la validez interna de la versión española de la Escala de Insight Cognitivo de Beck (EICB). Igualmente se analiza su relación con la Escala de Síndrome Positivo y Negativo en Esquizofrenia (PANSS). La escala de Insight Cognitivo fue traducida y adaptada al castellano en 129 pacientes esquizofrénicos ingresados y no ingresados. Resultados. El análisis de componentes principales mostró una estructura de dos factores semejantes a la original reconocibles como auto-reflexión (R) y auto-certeza (C), con similar fiabilidad a la versión americana. Auto-reflexión y el índice R-C correlacionaron con pérdida de insight de la PANSS. En general la EICB se asoció significativamente con subescalas de la PANSS. Los pacientes comunitarios puntuaron significativamente más alto en autoreflexión y el índice R-C que los ingresados y más bajo en autocerteza. Conclusión. Las propiedades psicométricas obtenidas con la versión española adaptada de la EICB garantizan la adecuada evaluación del insight cognitivo (AU)

Introduction. The Beck Cognitive Insight Scale has been designed to evaluate the cognitive insight capacity, that is to say, the practice of self-reflectiveness as a meta-cognitive mechanism for examining and analysing the disorder’s symptoms, it also permits a continuous reevaluation of inadequate interpretations. Methodology. The aim of this study is to examine the psychometric properties, the dimensional structure and the internal validity of the Spanish version of Beck’s Cognitive Scale of Insight (BCIS). In this paper we also analyse its relation with the Positive and Negative Symptoms Scale (PANSS). The Cognitive Insight Scale was translated and adapted to Spanish with 129 in- and out- schizophrenic patients. Results. Principal component analysis showed a two factor structure that was similar to the original one, recognizable as self-reflectiveness (R) and self-certainty (C) with similar reliability as the American version. Self-reflectiveness and the R-C index correlated with loss of insight of the PANSS scale. In general, BCIS showed significant associations with the PANSS subscales. Out patients scored self-reflectiveness and R-C index signicantly higher than in-patients and lower in self-certainty. Conclusion: Psychometric properties obtained with the adapted Spanish version of BCIS guarantee the adequate evaluation of cognitive insight (AU)

Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia.

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). METHODS: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures. RESULTS: The 5 independent nsSNPs with false discovery rate q ≤ .25, as well as 13 additional nsSNPs at p < .01 and located in functional candidate genes, were genotyped in the replication samples. One SNP, rs13107325, located at the metal ions transporter gene SLC39A8, reached significance in the combined sample after Bonferroni correction (trend test, p = 2.7 × 10(-6), allelic odds ratio = 1.32). This SNP presents minor allele frequency of 5% to 10% in many European populations but is rare outside Europe. We also confirmed the polygenic component of susceptibility. CONCLUSIONS: Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis.

Increased morning adrenocorticotrophin hormone (ACTH) levels in women with postpartum thoughts of harming the infant.

INTRODUCTION: Some postpartum women experience intrusive thoughts of harming the infant. The hypothalamic-pituitary-adrenal (HPA) axis, which has been linked to postpartum depression, may play a role in the aetiology of postpartum thoughts of harming the infant. We aimed to study whether HPA axis hormones measured early postpartum are related to postpartum intrusive thoughts. METHOD: 132 women who delivered a child at a university hospital participated in a follow-up study with visits at 2-3 days postpartum and 8th week postpartum. Participants were assessed for trait anxiety, social support, peripartum or postpartum anxiety or depression, stressful life events and obstetric variables including perinatal complications and lactation. Postpartum thoughts of harming the infant were assessed with a semi-structured interview. Serum cortisol, and plasma CRH and ACTH levels were measured within 48 h postpartum at 8-9 AM. A logistic regression was performed to explore the relationship between clinical variables, hormonal measures and postpartum intrusive thoughts. RESULTS: Patients with postpartum thoughts of harming the infant had, when compared to those women without intrusive thoughts, higher ACTH levels (7.59 pmol/L vs 5.09 pmol/L, p<0.05) without significant differences in CRH or cortisol levels. In the logistic regression analysis, adjusted for breast-feeding and psychopathological status, only ln ACTH was associated with the presence of postpartum thoughts of harming the infant (OR=5.2, CI 95% 1.2-22.6, p=0.029). No other clinical variables were associated with postpartum intrusive thoughts. CONCLUSIONS: Our study suggests that a dysregulation of the hypothalamic-pituitary-adrenal axis may play a role in the aetiology of postpartum thoughts of harming the infant.

Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder.

Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3' near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p=0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity.

Thyroid function 48h after delivery as a marker for subsequent postpartum depression.

Physiological changes during gestation and after delivery are associated with postpartum thyroid dysfunction, which is due to thyroid autoimmunity in some cases. Postpartum thyroid dysfunction, in turn, has been associated with postpartum depression (PPD). The aim of the present study was to evaluate whether thyroid function immediately after delivery can predict postpartum depression at 8 weeks and 32 weeks after delivery. This study examined 1053 postpartum Spanish women without a previous history of depression. We evaluated depressive symptoms at 48h, 8 weeks and 32 weeks postpartum and used a diagnostic interview to confirm major depression for all probable cases. Free thyroxin (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and C-reactive protein (CRP) were assayed at 48h postpartum. Binary and multivariate logistic regression analyses were performed to determine independent risk factors for PPD. Although 152 women (14.4%) had high TPOAb (>27IU/mL) and slightly elevated TSH concentrations with normal fT4, we did not find any association between thyroid function and PPD. This thyroid dysfunction was not associated with CRP concentrations that were outside of the normal range (>3mg/L). We conclude that thyroid function at 48h after delivery does not predict PPD susceptibility.

Comorbilidad de la depresión mayor con otros trastornos mentales comunes en pacientes de atención primaria / Comorbidity of major depression with other common mental disorders in primary care patients

Introducción: La comorbilidad psiquiátrica influye en el impacto, el pronóstico y el manejo de la depresión.Objetivos: Determinar la prevalencia de otros trastornos mentales comunes en pacientes con depresión mayor y analizar sus relaciones de comorbilidad.Diseño: Estudio transversal en doble fase: a) cribado (test de Zung), y b) entrevista psiquiátrica estandarizada.Emplazamiento: 10 centros de salud de la provincia de Tarragona.Pacientes: Se cribó a 906 pacientes consecutivos. En la segunda fase fueron evaluados los 209 pacientes con resultado positivo y 97 con resultado negativo (1/7 aleatorio).Análisis: En el análisis estadístico se usaron ponderaciones atendiendo al muestreo en doble fase. Se determinó la frecuencia con que la distimia, el trastorno de ansiedad generalizada, el trastorno de pánico y el trastorno desomatización se presentabanconcomitantemente con la depresión mayor. Se compararon las características de los pacientes deprimidos según diversos grados de comorbilidad.Resultados: En el 45,7%(intervalo de confianza [IC] del 95%, 32,8–59,2) de los pacientes con depresión mayor coexistía un trastorno mental más, dos en el 19,9% (IC del 95%, 13,7–27,9) y tres trastornos mentales más en el 8,3%(IC del 95%, 4,5–14,8). El trastorno deansiedad generalizada estaba presente en el 55,2% de los deprimidos(IC del 95%, 41,6–68), el trastorno de pánico en el 33,8% (IC del 95%, 21,1–47,1), la distimia en el 15,7% (IC del 95%, 10,3–23,4) y el trastorno de somatización en el 6,6% (IC del 95%, 3,3–12,8). En los grupos de pacientes con comorbilidad la depresión fue más severa y con mayor impacto funcional. No hubo diferencias en las variables relacionadas con el manejo clínico.Conclusiones: La comorbilidad psiquiátrica de la depresión es común en atención primaria. En la mayoría de los pacientes deprimidos coexisten otros trastornos, frecuentemente de ansiedad(AU)

AimsTo determine the prevalence of other common mental disorders in patients with major depression and to analyse their associated comorbidities.SettingsTen health centres in the province of Tarragona.PatientsA total of 906 consecutive patients were screened. In the second stage, the 209 patients who gave a positive result and 97 patients who gave a negative result (1/7 at random) were evaluated.AnalysisThe statistical analysis used weights that took into account the two-stage sampling. The frequency with which dysthymia, generalised anxiety disorder, panic disorder and somatisation disorder presented concomitantly with major depression was determined. The characteristics of the depressed patients were compared for different degrees of comorbidity.ResultsIn 45.7% (95% CI, 32.8–59.2) of patients with major depression there was one other coexisting mental disorder, in 19.9% (95% CI, 13.7–27.9) two more mental disorders and in 8.3% (95% CI, 4.5–14.8) three more mental disorders. Generalised anxiety disorder was present in 55.2% of depressed patients (95% CI, 41.6–68), panic disorder in 33.8% (95% CI, 21.1–47.1), dysthymia in 15.7% (95% CI, 10.3–23.4) and somatisation disorder in 6.6% (95% CI, 3.3-12.8). In the groups of patients with comorbidity, the depression was more severe and had a greater functional impact. There were no differences in the clinical management variables.ConclusionsPsychiatric comorbidity of depression is common in primary care. Most depressed patients suffer from other disorders, often anxiety(AU)

[Comorbidity of major depression with other common mental disorders in primary care patients]. / Comorbilidad de la depresión mayor con otros trastornos mentales comunes en pacientes de atención primaria.

INTRODUCTION: Psychiatric comorbidity affects the impact, the prognosis and the management of depression. AIMS: To determine the prevalence of other common mental disorders in patients with major depression and to analyse their associated comorbidities. DESIGN: Two-stage cross-sectional study: a) screening (Zung's Self-Rating Depression Scale); b) a standardised psychiatric interview. SETTINGS: Ten health centres in the province of Tarragona. PATIENTS: A total of 906 consecutive patients were screened. In the second stage, the 209 patients who gave a positive result and 97 patients who gave a negative result (1/7 at random) were evaluated. ANALYSIS: The statistical analysis used weights that took into account the two-stage sampling. The frequency with which dysthymia, generalised anxiety disorder, panic disorder and somatisation disorder presented concomitantly with major depression was determined. The characteristics of the depressed patients were compared for different degrees of comorbidity. RESULTS: In 45.7% (95% CI, 32.8-59.2) of patients with major depression there was one other coexisting mental disorder, in 19.9% (95% CI, 13.7-27.9) two more mental disorders and in 8.3% (95% CI, 4.5-14.8) three more mental disorders. Generalised anxiety disorder was present in 55.2% of depressed patients (95% CI, 41.6-68), panic disorder in 33.8% (95% CI, 21.1-47.1), dysthymia in 15.7% (95% CI, 10.3-23.4) and somatisation disorder in 6.6% (95% CI, 3.3-12.8). In the groups of patients with comorbidity, the depression was more severe and had a greater functional impact. There were no differences in the clinical management variables. CONCLUSIONS: Psychiatric comorbidity of depression is common in primary care. Most depressed patients suffer from other disorders, often anxiety.

A common haplotype of DRD3 affected by recent positive selection is associated with protection from schizophrenia.

The number and frequency of susceptibility alleles at loci associated to most psychiatric disorders is largely unknown, in spite of its relevance for the design of studies aiming to find these alleles. Both, common polymorphisms and rare mutations may contribute to the genetic susceptibility to complex psychiatric disorders, being the relative relevance of each type of variation currently under debate. Here, we confirmed the existence of a common protective haplotype against schizophrenia at the dopamine D(3) receptor (DRD3) gene, by replication and pooled analysis with previous data (Mantel-Haenszel chi(2) P value = 0.00227; OR = 0.79, 95% CI 0.68-0.92, based on 794 cases and 1,078 controls from three independent populations of European origin). This protective haplotype is at very low frequency in Sub-Saharan Africans (median 0.06) and at intermediate frequencies in other populations (median 0.25). We also revealed, by examining the patterns of linkage disequilibrium around this gene, that the protective haplotype has reached high frequency in non-African populations due to selection acting, most probably, on a linked functional polymorphism, the non-synonymous single nucleotide polymorphism Ser9Gly (rs6280), also at DRD3. Thus, this finding shows that the natural selection may play a role in the existence of common alleles conferring different susceptibility to schizophrenia.

Improving the role of nursing in the treatment of depression in primary care in Spain.

PURPOSE: We describe a multicomponent program for the systematic evaluation and treatment of depression in primary care. CONCLUSION: Primary-care nurses trained in clinical and therapeutic aspects of depression play a central role in care management, patient education, treatment adherence, and clinical monitoring. PRACTICE IMPLICATIONS: Diverse interventions, including organizational changes and the enhancement of the role of nurses, have been effective in improving depression outcomes in primary-care settings.

Structure of personality pathology in normal and clinical samples: Spanish validation of the DAPP-BQ.

Given that the DSM taxonomy of personality disorders is flawed by severe classificatory problems, the development of alternative classificatory systems, such as the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ), has now become a priority. This study examined the internal consistency, second-order factor structure, and criterion validity of a Spanish translation of the DAPP-BQ in two samples: subjects with personality disorder (n = 155) and subjects from the general population (n = 300). Alpha coefficients ranged satisfactorily from .75 to .93. Four second-order factors of Emotional Dysregulation, Dissocial Behavior, Inhibitedness, and Compulsivity were obtained, which were replicable between samples and identical to those reported in the literature. Finally, disordered subjects scored significantly higher than normal subjects on 17 of the 18 DAPP-BQ traits. Some pending issues in the construction of an alternative taxonomy of personality disorders are discussed.

Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia.

Relationships between gender, age-of-onset of schizophrenia and reproductive age strongly suggest a key role for gonadal hormones, and more specifically for estrogens, in the etiology of the illness. Also, estrogens act as neural growth and trophic factors influencing neuron and glial cells in many areas of the central nervous system. Therefore, we investigated the association between schizophrenia and 4 genes related to estrogen metabolism. These genes are ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2), APOE (apolipoprotein E) and COMT (catechol-O-methyltransferase). The expression of APOE and COMT, which contain estrogen response elements, have been demonstrated to be regulated by the estrogen receptors. In this current association study, we examined 59 single nucleotide polymorphisms (SNPs) located in the ESR1 (26), ESR2 (14), APOE (7) and COMT (12) loci. Allele frequencies were evaluated in the schizophrenia (n=585)-control (n=615) sample and no association was found with any of the four genes. In conclusion, our data suggest that the four analyzed genes do not play an important role in susceptibility to schizophrenia.

Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction.

Recent reports indicate that DAO, DAOA, DTNBP1, NRG1 and RGS4 are some of the most-replicated genes implicated in susceptibility to schizophrenia. Also, the functions of these genes could converge in a common pathway of glutamate metabolism. The aim of this study was to evaluate if each of these genes, or their interaction, was associated with schizophrenia. A case-control study was conducted in 589 Spanish patients having a diagnosis of schizophrenia, and compared with 617 equivalent control subjects. Several single nucleotide polymorphisms (SNPs) in each gene were determined in all individuals. SNP and haplotype frequencies were compared between cases and controls. The interaction between different SNPs at the same, or at different gene, loci was analyzed by the multifactor dimensionality reduction (MDR) method. We found a new schizophrenia risk and protective haplotypes in intron VII of DTNBP1; one of the most important candidate genes for this disorder, to-date. However, no association was found between DAO, DAOA, NRG1 and RGS4 and schizophrenia. The hypothesis that gene-gene interaction in these five genes could increase the risk for the disorder was not confirmed in the present study. In summary, these results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia, but not between the disease and DAO, DAOA, NRG1 and RGS4 or with the interaction of these genes. In the light of recent data, these results need to be interpreted with caution and future analyses with dense genetic maps are awaited.

Assessment of an enhanced program for depression management in primary care: a cluster randomized controlled trial. The INDI project (Interventions for Depression Improvement).

BACKGROUND: Most depressed patients are attended at primary care. However, there are significant shortcomings in the diagnosis, management and outcomes of these patients. The aim of this study is to determine whether the implementation of a structured programme for managing depression will provide better health outcomes than usual management. DESIGN: A cluster-randomized controlled trial involving two groups, one of which is the control group consisting of patients who are treated for depression in the usual way and the other is the intervention group consisting of patients on a structured programme for treating depression. SETTING: 20 primary care centres in the province of Tarragona (Spain) SAMPLE: 400 patients over 18 years of age who have experienced an episode of major depression (DSM-IV) and who need to initiate antidepressant treatment INTERVENTION: A multi-component programme with clinical, educational and organisational procedures that includes training for the health care provider and evidence-based clinical guidelines. It also includes primary care nurses working as care-managers who provide educational and emotional support for the patients and who are responsible for active and systematic clinical monitoring. The programme aims to improve the primary care/specialized level interface. MEASUREMENTS: The patients will be monitored by telephone interviews. The interviewer will not know which group the patient belongs to (blind trial). These interviews will be given at 0, 3, 6 and 12 months. MAIN VARIABLES: Severity of the depressive symptoms, response rate and remission rate. ANALYSIS: Outcomes will be analyzed on an intent-to-treat basis and the unit of analysis will be the individual patient. This analysis will take into account the effect of study design on potential lack of independence between observations within the same cluster. DISCUSSION: The effectiveness of caring for depression in primary care can be improved by various strategies. The most effective models involve organisational changes and a greater role of nurses. However, these models are almost exclusively from the USA, and this randomized clinical trial will determine if this approach could be effective to improve the outcomes of depression in primary care in the Spanish health care system. TRIAL REGISTRATION: ISRCTN16384353.

Depression and physical comorbidity in primary care.

OBJECTIVE: To analyse how clinical characteristics in depressed patients, as well as the management of their depression, are related to the presence of significant physical comorbidity. METHODS: This is a two-phase cross-sectional study that took place in 10 primary care centres in Tarragona (Spain). A total of 906 consecutive patients were screened for depression with a self-rating questionnaire and 306 were subject to a structured interview that contained the diagnoses of major depression and dysthymia (DSM-IV), and the severity of the physical comorbidity (Duke Severity of Illness Scale: DUSOI). The association of several clinical variables with the presence of physical comorbidity was evaluated. RESULTS: The comorbidity was of moderate to extreme severity (DUSOI >50) in 31.7% of cases. The patients with comorbidity visited the physician more often. There were no differences in the consumption of antidepressants, reason for the consultation (psychological/somatic), or the probability of being detected as depressed. Neither were there any differences in the severity or disability between both groups. CONCLUSION: Physical comorbidity is frequent in primary care depressed patients. In general, the characteristics of depression and the handling by the doctor are similar in patients with and without comorbidity.

M129V variation in the prion protein gene and psychotic disorders: relationship to neuropsychological and psychopathological measures.

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.

New variants in the mitochondrial genomes of schizophrenic patients.

The impaired mitochondrial function hypothesis in schizophrenia is based on evidence of altered brain metabolism, morphology, biochemistry and gene expression. Mitochondria have their own genome, which is needed to synthesize some of the subunits of the respiratory chain enzymes. Mitochondrial DNA (mtDNA) is maternally inherited and we observed an excess of maternal transmission of schizophrenia in a set of parent-offspring affected pairs. We therefore hypothesized that mutations in the mtDNA may contribute to the complex genetic basis of schizophrenia. The entire mtDNA of six schizophrenic patients with an apparent maternal transmission of the disease was sequenced and compared to the reference sequence. We have identified 50 variants and among these six have not been previously reported. Three of them were missense variants: MTCO2 7750C>A, MTATP6 8857G>A and MTND4 12096T>A. These were maternally inherited because they were also present in the mtDNA of their respective schizophrenic mothers and none of them were found in 95 control individuals. The MTND4 12096T>A (Leu446His) is a heteroplasmic variant present in five of the six mother-offspring patient pairs that triggers a non-conservative substitution in the ND4 subunit of complex I. Sequence alignment of 110 ND4 peptides from all eukaryotic kingdoms shows that only hydrophobic amino acids are found in this position. Moreover, leucine was conserved or substituted by an isoleucine in all mammalian species. This indicates that the presence of histidine could affect complex I activity in patients with schizophrenia.

The overdiagnosis of depression in non-depressed patients in primary care.

BACKGROUND: The underdiagnosis of depression is an important research topic. Nevertheless, overdiagnosis has not been given the importance it deserves by research into the ability of family physicians to diagnose depression correctly. OBJECTIVES: To identify the factors that determine the overdiagnosis of depression by family physicians and to evaluate the clinical significance of this error. DESIGN: Two-phase cross-sectional study. SETTING: Primary care centres in Tarragona (Spain). METHODS: In the first phase, we screened 906 consecutive patients using Zung's self-rating depression scale (SDS). In the second phase, all the 209 patients with a positive screening and 97 patients with a negative screening (1 out of 7 randomly) were given the Structured Clinical Interview for DSM-IV Disorders, a series of questionnaires, and the family physician judged whether depression was present. In the 186 patients for whom there were no criteria of major depression or dysthymia, the association of various variables with the physicians' overdiagnosis of depression was analysed. RESULTS: The rate of diagnosis of depression in non-depressed patients was 26.5% (95% CI: 19.0-33.9). The factors associated independently with overdiagnosis were the SDS score (OR: 1.05; 95% CI: 1.01-1.10), the Global Assessment of Functioning score (OR: 0.95; 95% CI: 0.90-0.99), previous history of depression (OR: 2.66; 95% CI: 1.12-6.30) and presence of generalized anxiety (OR: 0.42; 95% CI: 0.18-0.97). CONCLUSION: Family physicians classify as depressed those patients who do not have the formal signs of depression but who do have antecedents of this disorder or a psychological distress that may be prodromal of future depressive episodes.