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Adverse childhood experiences, including child maltreatment (CM), are relevant environmental risk factors for bipolar disorder (BD). However, little is known about the interaction of the type, duration and frequency of abuse with the timing of abuse in BD. The aim of this study was to investigate the different patterns of childhood trauma (frequency, type and chronology) between BD patients and healthy controls (HCs) and to identify BD-sensitive periods of exposure to CM that could influence functioning outcomes. The Maltreatment and Abuse Chronology Exposure (MACE) scale was used to evaluate the importance of the type and timing of maltreatment in a sample of 60 patients diagnosed with euthymic BD. Additionally, 76 HCs were recruited for comparison. All participants were of European-Caucasian origin and were assessed in the 2016-2019 period. To identify the variables that maximally differentiated the type and timing of exposure to CM between the BD and HC groups, a linear mixed effects model and random forest (RF) analyses were applied. We showed that multiplicity and severity, nonverbal emotional abuse, witnessing interparental violence and emotional neglect were the main factors associated with BD. In addition, regarding the occurrence of maltreatment in BD patients, we identified two sensitive periods with a principal peak at the age of 6 and a secondary peak at the age of 11. Functionality at the assessment time was associated with CM in adolescence for both HC and BD participants. Although the sample size and retrospective nature of the MACE instrument were the main limitations of our study, we were unable to explore the role of variables such as sex or socioeconomic status. We concluded that the multiplicity and sensitivity of CM exposure, mainly of the emotional type, during middle childhood are important risk factors for BD, at least in the European-Caucasian cultural setting.

Abstract: Current dimensional taxonomies of personality disorder (PD) establish that intense traits do not suffice to diagnose a disorder, and additional constructs reflecting dysfunction are required. However, traits appear able to predict maladaptation by themselves, which might avoid duplications and simplify diagnosis. On the other hand, if trait-based diagnoses are feasible, it is the whole personality profile that should be considered, rather than individual traits. This takes us into multidimensional spaces, which have their own particular – but poorly understood – logic. The present study examines how profile-level differences between normal and disordered subjects can be used for diagnosis. The Dimensional Assessment of Personality Pathology – Basic Questionnaire (DAPP-BQ) and the Personality Inventory for DSM-5 (PID-5) were administered to a community and a clinical sample each (total n = 1,925 and 3,543 respectively). Intense traits proved to be common in the general population, so empirically-based thresholds are indispensable not to take as abnormal what is at most unideal. Profile-level parameters such as Euclidean and Mahalanobis distances outperformed individual traits in predicting mental problems and equaled the performance of published measures of dysfunction or severity. Personality profiles can play a more central role in identifying disorders than is currently acknowledged, provided that adequate metrics are used.

Although normal personality traits change gradually with age, personality disorders have been reported to remit rapidly and completely in little more than 10 years. Such a benign prognosis is surprising and may be due in part to the combined use of categorical diagnoses, seriously ill patients, and longitudinal designs in the existing literature. This study examines, for the first time, the development of personality pathology across a life span by means of dimensional models, represented by the Dimensional Assessment of Personality Pathology-Basic Questionnaire and the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. We draw upon a cross-sectional design and four large clinical and community samples to avoid previous biases. We found that personality pathology declined by around 0.5 SD overall from age 20 to 60, though with noticeable differences between domains: Dissocial behavior and antagonism decreased by between two thirds and 1 SD; compulsivity increased at the same rate; disinhibition, negative affect, and psychoticism dropped by 0.5 SD; and detachment remained stable or rose slightly. In short, the changes in many clinically important traits are modest, occur at a slow pace, and roughly parallel the maturation effect found for normal personality traits. The resulting picture of personality disorder development is not as optimistic as previous studies would have us believe. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Resumen Introduccion El maltrato infantil se ha asociado a un mayor riesgo de psicosis, a una mayor severidad en sintomas psicopatologicos y a un peor pronostico funcional en pacientes con un trastorno psicotico. El presente estudio pretende evaluar la relacion entre el maltrato infantil, psicopatologia y la adaptacion social en una muestra de primeros episodios psicoticos (PEP) y de estados mentales de alto riesgo (EMAR). Material y metodos La muestra incluyo 114 jovenes (18-35 anos, 81 PEP y 33 EMAR) atendidos en un Servicio de Intervencion Precoz en Psicosis. Se evaluaron sintomas positivos, negativos y depresivos con las escalas PANSS y Calgary de Depresion; los antecedentes de maltrato infantil con el Childhood Trauma Questionnaire; la adaptacion social con la Escala Autoaplicada de Adaptacion Social (SASS). Se utilizo el modelo de ecuaciones estructurales (SEM) para explorar relaciones entre psicopatologia, maltrato infantil y dimensiones de la SASS en toda la muestra (incluyendo PEP y EMAR). Se repitio un analisis SEM exploratorio en la submuestra de PEP. Resultados Los EMAR presentaron mas negligencia emocional y peor adaptacion social, comparados con los PEP. El SEM muestra que el maltrato se asocia con una peor adaptacion social en todos los dominios, de forma directa en dominios que implican relaciones interpersonales, y por una via mediada por sintomas depresivos en los dominios que implican ocio y trabajo e intereses socioculturales. Conclusiones El maltrato infantil tiene un efecto negativo sobre la adaptacion social en jovenes en fases tempranas de las psicosis. Los sintomas depresivos son mediadores de una peor adaptacion en aspectos funcionales relacionados con el ocio y el trabajo.

Introduction Childhood trauma has been associated with an increased risk of psychosis, a greater severity of psychopathological symptoms, and a worse functional prognosis in patients with psychotic disorders. The current study aims to explore the relationship between childhood trauma, psychopathology and social adaptation in a sample of young people with first episode psychosis (FEP) or at-risk mental states (ARMS). Material and methods The sample included 114 young people (18–35 years old, 81 FEP and 33 ARMS) who were attending an Early Intervention Service for Psychosis. Positive, negative and depressive symptoms were assessed with the PANSS and the Calgary Depression Scale; history of childhood trauma was assessed with the Childhood Trauma Questionnaire; social adaptation was assessed with the Social Adaptation Self-evaluation Scale (SASS). Structural equation modelling (SEM) was used to explore the relationship between childhood trauma, psychopathology and SASS dimensions in the global sample (including FEP and ARMS). An exploratory SEM analysis was repeated in the subsample of FEP patients. Results ARMS individuals reported more emotional neglect and worse social adaptation compared to FEP. SEM analysis showed that childhood trauma is associated with a worse social adaptation, in a direct way with domains involving interpersonal relationships, and mediated by depressive symptoms with those domains involving leisure, work and socio-cultural interests. Conclusions Childhood trauma has a negative effect on social adaptation in young people with early psychosis. Depressive symptoms play a mediation role in this association, especially in domains of leisure and work.

Deficits in social cognition and metacognition impact the course of psychosis. Gender differences in social cognition and metacognition could explain heterogeneity in psychosis. 174 (58 females) patients with first-episode psychosis completed a clinical, neuropsychological, social cognitive and metacognitive assessment. Subsequent latent profile analysis split by gender yielded 2 clusters common to both genders, a specific male profile characterized by presenting jumping to conclusions and a specific female profile characterized by cognitive biases. Males and females in the homogeneous profile seem to have a more benign course of illness. Males with jumping to conclusions had more clinical symptoms and more neuropsychological deficits. Females with cognitive biases were younger and had less self-esteem. These results suggest that males and females may benefit from specific targeted treatment and highlights the need to consider gender when planning interventions.

Aim: To investigate DDR1 methylation in blood and brain DNA in psychosis and its relationship with stress markers. Materials & methods: Saliva cortisol, blood neutrophil and lymphocyte counts, leukocyte DNA and psychological variables were collected from 60 patients with nonaffective psychosis and 40 healthy controls (HC). Brain dorsolateral prefrontal cortex DNA from 35 patients with schizophrenia and 34 HC was studied. DDR1 methylation at 43 CpG sites was measured using the MassARRAY EpiTYPER platform. Results: We describe leukocyte DDR1 hypermethylation in patients with psychosis compared with HC; this hypermethylation is associated with psychological stress, neutrophil-to-lymphocyte ratios, and, in the dorsolateral prefrontal cortex, DDR1 methylation correlated with DDR1 isoform expression. Conclusion: We confirmed a relationship between stress and blood and brain DDR1 methylation in psychosis.

Smoking prevalence in schizophrenia is considerably larger than in general population, playing an important role in early mortality. We compared the polygenic contribution to smoking in schizophrenic patients and controls to assess if genetic factors may explain the different prevalence. Polygenic risk scores (PRSs) for smoking initiation and four genetically correlated traits were calculated in 1108 schizophrenic patients (64.4% smokers) and 1584 controls (31.1% smokers). PRSs for smoking initiation, educational attainment, body mass index and age at first birth were associated with smoking in patients and controls, explaining a similar percentage of variance in both groups. Attention-deficit hyperactivity disorder (ADHD) PRS was associated with smoking only in schizophrenia. This association remained significant after adjustment by psychiatric cross-disorder PRS. A PRS combining all the traits was more explanative than smoking initiation PRS alone, indicating that genetic susceptibility to the other traits plays an additional role in smoking behaviour. Smoking initiation PRS was also associated with schizophrenia in the whole sample, but the significance was lost after adjustment for smoking status. This same pattern was observed in the analysis of specific SNPs at the CHRNA5-CHRNA3-CHRNB4 cluster associated with both traits. Overall, the results indicate that the same genetic factors are involved in smoking susceptibility in schizophrenia and in general population and are compatible with smoking acting, directly or indirectly, as a risk factor for schizophrenia that contributes to the high prevalence of smoking in these patients. The contrasting results for ADHD PRS may be related to higher ADHD symptomatology in schizophrenic patients.

The International Classification of Diseases–11th revision (ICD-11) classification of personality disorders is the official diagnostic system that is used all over the world, and it has recently been renewed. However, as yet very few data are available on its performance. This study examines the Personality Inventory for ICD-11 (PiCD), which assesses the personality domains of the system, and the Standardized Assessment of Severity of Personality Disorder (SASPD), which determines severity. The Spanish versions of the questionnaires were administered to a community (n = 2,522) and a clinical sample (n = 797). Internal consistency was adequate in the PiCD (α =.75 to.84) but less so in the SASPD (α =.64 and.73). Factor analyses suggested a unidimensional or bidimensional structure for severity, while revealing that the personality trait qualifiers are organized into four factors: negative affectivity, detachment, dissociality, and a bipolar domain of disinhibition–anankastia. The mutual relationships between traits and severity were analyzed, as well as the ability of the whole system to identify clinical subjects. Although further improvements are required, the results generally support the use of the PiCD and the SASPD and help substantiate the new ICD-11 taxonomy that underlies them., This work was supported by project PI15/00536, part of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, financed by the ISCIII Subdirección General de Evaluación and the cofinanced by the European Regional Development Fund (ERDF, “A way to build Europe”; PI: F. Gutiérrez)

Cognitive impairment has been associated with both childhood adversity and abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function. An interaction exists between the functional polymorphism rs1360780 in the FKBP5 gene and childhood maltreatment, influencing a variety of clinical outcomes. Our goal was to study the relationship between different types of childhood trauma, HPA axis functionality, rs1360780 genotype and cognitive function in 198 healthy individuals who participated in the study. We obtained clinical data, childhood maltreatment scores and neurocognitive performance by clinical assessment; HPA negative feedback was analysed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone; and the FKBP5 rs1360780 polymorphism was genotyped in DNA obtained from blood samples. The results showed a significant influence of physical neglect on measures of neurocognition as well as an interaction between the DSTR and physical and emotional neglect. Regarding social cognition, a significant association was found with sexual and physical abuse as well as with rs1360780 risk-allele carrier status. Moreover, an interaction between the rs1360780 genotype and the presence of physical abuse was significantly associated with social cognition results. Our results suggest a specific impact of different kinds of childhood maltreatment on measures of neurocognition and social cognition, which might be influenced by HPA axis reactivity and genetic variants in HPA axis-related genes such as FKBP5. Disentangling the relationship between these elements and their influence on cognitive performance might help identify susceptible individuals with higher stress vulnerability and develop preventive interventions.

Background:Borderline personality disorder (BPD) usually begins in adolescence and manifests itself in adult life. Early intervention can improve the prognosis or reduce its severity. Nevertheless, there are currently few studies of adolescent patients with severe emotion instability and borderline personality traits.Aims:To evaluate the effectiveness of the Systems Training for Emotional Predictability and Problem Solving (STEPPS) programme in a sample of 21 adolescents (aged 13–17 years) in the Child and Adolescents Mental Health Center of Tarragona in Spain.Method:We evaluated BPD traits using the Diagnostic Interview for Borderline Disorder-Revised (DIB-R) and the Global Clinical Impression Scale of Illness Severity for TLP (CGI-TLP). We compared pre- and post-treatment scores for the DIB-R, CGI-GI scale, general psychopathology using the Personality Inventory for Adolescents (PAI-A) and impulsivity with the Barratt Impulsivity Scale (BIS-11). The therapeutic objectives were evaluated with the Borderline Estimate Severity over Time (BEST) scale.Results:There was a statistically significant improvement in the scores for the affective area and in the total score of the DIB-R, a decrease in the percentage of patients who failed to meet criteria for BPD, and an improvement (although not statistically significant) in the scores of the BEST scale throughout the treatment. The results of the CGI-GI scale showed global improvement in almost 72% of patients.Conclusion:Our study suggests that STEPPS can be an effective treatment to improve BPD symptoms and is very useful in community settings with limited resources in which efficient treatment alternatives must be sought. However, this conclusion must be interpreted with caution, as there is no comparison control group.

Metacognitive training (MCT) improves cognitive biases in psychosis. We aimed to explore whether the effectiveness of the combination of psychoeducation and MCT group treatments on cognitive biases differed if the combination was started by psychoeducation or by MCT. Fourty-nine stable patients with a recent-onset psychosis were randomized to two different sequences: MCT + psychoeducation vs psychoeducation + MCT. Cognitive biases, psychopathology symptoms, insight and functioning were assessed. Cognitive biases and depressive symptoms improved with both group interventions, without differential effects between both sequences. Our study suggests that MCT and psychoeducation are useful in improving cognitive biases and depressive symptoms in recent-onset psychosis.

The Autism Spectrum Disorders - Diagnosis for Adults (ASD-DA) with intellectual disability was designed to quickly provide relevant information to establish a diagnosis of the most common Autism Spectrum Disorders (ASD) (autism, pervasive developmental disorder not otherwise specified and Asperger's syndrome) (Matson et al. 2007a). The ASD-DA was adapted and translated into Spanish and administered to a sample of 156 adults with severe (n = 67, 42.9%) and profound (n = 89, 57.1%) intellectual disability. Seventy-one (45.5%) participants had a diagnosis of intellectual disability and autism spectrum disorder, and the other eighty-five (54.5%) had a diagnosis of intellectual disability without autism spectrum disorder. The reliability scores of the scales implied values in the "good-to-excellent" range (0.78-0.95), and test-retest reliability was obtained with good values for most of the items on the scale. A three-factor structure was replicated via confirmatory factor analysis. Participants with and without ASD showed significant differences in the three ASD-DA scales and in their total scores. Using a receiver operating characteristics (ROC) curve, a score of 21 on the ASD-DA scale showed good specificity (0.97) and sensitivity (0.92) values with respect to DSM-IV-TR criteria.

Background The individual Metacognitive Training (MCT+) is useful to reduce positive symptoms in people with schizophrenia, however less is known in people with first-episode psychosis (FEP). The aim of the study is to assess the effectiveness of MCT+ in FEP regarding symptoms and cognitive insight. Methods A random clinical trial was performed with people with FEP from 10 clinical centers of Spain. One group received ten sessions of MCT+ and the other group received TAU. A total of 75 patients were included in the study, however only 40 finished the final assessment. Patients were assessed before treatment, post-treatment and 6 month follow-up. The assessment includes a battery of instruments for the main aims the Positive and Negative Syndrome Scale (PANSS) and the Beck Cognitive Insight (BCIS) will be analyzed. Repeated measures statistical test were used in order to assess differences between groups. Results Both groups improved in Positive symptoms, in the MCT+ group the difference was 5.18 (SD=6.8) with a significance of p=0.002, while in the TAU group the difference was 3.38 (SD=4.9) with a significance of p=0.005. Regarding cognitive insight, in the MCT+ group patients improved in Self-reflectiveness, obtaining a score in baseline of 15.21 (SD=5.52) and 18 (SD=5.28) in post-treatment (p=0.017). The TAU group did not improve in any subscale of the BCIS. Discussion The MCT+ seems to improve more in positive symptoms than TAU, although both interventions diminished the presence of these symptoms. The MCT+ improved the self-reflectiveness, being one of the important areas for the understanding of the daily social functioning in relation to other. Further analysis should be explored.

Suicidability has been associated with neuroticism and psychoticism, but its role during perinatal period has not been analyzed. We explore the association between personality dimensions, depressive symptoms, and other psychosocial variables in postpartum suicidal ideation. A cohort of 1795 healthy Spanish women from the general population was assessed for suicidal ideation (EPDS-Item10) in early postpartum, 8 and 32 weeks postpartum. Sociodemographic, obstetric, and reproductive variables, psychiatric history, social support, stressful life-events during pregnancy, depressive symptoms (EPDS), and the Eysenck's personality dimensions (EPQ-RS) were also assessed at baseline. A major depressive episode (DSM-IV) was confirmed in women with EPDS>10 at follow-up assessments. Descriptive, bivariate, and multivariate analyses were conducted. Adjusted logistic regression analysis was reported as odds ratio (ORs) with 95% confidence intervals (CIs). Seven percent of mothers reported suicidal ideation during the first 8 months postpartum. Sixty-two percent of women with suicidal ideation had a major depressive episode at 8 weeks, and 70% at 32 weeks postpartum. Neuroticism and psychoticism predicted suicidal ideation throughout the first 2 weeks after delivery (OR, 1.03; 95%CI 1.01-1.06; and OR, 1.03; 95%CI 1.01-1.05 respectively). Early postpartum depressive symptoms (OR 1.2; 95%CI 1.11-1.26), personal psychiatric history (OR 2.1; 95%CI 1.33-3.27), and stressful life events during pregnancy (OR 1.88; 95%CI 1.12-3.16) also emerged as predictors of postpartum suicidal ideation. Analysis of women for postpartum suicidal ideation should include not only psychiatric symptoms but also psychosocial assessment (i.e., covering psychiatric history, stressful events, or long-standing personality vulnerabilities) in order to identify those in need of early psychosocial or psychiatric care.

The results of previous cross-sectional studies suggest that free thyroxine (FT4) levels are associated with cognitive abilities (particularly attention/vigilance) during the early stages of psychosis. We aimed to explore whether hypothalamic-pituitary-thyroid hormones predict cognitive changes in a 1-year longitudinal study following first episodes of psychosis (FEP). We studied 36 FEP patients and a control group of 50 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH) and FT4 were measured. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery (MCCB). FEP patients were assessed twice (baseline and after 1year), whereas HS were assessed only once. We compared cognitive changes at 1year between three groups based on baseline FT4 levels: 1) lowest quartile (Q1, FT41.16ng/dL); 2) medium quartiles (Q2-Q3, FT4 1.16-1.54ng/dL); and 3) highest quartile (Q4, FT41.54ng/dL). No differences in TSH or FT4 levels were found between HS and FEP patients. All participants had FT4 levels within the normal range. HS outperformed FEP patients in all cognitive tasks. In relation to the relationship between FT4 levels and cognitive changes, a U-shaped pattern was observed: FEP patients from the middle quartiles (Q2-Q3) improved in attention/vigilance, whereas both extreme quartiles (Q1 and Q4) showed a worsening in this cognitive domain over time. Patients with lower FT4 (Q1) showed poorer baseline attention; therefore, lower baseline FT4 levels predicted a poorer prognosis in terms of attention performance. Our study suggests that baseline FT4 levels are associated with changes in attention and vigilance performance over one year in FEP patients.

Background Previous studies have shown associations between obsessive-compulsive disorder (OCD) and hypothalamic-pituitary-adrenal axis activity (HPA). We aimed to investigate the association between obsessive-compulsive (OC) symptoms and HPA axis functionality in a non-clinical sample and to explore whether there are sex differences in this relationship. Methods One hundred eighty-three healthy individuals without any psychiatric diagnosis (80 men, 103 women; mean age 41.3 ± 17.9 years) were recruited from the general population. The Obsessive-Compulsive Inventory Revised (OCI-R) was used to assess OC symptoms. State-trait anxiety, perceived stress, and stressful life events were also assessed. Saliva cortisol levels were determined at 6 time points (awakening, 30 and 60 min post-awakening, 10:00 a.m., 23:00 p.m. and 10:00 a.m. the following day of 0.25 mg dexamethasone intake [that occurred at 23:00 p.m.]). Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope, and cortisol suppression ratio after dexamethasone (DSTR). Multiple linear regression analyses were used to explore the association between OC symptoms and HPA axis measures while adjusting for covariates. Our main analyses were focused on OCI-R total score, but we also explored associations with specific OC symptom dimensions. Results No significant differences were observed between males and females in OC symptoms, anxiety measures, stress, or cortisol measures. In the multiple linear regression analyses between overall OC symptoms and HPA axis measures, a female sex by OC symptoms significant interaction (standardized beta = − 0.322; p = 0.023) for the CAR (but not cortisol diurnal slope nor DSTR) was found. Regarding specific symptom dimensions, two other sex interactions were found: a blunted CAR was associated with obsessing symptoms in women, whereas a more flattened diurnal cortisol slope was associated with ordering symptoms in men. Conclusions There are sex differences in the association between OC symptoms and HPA axis measures in healthy individuals.

Postpartum depression (PPD) is a common mood disorder that occurs after delivery with a prevalence of approximately 10%. Recent reports have related placental corticotropin-releasing hormone (pCRH) to postpartum depressive symptoms. The aim of this study was to determine whether pCRH, ACTH, and cortisol (measured 48 h after delivery) and glucocorticoid and mineralocorticoid receptor genotypes (NR3C1 and NR3C2) and their interaction are associated with PPD. A longitudinal 32-week prospective study of five hundred twenty-five Caucasian depression-free women that were recruited from obstetric units at two Spanish general hospitals immediately after delivery. Of the women included in the sample, forty-two (8%) developed PPD. A strong association between PPD and the interaction between the pCRH and NR3C2 rs2070951 genotype was observed. The mean level of pCRH in rs2070951GG carriers with PPD was 56% higher than the mean in the CG and CC genotype groups (P

Subjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic-pituitary-thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis.We studied 70 patients with a psychotic disorder (3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder).In patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis.Our study suggests that FT4 levels are associated with cognitive abilities (attention/vigilance and overall cognition) in individuals with early psychosis.

Hypothalamic-pituitary-adrenal (HPA) axis alterations in at-risk mental states (ARMS) resemble those observed in established psychosis but are less consistent. We aimed to explore HPA axis abnormalities in both first-episode psychosis (FEP) and ARMS patients, while controlling for psychopathological symptoms. We studied 21 ARMS, 34 FEP patients and 34 healthy subjects. Clinical assessment included psychopathological symptoms (positive, negative, disorganized, excited and depressive symptoms) and stress measures. Saliva cortisol levels were determined at awakening, 30' and 60' post-awakening, 10:00 h, 23:00 h and 10:00 h on the day after the administration of 0.25 mg of dexamethasone, which occurred at 23:00 h. Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). There were no significant differences between groups in HPA axis measures. However, when exploring the relationship between HPA axis measures and psychopathological symptoms, in ARMS subjects (but not FEP patients), a flatter cortisol slope was associated with more prominent negative symptoms, whereas a blunted CAR was associated with excited symptoms. Although no significant differences in HPA axis measures were found between diagnostic groups, subtle abnormalities in the CAR or circadian cortisol rhythmicity might be important for the phenotype of ARMS individuals.

Background Group psychotherapeutic treatments can improve negative symptoms and social functioning deficits in the treatment of schizophrenia. These treatments may include different modalities including group cognitive behavioral therapy, psychoeducation and metacognitive training (MCT). MCT is effective for preventing delusions by modifying the cognitive biases most related to psychosis. Our primary goal was to address whether cognitive biases improve more specifically with MCT when compared to psychoeducation in a sample of patients with recent onset psychosis. Methods Design: a multicenter randomized, pilot clinical trial was performed, in which one group received psychoeducation and the other MCT. Sample 49 patients aged between 18–35 years and with a diagnosis of psychotic disorder according to DSM-IV-TR criteria and less than 3 years of duration of illness. All patients were recruited at two Early Psychosis Programmes in Spain (ParcTaulí Hospital Universitari, Sabadell; Hospital UniversitariInstitut Pere Mata, Reus). Ethical approval was obtained from the local Ethics Committees of both institutions. Outcomes Patients were evaluated at baseline and at the end of each intervention. The primary outcome was cognitive biases, assessed with Cognitive Biases Questionnaire for Psychosis (CBQ). Secondary outcomes included cognitive insight, psychopathological symptoms (positive, negative, depressive) and psychosocial functioning. Interventions The interventions consisted of 8 weekly group sessions of MCT (developed at the University of Hamburg-Eppendorf by Steffen Moritz) or psychoeducation. MCT program included sessions dealing with attributional style, jumping to conclusions, changing beliefs, empathy, memory, and depression and self-esteem. The psychoeducational program included sessions addressing aspects related to psychotic illness (psychotic symptoms, risk factors of relapse, stress management, psychopharmacological treatment, substance use, physical health and social skills). Statistical analysis: A general linear model for repeated measures was performed in order to compare the longitudinal effect of the intervention and to test whether changes in outcome variables differed by treatment group. All analyses were adjusted for gender. A p value < 0.05 (two-tailed) was considered to be significant. Results Of all 49 patients, 38 (77.6%) completed at least 50% of the sessions, and were included in the final analyses. 21 received psychoeducation and 16 MCT. Cognitive biases improved significantly in both psychoeducation (43.8 ± 11.2 vs 40.8 ± 10.4) and MCT groups (44.2 ± 7.6 vs 39.6 ± 5.0). The time effect was significant (F= 18.9, p

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.

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).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 frequency5% 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.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.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.

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.

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.

Resumen Introduccion El objetivo del estudio fue adaptar y validar en castellano la Escala Pronostica para la Esquizofrenia de Strauss y Carpenter (Strauss y Carpenter, 1977). Metodo Se trata de un estudio multicentrico, longitudinal y descriptivo. Se realizo una traduccion y una retrotraduccion de la escala. La muestra se compuso de sujetos de 18-65 anos diagnosticados de esquizofrenia. Se calculo la fiabilidad entre evaluadores, la validez de constructo con las escalas EEAG, SLDS, ICG, WHO-DAS y PANSS, y la validez predictiva respecto a 3 variables criterio al ano medidas con las escalas ICG, EEAG y WHO-DAS. Resultados El coeficiente de consistencia interna (alfa de Cronbach) fue 0,70. El coeficiente de correlacion intraclase oscilo entre 0,54 y 0,99, excepto en el item 5 (Recursos para el tratamiento utilizados actualmente), que fue −0,13. Respecto a la validez de constructo, la correlacion fue significativa entre las diferentes escalas, con una p Conclusiones La adaptacion espanola de la escala pronostica de esquizofrenia de Strauss-Carpenter es fiable, valida y permite predecir un curso deteriorado de la enfermedad.

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.

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.

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.

Childhood trauma, a risk factor of psychosis, is associated the clinical expression of the illness (greater severity of psychotic symptoms; poorer cognitive performance). We aimed to explore whether there are sex differences in this relationship. We studied 79 individuals with a psychotic disorder (PD) with < 3 years of illness and 59 healthy subjects (HS). All participants were administered the MATRICS Cognitive Consensus Cognitive Battery (MCCB) to assess cognition. Depressive, positive and negative psychotic symptoms, and global functioning were also assessed. History of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Patients reported a greater history of childhood trauma on all CTQ domains (emotional, physical and sexual abuse, and physical and emotional neglect). A poorer cognitive performance was also observed in PD when compared to HS. No sex differences were found in the CTQ scores. In the relationship between childhood trauma and psychopathological symptoms, significant correlations were found between CTQ scores and positive and negative psychotic symptoms, depressive symptoms and poorer functionality, but only in women. Childhood trauma was associated with poorer social cognition in both men and women. Of all CTQ dimensions, emotional neglect and physical neglect were more clearly associated with a more severe psychopathological and cognitive profile. Our results suggest that childhood trauma, particularly emotional and physical neglect, is associated with the clinical expression of psychosis and that there are sex differences in this relationship.

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.

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2–3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04–1.33), substance use (OR 0.58, 95 % CI 0.35–0.97), and self-blame (OR 1.18, 95 % CI 1.04–1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

Objectives.The psychometric properties regarding sex and age for the revised version of the Temperament and Character Inventory (TCI-R) and its derived short version, the Temperament and Character Inventory (TCI-140), were evaluated with a randomized sample from the community.Methods.A randomized sample of 367 normal adult subjects from a Spanish municipality, who were representative of the general population based on sex and age, participated in the current study. Descriptive statistics and internal consistency according toαcoefficient were obtained for all of the dimensions and facets.T-tests and univariate analyses of variance, followed by Bonferroni tests, were conducted to compare the distributions of the TCI-R dimension scores by age and sex.Results.On both the TCI-R and TCI-140, women had higher scores for Harm Avoidance, Reward Dependence and Cooperativeness than men, whereas men had higher scores for Persistence. Age correlated negatively with Novelty Seeking, Reward Dependence and Cooperativeness and positively with Harm Avoidance and Self-transcendence. Young subjects between 18 and 35 years had higher scores than older subjects in NS and RD. Subjects between 51 and 77 years scored higher in both HA and ST. The alphas for the dimensions were between 0.74 and 0.87 for the TCI-R and between 0.63 and 0.83 for the TCI-140.Conclusion.Results, which were obtained with a randomized sample, suggest that there are specific distributions of personality traits by sex and age. Overall, both the TCI-R and the abbreviated TCI-140 were reliable in the ‘good-to-excellent’ range. A strength of the current study is the representativeness of the sample.