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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.

We assessed the utility of raloxifene (60 mg/day) as an adjuvant treatment for cognitive symptoms in postmenopausal women with schizophrenia in a 24-week, double-blind, randomized, placebo-controlled study. Patients were recruited from the inpatient and outpatient services of Parc Sanitari Sant Joan de Deu, Hospital Universitari Institut Pere Mata, and Corporacio Sanitaria Parc Tauli. Seventy eight postmenopausal women with schizophrenia were randomized to either adjunctive raloxifene or placebo. Sixty-eight began the clinical trial (37 women on raloxifene adjunct) and 31 on placebo adjunct. The outcome measures were: memory, attention and executive function. Assessment was conducted at baseline and at week 24. Between groups homogeneity was tested with the Student's t test for continuous variables and/or the Mann–Whitney U test for ordinal variables and the χ2 test or Fisher's exact test for categorical variables. The differences between the two groups in neuropsychological test scores were compared using the Student's t test. The sample was homogenous with respect to age, formal education, illness duration and previous pharmacological treatment. The addition of raloxifene to antipsychotic treatment as usual showed no differences in cognitive function. The daily use of 60 mg raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia has no appreciable effect. ClinicalTrials.gov Identifier: NCT01573637.

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.

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.

The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Deu, Hospital Universitari Institut Pere Mata, and Corporacio Sanitaria Parc Tauli. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a larger sample and a longer follow-up. Trial registration: {"type":"clinical-trial","attrs":{"text":"NCT01573637","term_id":"NCT01573637"}}NCT01573637.

The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized. Raloxifene, a selective estrogen receptor modulator, appears to act similarly to estrogens on dopamine and serotonin brain systems. One previous trial by our team found that raloxifene was useful to improve negative, positive, and general psychopathological symptoms, without having the negative side effects of estrogens. In this study, we assess the utility of raloxifene in treating negative and other psychotic symptoms in postmenopausal women with schizophrenia exhibiting prominent negative symptoms. This was a 24-week, randomized, parallel, double-blind, placebo-controlled study. Patients were recruited from the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu, Hospital Universitari Institut Pere Mata, and Corporació Sanitària Parc Taulí. Seventy postmenopausal women with schizophrenia (DSM-IV) were randomized to either adjunctive raloxifene (38 women) or adjunctive placebo (32 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). The addition of raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced negative (P = .027), general (P = .003), and total symptomatology (P = .005) measured with the PANSS during the 24-week trial, as compared to women receiving placebo. Also Alogia SANSS subscale improved more in the raloxifene (P = .048) than the placebo group. In conclusion, raloxifene improved negative and general psychopathological symptoms, compared with antipsychotic medication alone, in postmenopausal women with schizophrenia. These data replicate our previous results with a lar

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.

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.

We studied the clinical correlates of obsessive-compulsive symptom dimensions in 109 individuals with early psychosis (31 At-Risk Mental States [ARMS], 78 psychotic disorders with3 years of illness) and 59 healthy subjects. Obsessive-compulsive symptoms were assessed by the Obsessive-Compulsive Inventory - Revised. We also assessed the severity of psychotic symptoms, depressive symptoms and functioning. ARMS and psychotic disorder patients reported more obsessive-compulsive symptoms than did healthy subjects. The ARMS individuals also reported more overall and checking obsessive-compulsive symptoms compared with the PD patients. Different types of obsessive-compulsive symptoms were related with depressive symptoms in both diagnostic groups. However, a different pattern was observed in the relationship between obsessive-compulsive dimensions and functioning by diagnosis (better functioning in ARMS; poorer functioning in psychotic disorders). Our study suggests that obsessive-compulsive symptoms are present in the early stages of psychotic illness, as well as in individuals at risk for psychosis. Future prospective studies are needed to elucidate how obsessive-compulsive symptoms in ARMS may influence the prognosis in terms of global functioning and the risk of psychosis transition.

Background: Studies have associated maternal stress during pregnancy with CNS disorders including schizophrenia. In Danish register data we showed that the loss of a close relative during and after pregnancy was associated with offspring schizophrenia risk. It has been speculated that stressful life events enhance production of glucocorticoids that adversely affect neurodevelopment in the immature brain, increasing the risk of mental illness in adolescence or adult life. The authors hypothesized that the effect of bereavement was mediated via cortisol, and in part could be explained by variation in the gene HSD11B2 encoding the glucocorticoid regulating enzyme 11-β-hydroxysteroid-dehydrogenase type 2 (11βHSD2). Methods: A matched case-control study with 716 schizophrenia cases and 782 controls, matched on sex, exact date of birth, born in Denmark, alive and with no history of schizophrenia on the date of first diagnosis of schizophrenia of the matched case, and also including all their first-degree relatives. We used information from national registers and, to determine whether the effect of bereavement could be explained by variation in HSD11B2. Two single nucleotide polymorphisms (SNPs) from the locus of HSD11B2 were genotyped (rs5479 and 56303414), and one from a neighboring gene (rs9922624), and the data was analyzed with conditional logistic regression. Results: We found a significant protective effect of each of the variant alleles for rs9922624 (odds ratio (OR) 0.60, [95% confidence interval (CI), 0.42-0.88]) and rs5479 (OR 0.55 (95% CI 0.34-0.90). When stress at the age of 3-9 years co-occurred in individuals with the variant allele, we found that the risk of schizophrenia was increased, though not significant. The interaction between stress at the age of 3-9 years and the allele however was significant with (OR 3.02 (95% CI 1.32-6.93) and (OR 3.92 (95% CI 1.46-10.54) for rs9922624 and rs5479 respectively. Discussion: Our results suggest that functional variation in 11βHSD2 might be a predisposing factor for schizophrenia after stress exposure, since we found interaction between the SNPs in the gene and stress. However, maybe due to lack of power, we were not able to show any significant risk of having the allele after stress exposure in regard to schizophrenia.

Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with