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Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

Objective: This article describes the development and testing of the Functional Recovery tool (FR tool), a short instrument for assessing functional recovery during routine outcome monitoring of people living with serious mental illnesses. Methods: To assess functional recovery, mental health professionals conducted semistructured interviews with people living with serious mental illnesses on three areas of social functioning: daily living and self-care, work and study, and social contacts. Functioning in each of these areas over the past 6 months was rated on a 3-point scale: 0 (independent), 1 (partially independent), and 2 (dependent). The dichotomous overall outcome of the tool is defined as independent functioning in all areas. We analyzed interrater and test–retest reliability, sensitivity to change, and correlations with constructs that are assumed to be similar to the FR tool (quality of life in daily living, work, and social contacts) or divergent from it (symptomatic functioning). Results: The FR tool was administered to 840 individuals with serious mental illnesses in Dutch mental health care services, 523 of whom were followed up for 1 year (response rate 62%). The tool was easy to complete and was appropriate for policy evaluation and practice. However, when it was combined with more elaborate instruments, it added little extra clinical information. Interrater and test–retest reliability, convergent and discriminant validity, and sensitivity to change were rated sufficient to good. Conclusions and Implications for Practice: The FR tool could be a useful measure of functional recovery in addition to current measures of symptomatic remission and personal recovery in routine outcome monitoring. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Objective: Despite the increasing recognition in clinical practice of body image problems in other than appearance related mental disorders, the question remains how aspects of body image are affected in different disorders. The aim of this study was to measure body image in patients with a variety of mental disorders and to compare scores with those in the general population in order to obtain more insight in the relative disturbance of body image in the patients group compared to healthy controls. In a further exploration associations with self-reported mental health, quality of life and empowerment were established as well as the changes in body image in patients over time.Methods: 176 women and 91 men in regular psychiatric treatment completed the Dresden Body Image Questionnaire, the Outcome Questionnaire, the Manchester Short Assessment of Quality of Life and the Mental Health Confidence Scale. Measurements were repeated after four months.Results: Patients with mental disorders, especially those with post-traumatic stress disorder (PTSD), scored significantly lower on body image, with large effect sizes, in comparison with the healthy controls. Scores of patients from different diagnostic groups varied across domains of body image, with body acceptance lowest in the group with eating disorders, and sexual fulfillment extremely low in PTSD. Vitality did not differ significantly between the various disorders. Gender differences were large for body acceptance and sexual fulfillment and small for vitality. Associations of body image with self-reported mental health, quality of life and empowerment were moderate to strong. After four months of treatment positive changes in body image were observed.Conclusions: Negative body image is a common problem occurring in most patients with mental disorders. Diagnosis-specific profiles emerge, with PTSD being the most affected disorder. Body acceptance and sexual fulfillment were the most differentiating aspects of body image between diagnoses. Changes in body image occur over the course of treatment. (C) 2017 Elsevier Inc. All rights reserved.

The aim of this study was to develop and validate the Adult Social Behavior Questionnaire (ASBQ), a multidimensional Autism Spectrum Disorder (ASD) questionnaire that contains both a self report version and a version to be completed by someone close. Psychometric qualities, convergence between self report and other report ratings, and scores in a group diagnosed with ASD and multiple comparison groups were examined.Principal Component Analyses yielded a structure with six dimensions (reduced contact, reduced empathy, reduced interpersonal insight, violation of social conventions, insistence on sameness, and sensory stimulation/motor stereotypies) for both self- and other-report versions. Reliability estimates and correlations between self- and other-ratings were good and the score profile on the 44-item ASBQ differentiated a group with ASD from a non clinical group and patients with depression, schizophrenia and ADHD.We conclude that the ASBQ is a short and easy to apply questionnaire that captures the heterogeneous nature of ASD. It yields a score profile among six ASD problem domains both from the perspective of the patient and from a significant other. (C) 2016 Elsevier Ltd. All rights reserved.

BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim of this study was twofold: (1) to investigate whether childhood urbanicity moderates the effect of childhood trauma, in a model predicting psychotic disorder; (2) to investigate whether there is an association between the urban environment and childhood trauma and whether this is moderated by genetic liability for psychotic disorder. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 1119) and 589 healthy controls from the Netherlands and Belgium were studied. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire Short Form. Urban exposure was defined at four levels, considering the population density, using data from Statistics Netherlands and the equivalent database in Belgium. RESULTS: There was a significant interaction between childhood urbanicity on the one hand and childhood trauma on the other, indicating that trauma was significantly associated with psychotic disorder, with increasing odds ratios for higher levels of childhood urbanicity. In addition, there was weak evidence that childhood urbanicity was associated with childhood trauma in the patient group: higher levels of childhood urbanicity were associated with higher trauma scores. CONCLUSION: The urban environment may moderate the risk-increasing effect of childhood trauma for psychotic disorder and childhood urbanicity may be a risk factor for childhood trauma in individuals who later develop psychotic disorder.

Finding clusters in a complex dataset is not straightforward. Different indices were developed to quantify the number of clusters. Their performances were studied using unrealistic simulations, since they were considered at low dimensions. We investigated 14 indices for eight-dimensional data using simulations based on cognition measures. We focused on hierarchical clustering with Ward’s agglomerative technique. Results indicated that Duda and Hart, Hartigan and Gap/pc were best performing. They estimated the number of clusters within ±1 with high probabilities. Duda and Hart index was most consistent, while Gap/pc and WGap/pc together made a good distinction between single and multiple clusters.

Objective: Impaired Theory of Mind (ToM) and insecure (adult) attachment styles have been found in persons with schizophrenia as well as in their healthy siblings. ToM refers to the ability to infer mental states of self and others including beliefs and emotions. Insecure attachment is proposed to underlie impaired ToM, and comprises avoidant (discomfort with close relationships, high value of autonomy) and anxious (separation anxiety, dependency on others) attachment. Insight into the association between attachment style and ToM is clinically relevant, as it enhances our understanding and clinical approach to social dysfunction in schizophrenia. Therefore, we studied the association between insecure attachment styles and ToM in patients with schizophrenia, their siblings, and healthy controls. Methods: A total of 111 patients with a diagnosis in the schizophrenia spectrum, 106 non-affected siblings and 63 controls completed the Psychosis Attachment Measure, the Conflicting Beliefs and Emotions, a subsection of the Wechsler Adult Intelligence Scale, and the Childhood Trauma Questionnaire-Short Form. Severity of symptoms was assessed with the Community Assessment of Psychic Experiences and the Positive and Negative Syndrome Scale. Results: After controlling for sex, intelligence, history of trauma and symptom severity, avoidant attachment was significantly associated with cognitive as well as with affective ToM, showing U-shaped associations, indicating better ToM performance for patients with lower or higher levels of avoidant attachment compared to medium levels. Anxious attachment in patients was associated with more problems in cognitive ToM. Conclusion: The results from this study support the idea that an anxious attachment style is associated with worse ToM performance in patients. Results also suggested a potential protective role of higher levels of avoidant attachment on ToM. These findings bear clinical relevance, as activation of (insecure) attachment mechanisms may affect interpersonal relations, as well as therapeutic working alliance. Further clarification is needed, especially on associations between ToM and avoidant attachment.

BACKGROUND: Body image has implications for psychosocial functioning and quality of life and its disturbance is reported in a broad range of psychiatric disorders. In view of the lack of instruments in Dutch measuring body image as a broad concept, we set out to make an instrument available that reflects the multidimensional character of this construct by including more dimensions than physical appearance. The Dresden Körperbildfragebogen (DBIQ, Dresden Body Image Questionnaire) particularly served this purpose. The DBIQ consists of 35 items and five subscales: body acceptance, sexual fulfillment, physical contact, vitality, and self-aggrandizement. The main objective of the present study was to evaluate the psychometric properties of the Dutch translation of the Dresden Body Image Questionnaire (DBIQ-NL) in a non-clinical sample.METHODS: The psychometric properties of the DBIQ-NL were examined in a non-clinical sample of 988 respondents aged between 18 and 65. We investigated the subscales' internal consistency and test-retest reliability. In order to establish construct validity we evaluated the association with a related construct, body cathexis, and with indices of self-esteem and psychological wellbeing. The factor structure of the DBIQ-NL was examined via confirmatory factor analysis (CFA). The equivalence of the measurement model across sex and age was evaluated by multiplegroup confirmatory factor analyses.RESULTS: Confirmatory factor analyses showed a structure in accordance with the original scale, where model fit was improved significantly by moving one item to another subscale. Multiple group confirmatory factor analysis across sex and age demonstrated partial strong invariance. Internal consistency was good with little overlap between the subscales. Temporal reliability and construct validity were satisfactory.CONCLUSION: Results indicate that the DBIQ-NL is a reliable and valid instrument for non-clinical subjects. This provides a sound basis for further investigation of the DBIQ-NL in a clinical sample.

Background: Auditory hallucinations are experienced by 60-80% of all patients diagnosed with a schizophrenia spectrum disorder. However, in this patient group, the prevalence of hallucinations in multiple sensory modalities, i.e. multimodal hallucinations (MMHs), is unknown.Aims: To assess the prevalence of MMHs in patients diagnosed with a schizophrenia spectrum disorder, data were analyzed from 750 patients who participated in the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study.Method: We drew on the section of the CASH (Comprehensive Assessment of Symptoms and History) that probes into the lifetime presence of auditory, visual, somatic/tactile, and olfactory hallucinations.Results: A lifetime prevalence of 80% was found in this group for hallucinations in any of these modalities. Within the whole group, 27% of the participants reported unimodal hallucinations and 53% MMHs. There were no significant differences in prevalence rate for Dutch versus migrant participants from Morocco, Turkey, Surinam or the (former) Dutch Antilles.Conclusion: We conclude that MMHs, rather than auditory hallucinations, are the most frequent perceptual symptom of patients diagnosed with a schizophrenia spectrum disorder. Our data also suggest that hallucinations experienced in a single sensory modality (notably auditory ones) stochastically increase the risk for more sensory modalities to join in. We recommend that future studies take into account all 14 sensory modalities in which hallucinations can be experienced. For this we provide a classification of MMHs that allows characterization of their serial versus simultaneous occurrence and their congruent versus incongruent nature. (C) 2016 The Authors. Published by Elsevier B.V.

Cannabis use has been associated with favorable outcomes on metabolic risk factors. The cause of this relation is still unknown. In this study we investigated whether this effect is mediated by the AKT1 gene, as activation of the related enzyme by cannabis may cause metabolic changes.Six Single Nucleotide Polymorphisms (SNPs) of the AKT1 gene (rs1130214, rs1130233, rs2494732, rs2498784, rs3730358, and rs3803300) of patients with psychotic disorders (n = 623) were related to Body Mass Index (BMI), levels of glycosylated hemoglobin (HBA(1c)) and total metabolic risk. Next, mediation analysis was performed with BMI as outcome, cannabis as predictor, and AKT1 as mediator. Cannabis use was inversely related to BMI but not with levels of HBA(1c) and totalmetabolic risk. Moreover, out of 6 AKT1 SNPs, rs2494732 was associated with cannabis use, but AKT1 did not mediate the effect of cannabis on BMI.In conclusion, cannabis use is likely to be associated with a lower BMI in patients with a psychotic disorder. Moreover, AKT1 risk alleles may increase the incidence of cannabis use in patients with a psychotic disorder, but AKT1 does not appear to mediate the effect of cannabis on BMI. (C) 2016 Elsevier B.V. All rights reserved.

Background: Schizophrenia is characterized by positive and negative symptoms, but recently anomalous self-experiences, e.g. exaggerated self-consciousness (hyperreflectivity), receive more attention as an important symptom domain in schizophrenia patients. The semi-structured interview, the Examination of Anomalous Self-Experience (EASE) [Psychopathology 2005;38:236-258], examines experiences of a disturbed sense of self in a sophisticated but time-consuming manner. Therefore, we proposed the Self-Experience Lifetime Frequency scale (SELF), an instrument intended to screen for self-disturbance phenomena. Here we compared scores of patients, their siblings and healthy controls on the SELF. Methods and Sampling: The SELF is composed of a validated screener for symptoms of depersonalization complemented by questions covering several other domains of self-disturbance. A total of 426 patients with a psychotic disorder, 526 of their unaffected siblings, and 297 healthy controls completed the SELF. Patients' scores on the 12 items of the SELF were subjected to an explorative principal axis factor analysis (PAF); composite scores on factor components were compared between the three participant groups. Results: The PAF revealed two components, explaining 43.9 and 9.5% of variance, respectively. The first component represents a disturbance of self-awareness; the second component reflects (milder forms of) diminished self-affection or depersonalization. The two components of the SELF revealed good internal consistency (component 1, α = 0.88; component 2, α = 0.79; ρ = 0.85). Patients showed significantly higher scores on both factor components in comparison with both siblings and controls. No significant differences were found between siblings and controls. Conclusions: The findings of the current study suggest that the SELF comprises two components of self-disturbance. Patients reported more (severe) symptoms of self-disturbance on both components, suggesting that it is feasible to screen for self-disturbance phenomena in patients with psychotic disorders with the SELF. Screening for symptoms of self-disturbance is important since these symptoms are associated with suffering and, moreover, these phenomena may mark the transition from intact to aberrant reality testing.

The proneness-persistence-impairment (PPI) model states that psychotic experiences are more likely to lead to impairment if their expression becomes persistent. Higher genetic risk for psychosis is known to affect proneness and persistence of subclinical positive symptoms. Less is known about potential effects of genetic risk on the course of subclinical negative symptoms, impairment, and their subsequent associations. The current study examined these issues in a large sample (n=1131), consisting of individuals with higher genetic risk (siblings of patients with psychotic disorders, n=703) and lower genetic risk (controls without a family member with lifetime psychosis, n=428). Psychotic experiences were assessed with the CAPE questionnaire, at two time points three years apart. Participants were allocated to one of four groups representing developmental course: stable low, decreasing, increasing or persisting subclinical positive/negative symptoms. Lifetime clinical psychosis was an exclusion criterion at baseline. Higher genetic risk status was found to be associated with a persisting course of both subclinical positive and negative symptoms, symptom-related distress and functional impairment. There is no evidence for an effect of genetic risk status on the association between developmental course and impairment. The results of the current study underline the importance of assessing psychotic experiences in the context of genetic risk, multidimensional and over time. Additionally, the current findings both underscore and contribute to the PPI model: psychotic experiences are more likely to lead to impairment if their expression becomes persistent, both in individuals with higher and lower genetic risk for psychosis. publisher: Elsevier articletitle: Developmental course of subclinical positive and negative psychotic symptoms and their associations with genetic risk status and impairment journaltitle: Schizophrenia Research articlelink: http://dx.doi.org/10.1016/j.schres.2016.03.028 content_type: article copyright: © 2016 Published by Elsevier B.V. ispartof: Schizophrenia Research vol:174 issue:1 pages:177-182 ispartof: location:Netherlands status: published

Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (−0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (−0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. Refereed/Peer-reviewed

Background In outpatient forensic psychiatry, assessment of re-offending risk and treatment needs by case managers may be hampered by an incomplete view of client functioning. The client’s appreciation of his own problem behaviour is not systematically used for these purposes. The current study tests whether using a new client self-appraisal risk assessment instrument, based on the Short Term Assessment of Risk and Treatability (START), improves the assessment of re-offending risk and can support shared decision making in care planning. Methods In a sample of 201 outpatient forensic psychiatric clients, feasibility of client risk assessment, concordance with clinician assessment, and predictive validity of both assessments for violent or criminal behaviour were studied. Results Almost all clients (98 %) were able to fill in the instrument. Agreement between client and case manager on the key risk and protective factors of the client was poor (mean kappa for selection as key factor was 0.15 and 0.09, respectively, and mean correlation on scoring −0.18 and 0.20). The optimal prediction model for violent or criminal behaviour consisted of the case manager’s structured professional risk estimate for violence in combination with the client’s self-appraisal on key risk and protective factors (AUC = 0.70; 95%CI: 0.60–0.80). Conclusions In outpatient forensic psychiatry, self-assessment of risk by the client is feasible and improves the prediction of re-offending. Clients and their case managers differ in their appraisal of key risk and protective factors. These differences should be addressed in shared care planning. The new Client Self-Appraisal based on START (CSA) risk assessment instrument can be a useful tool to facilitate such shared care planning in forensic psychiatry. Electronic supplementary material The online version of this article (doi:10.1186/s12888-015-0500-3) contains supplementary material, which is available to authorized users.

Long-term recovery rates in schizophrenia after early antipsychotic dose reduction Objective Comparing 7-year outcome of early antipsychotic dose-reduction/discontinuation (DR) with maintenance treatment (MT) on remission, relapse and recovery in remitted first episode psychosis (FEP). Method FEP patients (N=128) symptomatically remitted for 6m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables. Results 103 patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 ( P =.014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20mg in DR vs. 3.60mg in MT ( P =.031). Relapse-rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years. Conclusion DR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapse-rates in GD were higher, these equaled those in MT from 3 years to the end of the study.

Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D-2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their anti psychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients' relatively low dose range, altered emotional experiences did not appear to relate to the level of D-2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033-2.015]); possibly due to higher D-2 receptor occupancies as estimated by dose equivalents. (C) 2016 Published by Elsevier Ireland Ltd.

A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and alpha(1)-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce.

High rates of obsessive-compulsive symptoms (OCS) in schizophrenia require pathogenic explanations. Personality traits may represent risk and resiliency factors for the development of mental disorders and their comorbidities. The aim of the present study was to explore the associations between Five-Factor Model (FFM) personality traits and the liability for OCS in patients with psychotic disorders and in their un-affected siblings. FFM traits, occurrence and severity of OCS and (subclinical) psychotic symptoms were assessed in 208 patients and in 281 siblings. Differences in FFM traits between participants with vs. without comorbid OCS were examined and the predictive value of FFM traits on group categorization was evaluated. Associations between FFM traits and OCS severity were investigated. Patients and siblings with OCS showed significantly higher Neuroticism compared to their counterparts without OCS. Neuroticism was positively associated with higher OCS severity and significantly predicted group assignment in both patients and in siblings. Patients with comorbid OCS presented with lower scores on Extraversion and Conscientiousness. Higher Neuroticism, and to a lesser degree lower Extraversion and Conscientiousness might add to the vulnerability of patients with a psychotic disorder to also develop OCS. Future prospective studies are needed to elucidate proposed personality-psychopathology interrelations and possible mediating factors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Cross-Disorder Working Group of the Psychiatric Genomics Consortium - Vicente A.M. Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25640677/ Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk

BackgroundThe association between childhood trauma and psychotic and depressive symptomatology is well established. However, less is known about the specificity and course of these symptoms in relation to childhood trauma.MethodIn a large sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n = 1057) and controls (n = 589), multivariate (mixed-effects) regression analyses with multiple outcomes were performed to examine the association between childhood trauma and psychotic and depressive symptomatology over a 3-year period.ResultsA dose–response relationship was found between childhood trauma and psychosis. Abuse was more strongly associated with positive symptoms than with negative symptoms whereas the strength of the associations between neglect and positive and negative symptoms was comparable. In patients, similar associations between childhood trauma and psychotic or depressive symptoms were found, and in siblings and controls, stronger associations were found between trauma and depressive symptomatology. Childhood trauma was not related to a differential course of symptoms over a 3-year time period.ConclusionsIn congruence with earlier work, our findings suggest that childhood trauma, and abuse in particular, is associated with (subthreshold) psychosis. However, childhood trauma does not seem to be associated with a differential course of symptoms, nor does it uniquely heighten the chance of developing (subthreshold) psychotic symptomatology. Our results indicate that trauma may instead contribute to a shared vulnerability for psychotic and depressive symptoms.

Background Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies.Methods We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (Results We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings.Limitations The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites.Conclusion These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

BackgroundLong-term functional outcome of dose-reduction/discontinuation strategies in first-episode psychosis (FEP) has not been studied before. The present study compared 7-year outcome of an early antipsychotic dose-reduction/discontinuation (DR) strategy with maintenance treatment (MT). Primary outcome was (symptomatic and functional) recovery; relapse rates, functional and symptomatic remission were secondary outcomes.MethodsFEP patients (n = 128) symptomatically remitted for 6 m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables.ResultsOne hundred and three patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 (P = .014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20 mg in DR vs. 3.60 mg in MT (P = .031).Relapse rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years.ConclusionDR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapse rates in GD were higher, these equalled those in MT from 3 years to the end of the study. While the necessity of immediate antipsychotic treatment in FEP and positive symptoms relapse is robustly demonstrated in a great number of studies, this study suggests that we are faced with a dilemma concerning the drawbacks of long-term maintenance antipsychotic treatment on functional capacity. Though antipsychotic discontinuation appears only feasible without relapse in a substantial minority of patients, guided dose-reduction as far as positive symptoms remain subsided and allow it, appears a feasible strategy in view of functional recovery, doing justice to both sides of the dilemma.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Background: Substantial evidence exists about emotion processing (EP) impairments in schizophrenia patients. However, whether these deficits are present primarily during psychosis (i.e., state dependent) or an integral part of the disorder (i.e., trait dependent) remains unclear.Methods: EP was assessed with the degraded facial affect recognition task in schizophrenia patients (N = 521) and healthy controls (N = 312) at baseline (T1) and after a three year follow-up (T2). In schizophrenia patients symptomatic remission was assessed with the Positive and Negative Syndrome Scale (PANSS) remission tool. Patients were divided into four groups: remission T1 and remission T2 (RR); remission T1 and non-remission T2 (RN); non-remission T1 and non-remission T2 (NN) and non-remission T1 and remission T2 (NR). Factorial repeated measures ANCOVA was used to compare EP performance over time between groups. Age, gender and general cognition were included as covariates.Results: Schizophrenia patients performed worse than healthy controls on EP at T1 (p = 0.001). The patients that were in symptomatic remission at both time points (the RR group) performed worse than the healthy controls at T2 (p Conclusion: The results show relatively poor EP performance in schizophrenia patients compared to healthy controls. EP performance in schizophrenia patients was associated with symptomatic remission. The results provide support for the hypothesis that EP deficits in schizophrenia are both state and trait dependent. (C) 2014 Elsevier B.V. All rights reserved.