Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants with Treatment Resistance in Schizophrenia

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10501) and individuals with non-TRS (n = 20325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85490 participants (48635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P =.001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P =.04). Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance

Social Phobia, intraversion/Extraversion and School Achievement in Adolescents

Current data indicate that the onset of social phobia starts from adolescence. The main purpose of this study is to investigate if the level of social phobia changes as a function of internal-external personality types, level of school achievement and sociodemographic factors, in a group of adolescents

Determination of difference between groups in multivariate analysis of variance: An application

WOS: 000254583000005Objective: Although there is a healthy trend toward employment of multivariate analysis of variance (MANOVA) in the analysis of data from experiments which involve multiple dependent variables, there remains a need to demonstrate the wide variety of data analytic techniques available for post hoc analysis of statistically significant multivariate results. As a post-hoc test, using Stepdown Analysis after MANOVA was explained with application in this study, Material and Methods: In this study, the data set were used that contain 19 healthy (control group) pregnant, 21 pre-eclamptic pregnant and I I eclamptic pregnant, who submitted to Obstetric and Gynecologist Department of Research Hospital of Y.Y. University Medical School between 2004-2005 years. Urinary protein, systolic blood pressure, lactate dehydrogenase, alanine amino transferase, aspartat transaminase, malonyl dialdehyde and. platelets measurements were measured from pregnants. Results: It showed that urinary protein, systolic blood pressure and LDH were affected on groups' differences according to results of Stepdown analysis. Conclusion: Stepdown analysis, a test for the incremental discriminatory power of a dependent variable after the effects of other dependent variables has been taken into account. This analysis is similar to stepwise regression or discriminant analysis in that it relies on a specific order of entry to determine how much an additional dependent variable adds to the explanation of the differences between the groups in the MANOVA analysis. Because of this properties, Stepdown analysis is a suitable post-hoc tes for MANOVA

Clinical variables associated with suicide attempts in schizophrenia before and after the first episode

The aim of this study was to investigate variables associated with suicide attempts in schizophrenia before and after the first episode. We evaluated history of past sucide attempts, clinical symptoms, level of functioning and cognitive performances of 172 patients with first-episode schizophrenia at first admission. Information was collected regarding clinical symptom severity, treatment compliance, and suicide attempts during the follow-up. We found that 16.5% of the patients attempted suicide before admission, and 6.2% of them attempted suicide during the follow-up. The patients who had attempted suicide before admission were mostly women, and more likely to be hospitalized in first year of follow up. BPRS-depression subscale score at admission and alcohol/substance use appeared as independent variables that found associated with suicide attempts prior to admission in logistic regression analysis. The patients who attempted suicide during the follow-up had significantly higher BPRS-depression subcale scores at sixth months of follow-up. Treatment compliance during the first 6 months and duration of remission was lower in this group. Our findings suggest that longer duration of first hospital treatment, the presence of depressive symptoms, and nonadherence to treatment in early phases of follow up after FES are predictors of suicide attempts. On the other hand, keeping remission during the follow-up protects against suicide attempts. (C) 2015 Elsevier Ireland Ltd. All rights reserved

The value of power Doppler ultrasonography in the differential diagnosis of intracranial extraaxial fluid collections

PURPOS

Menstrual Cycle-Related Changes in Women with Schizophrenia: A Resting-State fMRI Study

Introduction: Different influences of ovarian hormones in schizophrenia (SCZ) have been reported, but no study to date has assessed their effects on the brain dynamics at rest. The present study aimed to examine the hormonal and clinical changes related to the menstrual cycle and alterations in the resting-state functional connectivity (RS-FC) depending on cycle phase and/or hormonal fluctuations in SCZ. Method: This study was conducted based on both between- and within-subject experimental designs, including 13 clinically stable female patients with SCZ (32 +/- 7.7 years) and 13 healthy women (30 +/- 7.3 years). RS-functional magnetic resonance imaging (fMRI) scanning, as well as hormonal and clinical assessments, was applied to each participant twice during two cycle phases: early follicular and mid-luteal. Results: A difference in mid-luteal progesterone levels was found between groups, with a large effect size (Cohen's d) of 0.8 (p < 0.05). Also, the estradiol levels negatively correlated with the negative symptom severity of the patients during their mid-luteal phase. In the patients, estrogen positively correlated with the auditory network connectivity in the left amygdala during the early follicular phase. In the controls, progesterone had positive correlations with the connectivity of the posterior default mode and the left frontoparietal networks in the bilateral precuneus during the early follicular phase and had a negative correlation with the executive control network connectivity in the mid-luteal phase. Conclusion: The present study showed hormonal differences between groups and suggested that the levels of cycle-dependent hormones might be associated with the changes in clinical symptom severity and the RS-FC in the groups. Our RS-fMRI findings warrant further investigation

Relationship of obsessive-compulsive symptoms to clinical variables and cognitive functions in individuals at ultra high risk for psychosis

Few studies have investigated the relationship between obsessive-compulsive symptoms (OCS) and clinical variables, and cognition in individuals at ultra high-risk (UHR) for psychosis. The aim of this study was to evaluate the frequency of OCS and their relationship with clinical variables and cognitive functions in individuals at UHR. Eighty-four individuals at UHR for psychosis were administered the Brief Psychiatric Rating Scale, the Yale-Brown Obsession Compulsion Symptom Check List and, the Calgary Depression Scale for Schizophrenia. A cognitive test battery was also applied. We compared the clinical, functional, and cognitive parameters of individuals at UHR with and without OCS and healthy controls. Thirty-five percent of the UHR sample had at least two obsessions/compulsions. The duration of subthreshold psychotic symptoms was longer in individuals with OCS. Those who can work/study before first presentation were more frequent in OCS-positive group. CDSS scores were higher in those with OCS. Compared to controls, OCS-negative group's performance was worse in 8 cognitive test items, while OCS-positive group performed worse in only one cognitive test item. Our findings suggest that OCS are common in the UHR group. OCS might be related to higher level of depression, but better work/study performance, and less cognitive deficits in UHR group

Effects of Gender Reassignment on Quality of Life and Mental Health in People with Gender Dysphoria

Objective: Our purpose was to compare the life style, family and social relationships (social adaptation) and the quality of life in people with gender dysphoria with and without history of sex reassignment surgery