Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

Discrimination in the workplace, reported by people with major depressive disorder: a cross-sectional study in 35 countries.

OBJECTIVE: Whereas employment has been shown to be beneficial for people with Major Depressive Disorder (MDD) across different cultures, employers' attitudes have been shown to be negative towards workers with MDD. This may form an important barrier to work participation. Today, little is known about how stigma and discrimination affect work participation of workers with MDD, especially from their own perspective. We aimed to assess, in a working age population including respondents with MDD from 35 countries: (1) if people with MDD anticipate and experience discrimination when trying to find or keep paid employment; (2) if participants in high, middle and lower developed countries differ in these respects; and (3) if discrimination experiences are related to actual employment status (ie, having a paid job or not). METHOD: Participants in this cross-sectional study (N=834) had a diagnosis of MDD in the previous 12 months. They were interviewed using the Discrimination and Stigma Scale (DISC-12). Analysis of variance and generalised linear mixed models were used to analyse the data. RESULTS: Overall, 62.5% had anticipated and/or experienced discrimination in the work setting. In very high developed countries, almost 60% of respondents had stopped themselves from applying for work, education or training because of anticipated discrimination. Having experienced workplace discrimination was independently related to unemployment. CONCLUSIONS: Across different countries and cultures, people with MDD very frequently reported discrimination in the work setting. Effective interventions are needed to enhance work participation in people with MDD, focusing simultaneously on decreasing stigma in the work environment and on decreasing self-discrimination by empowering workers with MDD.

Negative symptom subgroups have different effects on the clinical course of schizophrenia after the first episode: a 24-month follow up study.

OBJECTIVE: The aim of this study was to assess the factor structure of negative symptoms in first-episode schizophrenia (FES), and to examine the relationship of these factors with clinical course and functioning of patients during the two-year follow up. METHOD: We assessed 174 drug-naïve patients with FES using Brief Psychiatric Rating Scale-Expanded (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Global Assessment of Functioning (GAF) and a cognitive battery at admission. The scales were repeated monthly during follow up. We recorded the patients' functioning levels, remission, and work status after 12 and 24 months. RESULTS: A two-factor structure was found at the baseline, whereas one factor was found after 12 and 24 months. Expressive deficit (ED) factor consisted of alogia and blunted affect, and motivation-pleasure deficit (MPD) factor consisted of avolition and anhedonia. ED factor was related to earlier onset and remission, and it was negatively correlated with duration of education and cognitive test scores. MPD factor was related to duration of untreated psychosis, family history of schizophrenia, and work status, and it appeared as the only independent variable that contributed to the baseline GAF score in linear regression analysis. CONCLUSION: Our findings suggest that the factors have different aetiologies and impacts on the clinical course of schizophrenia and functioning after FES.

Anticipated discrimination among people with schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the level of anticipated discrimination in people with schizophrenia (n = 732) from 27 countries in the International Study of Discrimination and Stigma Outcomes (INDIGO). METHOD: Anticipated discrimination was assessed through four questions of Discrimination and Stigma Scale. Twenty-five individuals were identified at each site who were reasonably representative of all such treated cases within the local area. RESULTS: Sixty-four per cent of the participants reported that they had stopped themselves from applying for work, training or education because of anticipated discrimination. Seventy-two per cent of them reported that they felt the need to conceal their diagnosis. Expecting to be avoided by others who know about their diagnosis was highly associated with decisions to conceal their diagnosis. Those who concealed their diagnosis were younger and more educated. The participants who perceived discrimination by others were more likely to stop themselves from looking for a close relationship. Anticipated discrimination in finding and keeping work was more common in the absence than in the presence of experienced discrimination, and the similar findings applied to intimate relationships. CONCLUSION: This study shows that anticipated discrimination among people with schizophrenia is common, but is not necessarily associated with experienced discrimination.

No gender differences in social outcome in patients suffering from schizophrenia.

Differences between female and male patients with schizophrenia in psychopathology and course of illness have frequently been reported. However, the influence of sex on symptomatic and social remission is still an open issue. In the present study, differences between males and females in both clinical and social remission rates and in scores on several scales assessing social functioning were evaluated in 295 stabilized patients with schizophrenia, schizoaffective or delusional disorder. Female patients, as compared with males, showed a later onset of the illness, less negative symptoms and less frequent alcohol abuse. No significant difference was found between females and males in the rate of symptomatic and functional remission. No significant effect of sex was observed on any index of social functioning.

Employment and its relationship with functionality and quality of life in patients with schizophrenia: EGOFORS Study.

UNLABELLED: The aim of this study is to investigate the relationship between work/study status and symptom severity, functionality and quality of life (QoL) in schizophrenia patients. METHODS: Two-hundred and ninety-five chronic schizophrenia patients from 11 centres were included in the study. Symptom severity was measured with Positive and Negative Syndrome Scale for schizophrenia. QoL and functionality was assessed with Global Assessment of Functioning Scale, Quality of Life Scale, Personal and Social Performance Scale, Psychosocial Remission in Schizophrenia Scale, Functional Recovery Scale in Schizophrenia, Performance-Based Skills Assessment-Brief Version and Subjective Well-being under Neuroleptics Scales. RESULTS: Two-third of the participants (n=194) were unemployed. Forty (13.6%) of the participants were involved in full-time work/study, 29 (9.8%) people were involved in part-time work/study, 13 (4.4%) people were engaged in work/study below 50% of the time, but their job was classified as regular and independent. Those who work/study had lower symptoms, better functioning and higher levels of QoL. Also those who work/study full-time displayed better results on these measures than the participants involved in part-time work/study. Age, education, severity of negative symptoms, gender and duration of remission were found to be related to employment status in the logistic regression analysis. CONCLUSIONS: Our findings suggest that work/study status is an important component of functionality.

COMT Val 158 Met polymorphism is related with interpersonal problem solving in schizophrenia.

OBJECTIVE: The aim of this study was to investigate associations between COMT Val(158)Met polymorphism, and interpersonal problem solving capacity and cognitive functions in schizophrenia. METHODS: COMT Val(158)Met polymorphism was studied with ARMS-PCR method in 99 outpatients with schizophrenia. Brief Psychiatric Rating Scale was used to assess symptom severity. The Assessment of Interpersonal Problem Solving Skills (AIPSS) was used to evaluate problem solving capacity. Continuous Performance Test (CPT) and Wisconsin Card Sorting Test (WCST), were used to measure cognition. RESULTS: Patients with Met/Met genotype had higher AIPSS subscores for detecting the problem, than those with Val/Val at baseline (p=0.02). Met allele was also found to be related with higher AIPSS-receiving skills (p=0.04). Val allele was found to be related with more commission errors in CPT (p=0.03). There was no relation between Val(158)Met polymorphism and WCST and clinical measurements. CONCLUSION: Our findings suggest that Val allele might be related to poor performance on detecting the interpersonal problems, and attention in schizophrenia.

The effects of childhood trauma in patients with first-episode schizophrenia.

OBJECTIVE: To evaluate the impact of childhood trauma on psychopathology in 57 patients with first-episode schizophrenia. METHOD: Psychopathology was assessed by Brief Psychiatric Research Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) at first admission. Childhood trauma was assessed by Childhood Abuse Questionnaire and Childhood Trauma Questionnaire (CTQ) after discharge. RESULTS: Frequencies of childhood sexual abuse (CSA), emotional abuse (CEA) and physical abuse (CPA) were reported by 29.8%, 40.9% and 13.6% of the patients respectively. Histories of childhood emotional neglect (CEN) and physical neglect were found in 29.5% and 20.5% of the patients respectively. The patients reporting CSA had higher SAPS scores at admission, and had more suicide attempts before admission. The patients with history of CEA had more hallucinations and delusions of mind reading at admission. CPA, CEA and mean scores of CTQ correlated with the number of siblings. CONCLUSION: Our findings suggest that childhood trauma may alter the presentation of schizophrenia in first admission.

Quantitative proton MR spectroscopy findings in the corpus callosum of patients with schizophrenia suggest callosal disconnection.

BACKGROUND AND PURPOSE: The callosal disconnectivity theory was previously proposed to explain the pathophysiology of schizophrenia. The goal of this study was to investigate the metabolic integrity of the corpus callosum in patients with schizophrenia by proton MR spectroscopy. MATERIALS AND METHODS: Twelve first-episode and 16 chronic patients meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for schizophrenia and 28 age- and sex-matched control subjects were enrolled in the study. We measured the absolute concentrations of neurometabolites and T2 relaxation times of tissue water (T2B) in the genu of the corpus callosum by using the internal water-reference method. The severity of symptoms in patients was rated by means of psychopathology scales. Differences in neurometabolite concentrations and T2B values between the patients and control subjects were assessed. We also investigated the correlation of metabolite concentrations with the severity of symptoms. RESULTS: N-acetylaspartate (NAA) concentrations were significantly lower in the first-episode as well as in chronic patients, compared with respective control subjects (P < .001). NAA concentrations in the first-episode and chronic patient groups were negatively correlated with both the Brief Psychiatry Rating Scale and the Scale for Assessment of Negative Symptoms scores (P < .001). There was a significant negative correlation between the NAA concentrations and the Scale for Assessment of Positive Symptoms scores in all patients (P = .028). T2B values were significantly higher in the patients, compared with the control subjects (P < .001). CONCLUSION: Decreased NAA concentration in the corpus callosum correlates with psychopathology in schizophrenia. This finding, together with prolonged T2B values of the corpus callosum, supports the previously proposed callosal disconnection theory concerning the pathophysiology of schizophrenia.

[Frequency of obsessive compulsive symptoms and disorder in patients with schizophrenia: importence for prognosis]. / Fréquence des symptômes et du trouble obsessionnel compulsif chez les personnes atteintes de schizophrénie et leur importance pour le pronostic.

OBJECTIVE: The objective is to study the comorbidity rate of obsessive compulsive disorder and obsessive compulsive symptoms in patients with schizophrenia and their relation with the course of this illness. DESIGN: 73 out-patients from Istanbul Medical Faculty Department of Psychiatry and 4th Unit of Bakirköy Mental Hospital who met the DSM III-R criteria for schizophrenia were recruited for this study. Other inclusion criteria were being out of acute exacerbation phase of schizophrenia. Yale-Brown Obsessive-Compulsive Scale, Yale Brown Obsessive Compulsive Symptom Screening Inventory were applied to patients. RESULTS: Comorbidity rate of obsessive-compulsive disorder in patients with schizophrenia was 9.6%, and also obsessive compulsive symptoms were detected 31% of patients. Aggressive obsessions were seen most frequently. These symptoms were also reported more frequently in the patients whose Global Assessment of Functionality score was higher than 45 points. Suicide attempts in psychiatric history were significantly higher for patients with obsessive-compulsive symptoms. CONCLUSION: Our findings indicate that obsessive-compulsive symptoms are seen more frequently than previously reported, and have no major effect upon the course of schizophrenia.

The evaluation of anxiety and salivary cortisol levels in patients with oral lichen planus.

OBJECTIVE: The aim of this study was to determine any association between anxiety and salivary cortisol levels in oral lichen planus (OLP) patients by the case-control method. DESIGN RELEVANT: Forty patients with OLP were evaluated. The OLP diagnosis was established through a composite of accepted clinical and histopathological characteristics. Forty patients from the register of patients who obtained general dental care were selected as controls. MATERIAL AND METHOD: The saliva samples collected between 9:00 and 9:15 am were analysed for the level of cortisol with Cortisol EIA that used competitive enzyme-linked immunosorbent assay method. Trait and state anxiety levels of 80 patients were measured using the Spielberger's State-Trait Anxiety Inventory. RESULTS: The mean level of cortisol from 40 saliva samples in study group was 1.46 and 0.93 microg dl(-1) in 40 controls (P=0.001). The mean level for state anxiety in the study group were 48.85 and 39.45 in control group (P=0.001). Trait anxiety levels in study group were 49.77 and 38.51 in control group (P=0.001). We found that salivary cortisol, state and trait anxiety levels in OLP group were significantly higher than in the control group. CONCLUSION: Because of the fact that the level of anxiety and salivary cortisol of OLP patients were high, our findings concluded that this disease is closely related with stress. Thus besides traditional treatment of OLP patients, our findings suggest that psychological support is also needed.

Predictors of lithium prophylaxis in bipolar patients.

BACKGROUND: This study aimed to investigate the demographical and clinical factors and their predictive powers before and at the end of the 6th and 12th month of lithium prophylaxis. METHODS: Subjects meeting the following criteria were included in the investigation: (1) bipolar patients (DSM-IV); (2) having at least a 3-year lithium prophylaxis; (3) being in either the 'definite poor' or 'definite good' response groups. Both groups were compared regarding sociodemographic and clinical variables. RESULTS: At the pretreatment point of the prophylaxis, four variables that could predict poor response with 74.1% power were severe episodes, higher ratio of mania/depression, psychotic index episode and being unmarried. At the end of the 6th month, the five variables having 84.89% predictive power for poor response were again the previous three variables and additionally bipolar I diagnosis and poor response to the first 6 months of lithium. At the end of the 12th month, the three variables for poor response had 91.37% predictive power and these were again the previous first two variables and a poor response to the first 12 months of lithium. LIMITATIONS: This was a retrospective study; psychosocial stress was not evaluated by standardized criteria; and the predictive value of personality disorders could not be tested thoroughly. CONCLUSIONS: This study suggests that it is possible to predict, rather reliably, the response to prophylactic lithium regarding clinical variables.

Comorbidity of personality disorders with bipolar mood disorders.

The aim of the study was to assess the prevalence of personality disorders in a group of outpatients with bipolar I disorder. The Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) was administered to 90 bipolar outpatients who met the DSM-III-R criteria and 58 control subjects. Of the patients and controls, 47.7% and 15.5%, respectively, had at least one personality disorder. At least one personality disorder in clusters A, B, and C and obsessive-compulsive, paranoid, histrionic, and borderline personality disorders were significantly more prevalent in bipolars. Suicide attempts were more frequent in patients with a history of personality disorder.

Maintenance ECT in a patient with catatonic schizophrenia and tardive dyskinesia.

We describe a 44-year-old-man with a 14-year history of catatonic schizophrenia and a 2-year history of tardive dyskinesia. Because of the worsening course of his illness in recent months, characterized by resistance to antipsychotic drugs and 4 hospitalizations in 7 months with early relapses after inpatient electroconvulsive therapy (ECT), outpatient maintenance ECT was administered. Without receiving any psychotropic medication, the patient's functional capacity was enhanced and he required no hospitalization during a 9-month period of maintenance ECT.

Noradrenergic and serotoninergic depression?

The aim of this study was to test the hypothesis of noradrenergic and serotoninergic depressive subtypes. For this purpose, the correlation between three variables was investigated: urinary 3-methoxy-4-hydroxyphenylglycol (MHPG), dexamethasone suppression test (DST), and clinical response profiles to clomipramine and maprotiline, the effects of which are relatively selective on the uptake of noradrenaline (NA) and 5-hydroxytryptamine (5HT). Our results showed no correlation between these measures. Therefore, the hypothesis of two subtypes of depression was not supported. The only significant finding in this study was the obvious decrease in MHPG excretion during the antidepressant treatment in the group with high pretreatment MHPG.

Spontaneous improvement of tardive dystonia during mania.

Two cases of bipolar affective disorder with tardive dystonic symptoms seemed to improve only with mood elevation, whether the latter occurred spontaneously or was 'induced' pharmacologically. Such cases could prove an interesting locus for the investigation of both affective disorders and tardive dyskinesias.