The relationship between childhood trauma, psychotic symptoms, and cognitive schemas in patients with schizophrenia, their siblings, and healthy controls: results from the EU-GEI study.

BACKGROUND: The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms. METHODS: Seven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale. RESULTS: Patients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood emotional abuse and neglect were more common in siblings than controls. CT was related to negative cognitive schemas toward self/others in patients, siblings, and controls. We found that negative schemas about self-mediated the relationship between emotional abuse and thought withdrawal and thought broadcasting. Approximately 33.9% of the variance in these symptoms was explained by the mediator. It also mediated the relationship between sexual abuse and persecutory delusions in SCZ. CONCLUSIONS: Our findings suggest that childhood abuse and neglect are more common in patients with schizophrenia than their siblings and healthy controls, and have different impacts on clinical domains which we searched. The relationship between CT and positive symptoms seems to be mediated by negative cognitive schemas about self in schizophrenia.

A replication study of JTC bias, genetic liability for psychosis and delusional ideation.

BACKGROUND: This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. METHODS: Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. RESULTS: JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46-5.17 for siblings and aRR: 5.07 CI 95% 4.13-6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67-8.51, and in patients: 2.15 CI 95% 0.94-4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. CONCLUSIONS: These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.

BACKGROUND: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. METHODS: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. RESULTS: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). CONCLUSIONS: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study.

BACKGROUND: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. METHODS: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. RESULTS: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. CONCLUSIONS: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

The epidemiology of alcohol use in Izmir, Turkey: drinking pattern, impairment and help-seeking.

PURPOSE: There is no report on various patterns of alcohol drinking and related impairment, help-seeking in Turkey. We investigated the 12-month prevalence and correlates of drinking patterns and alcohol use disorders in the general population of Izmir-Turkey, with further analyses on role impairment and help-seeking. METHOD: A multi-stage clustered area probability sample of adult household residents in the Izmir Metropolitan Area was assessed using the Composite International Diagnostic Interview 2.1 (n  = 4011). Estimation focused on prevalence and correlates of 12-month drinking pattern and DSM-IV alcohol use disorders. The 12-month drinking pattern included groups of non-regular users, regular non-heavy drinkers, regular heavy drinkers, and alcohol abuse disorder and alcohol dependence. All respondents were questioned about receiving 12-month treatment for any psychological complaints, the route of help-seeking, and were assessed with Short Form-36 for functional impairments. Multinomial logistic regression was used for underlying associations between the covariates and the drinking patterns. RESULTS: The rate of lifetime alcohol abstinence was 52.3% while the prevalence of past-year users was 14.8%. The 12-month prevalence estimates of regular heavy drinkers, and alcohol abuse disorder and dependence were 2.5%, 3.2 and 1.6%, respectively. Any of the drinking patterns and alcohol use disorders was associated with male gender, and higher levels of education, monthly income and socioeconomic status. Alcohol dependence was associated with mental health impairment but not with physical impairment. The 12-month rates of help-seeking in alcohol abuse and dependence were 11.6 and 16.5%. CONCLUSION: Although alcohol use disorders are lower than estimates of Western countries, alcohol use constitute a major reason of disability with prominent treatment gap.

Relation of formal thought disorder to symptomatic remission and social functioning in schizophrenia.

OBJECTIVE: The aim of this cross-sectional study is to examine the relation of formal thought disorder (FTD) with symptomatic remission (SR) and social functioning in patients with schizophrenia. METHOD: The study was carried out with a sample consisting of 117 patients diagnosed with schizophrenia according to DSM-IV. The patients were assessed with the Positive and Negative Syndrome Scale (PANSS), the Thought and Language Index (TLI), and the Personal and Social Performance Scale (PSP). We used logistic regression in order to determine the relation between FTD and SR and linear regression to identify the strength of association between FTD and social functioning. RESULTS: Logistic regression analysis revealed that poverty of speech (odds ratio: 1.47, p<0.01) and peculiar logic (odds ratio: 1.66, p=0.01) differentiated the remitted patients from the non-remitted ones. Linear regression analysis showed that the PSP total score was associated with poverty of speech and peculiar logic items of the TLI (B=-0.23, p<0.01, B=-0.24, p=0.01, respectively). CONCLUSION: Our findings suggest that poverty of speech and peculiar logic are the specific domains of FTD which are related to both SR status and social functioning in patients with schizophrenia.

Formal thought disorder in first-episode psychosis.

Formal thought disorder (FTD) is one of the fundamental symptom clusters of schizophrenia and it was found to be the strongest predictor determining conversion from first-episode acute transient psychotic disorder to schizophrenia. Our goal in the present study was to compare a first-episode psychosis (FEP) sample to a healthy control group in relation to subtypes of FTD. Fifty six patients aged between 15 and 45years with FEP and forty five control subjects were included in the study. All the patients were under medication for less than six weeks or drug-naive. FTD was assessed using the Thought and Language Index (TLI), which is composed of impoverishment of thought and disorganization of thought subscales. FEP patients showed significantly higher scores on the items of poverty of speech, weakening of goal, perseveration, looseness, peculiar word use, peculiar sentence construction and peculiar logic compared to controls. Poverty of speech, perseveration and peculiar word use were the significant factors differentiating FEP patients from controls when controlling for years of education, family history of psychosis and drug abuse.

Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

BACKGROUND: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. RESULTS: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. CONCLUSIONS: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.

Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study.

BACKGROUND: Social cognition impairments, such as facial emotion recognition (FER), have been acknowledged since the earliest description of schizophrenia. Here, we tested FER as an intermediate phenotype for psychosis using two approaches that are indicators of genetic risk for schizophrenia: the proxy-genetic risk approach (family design) and the polygenic risk score for schizophrenia (PRS-SCZ). METHODS: The sample comprised 2039 individuals with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). The Degraded Facial Affect Recognition Task (DFAR) was applied to measure the FER accuracy. Schizotypal traits in siblings and HC were assessed using the Structured Interview for Schizotypy-Revised (SIS-R). The PRS-SCZ was trained using the Psychiatric Genomics Consortium results. Regression models were applied to test the association of DFAR with psychosis risk, SIS-R, and PRS-SCZ. RESULTS: The DFAR-total scores were lower in individuals with schizophrenia than in siblings (RR = 0.97 [95% CI 0.97, 0.97]), who scored lower than HC (RR = 0.99 [95% CI 0.99-1.00]). The DFAR-total scores were negatively associated with SIS-R total scores in siblings (B = -2.04 [95% CI -3.72, -0.36]) and HC (B = -2.93 [95% CI -5.50, -0.36]). Different patterns of association were observed for individual emotions. No significant associations were found between DFAR scores and PRS-SCZ. CONCLUSIONS: Our findings based on a proxy genetic risk approach suggest that FER deficits may represent an intermediate phenotype for schizophrenia. However, a significant association between FER and PRS-SCZ was not found. In the future, genetic mechanisms underlying FER phenotypes should be investigated trans-diagnostically.

The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples.

[The psychosis epidemiology in Turkey: a systematic review on prevalence estimates and admission rates]. / Türkiye'de Psikoz Epidemiyolojisi: Yayginlik Tahminleri ve Basvuru Oranlari Üzerine Sistematik Bir Gözden Geçirme.

OBJECTIVE: To provide prevalence estimate, admission rates and related features of psychotic disorders in Turkey. METHOD: Studies with data on prevalence and/or rates in outpatient or inpatient admissions after 1990 were included. Strings of ([schizo*OR psych*] AND Turkey) were used in PubMed and PsychINFO to detect relevant studies. Turkish Medical and Psychiatry indexes were screened with Turkish keywords. Abstract books of national congresses, national index of thesis, and references of the included papers were searched for additional data. Results were presented as prevalence per 1000 and median values of admission rates. RESULTS: A total of 56 studies were included, including 8 cross-sectional (4 core and 4 special group), 27 outpatient and 21 inpatient admission estimates or rates. The lifetime prevalence of schizophrenia in general population (pooled data, n: 6022) was 8.9 per 1000 (Standard error [SE]: 1.2; 95% confidence interval [CI]: 6.6-11.3). Psychosis prevalence is higher in subgroups including university students, prisoners and homeless people. Patients with a diagnosis of psychotic disorder constituted 7.6% and 26.9% of adult outpatient and inpatient psychiatry admissions. However, median rates vary depending on institutional, regional, temporal and residential features. Male gender was at higher risk in all kinds of estimates and rates for all age groups. CONCLUSION: Prevalence of schizophrenia in Turkey is higher than the formerly reported estimates in different countries. Higher prevalence may be a consequence of sample properties, environmental risk exposures, and study design. However more research is needed to further elaborate the relatively higher prevalence. Nevertheless, a major part of the psychiatry services are devoted to psychotic outpatients and inpatients.

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

BACKGROUND: A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate. RESULTS: ES-SCZ was associated with the GAF dimensions in patients (symptom: B = -1.53, p-value = 0.001; disability: B = -1.44, p-value = 0.001), siblings (symptom: B = -3.07, p-value < 0.001; disability: B = -2.52, p-value < 0.001), and healthy controls (symptom: B = -1.50, p-value < 0.001; disability: B = -1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group. CONCLUSIONS: Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Prevalence and risk factors of psychotic symptoms: in the city of Izmir, Turkey.

BACKGROUND: Psychotic symptoms, psychotic-like experiences and schizotypal signs can emerge in different socio-cultural circumstances and cause clinical or non-clinical pictures. Transient or self-limiting psychotic-like experiences are more prevalent than clinical psychotic disorders. The aim of this study is to determine the prevalence and sociodemographic correlates of psychotic symptoms in an urban area. METHODS: A cross-sectional study was conducted among the residents of two districts in the urban area of Izmir, Turkey. Among the systematically selected 1,500 residents of 85,212-study population, a total of 1,268 individuals (response rate: 84.5%) were screened for any lifetime psychotic symptoms. RESULTS: Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms. CIDI (+) psychotic symptoms were found in 3.6% of the screened sample. Logistic regression analysis showed that being a female (OR=2.4, 95% CI=1.2-5.1), having a first degree family history of any mental disorders (OR=13.9, 95% CI=5.7-34.3), lack of social support (OR=4.5, 95% CI=2.3-8.6) and alcohol use (OR=4.9, 95% CI=2.3-10.6) were all related to psychotic symptoms. CONCLUSION: Prevalence of any psychotic symptom is lower compared to European studies. Alcohol might be considered as a risk factor for developing psychotic symptoms in the Turkish cultural setting.

[Attitudes and behaviors of psychiatry residents and psychiatrists working in training institutes towards the relationship between the pharmaceutical industry and physicians]. / Egitim Veren Kurumlarda Calisan Psikiyatristlerin.

OBJECTIVE: To determine the attitudes and behaviors of psychiatrists and psychiatry residents towards pharmaceutical representatives and their promotional activities, and to evaluate the effect of the duration of residency and type of the training institution on these attitudes and behaviors. METHOD: A validated questionnaire for assessing the attitudes and behaviors of physicians towards the pharmaceutical industry was administered to psychiatrists and psychiatry residents at regional meetings. Of the 1973 participants, 348 responded. RESULTS: Although there was significant interaction between psychiatrists and pharmaceutical representatives, 50.7% of psychiatrists reported that they thought these interactions had no impact on their prescribing practices. First- and second-year residents agreed more than the other residents and the specialist that pharmaceutical representatives provided accurate information and had no effect on physician prescribing practices. First- and second-years residents agreed less than older residents that pharmaceutical representatives used marketing techniques. The psychiatrists regarded most of the pharmaceutical promotions as appropriate. State hospital staff agreed more than the university hospital staff that the pharmaceutical industry should support educational meetings in their institutions. CONCLUSION: There was intense interaction (3/4)characterized by undefined boundaries (3/4)between psychiatrists and the pharmaceutical industry. Most physicians were not provided any guidelines concerning their interactions with pharmaceutical representatives and there was general concern about the necessity of restricting these interactions.

Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study.

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome.

White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Introduction: White noise speech illusions index liability for psychotic disorder in case-control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02-1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79-1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85-1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09-1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84-1.05; ORlow cognitive ability 1.43, 95% CI 1.23-1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82-1.04; ORhigh adversity 1.31, 95% CI 1.13-1.52). A similar, although less marked, pattern was seen for categorical patient-control and sibling-control comparisons. Exposure to recent life events did not modify the association between white noise and familial risk (p interaction = 0.232). Conclusion: The association between white noise speech illusions and familial risk is contingent on additional evidence of endophenotypic expression and of exposure to childhood adversity. Therefore, speech illusions may represent a trait-dependent risk marker.

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study.

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures.

[Financial conflict of interest in clinical psychiatry studies: a review]. / Klinik psikiyatri arastirmalarinda maddi çikar çatismasi: bir gözden geçirme.

Pharmaceutical industry revenues from global pharmaceutical sales have increased 7% to $602 billion in 2005. Approximately 15% of these revenues were spent on clinical research and drug development studies. Because of the huge budget allocated to research and development studies the number of studies being conducted by pharmaceutical companies has increased. The impact of the pharmaceutical industry on clinical trials has been affected by financial conflicts of interest between researchers and the industry. Conflict of interest refers to a situation in which it appears that a researcher's personal financial interest could significantly affect the design, conduct, and/or reporting of such research. Financial conflict of interest has been reported to be frequent in clinical trials in general medicine. It is estimated that 89%-98% of comparative drug treatment studies are funded by pharmaceutical companies. It was reported that favorable outcomes for the firms conducting these studies were significantly more common in industry-funded studies than in non-industry funded ones. These biased outcomes were due to conscious or unconscious decisions about the design, data analysis, and publishing of the studies. Biased outcomes of industry-funded studies have diminished the integrity of academic institutions, pharmaceutical companies, researchers, and scientific journals; therefore, various precautions have been taken in order to reduce the effect of conflict of interest on study outcomes. The aim of this review was to evaluate the effect of conflict of interest on outcomes in clinical psychiatry studies.