European Schizophrenia Cohort Research Articles

Longitudinal symptomatic interactions in long-standing schizophrenia: a novel five-point analysis based on directed acyclic graphs.

Recent network models propose that mutual interaction between symptoms has an important bearing on the onset of schizophrenic disorder. In particular, cross-sectional studies suggest that affective symptoms may influence the emergence of psychotic symptoms. However, longitudinal analysis offers a more compelling test for causation: the European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. We predicted that the persistence of psychotic symptoms would be driven by the continuing presence of affective disturbance. EuroSC included 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures of psychotic and affective symptoms were repeated four times at 6-month intervals, thereby furnishing five time-points. To examine interactions between symptoms both within and between time-slices, we adopted a novel technique for modelling longitudinal data in psychiatry. This was a form of Bayesian network analysis that involved learning dynamic directed acyclic graphs (DAGs). Our DAG analysis suggests that the main drivers of symptoms in this long-term sample were delusions and paranoid thinking. These led to affective disturbance, not vice versa as we initially predicted. The enduring relationship between symptoms was unaffected by whether patients were receiving first- or second-generation antipsychotic medication. In this cohort of people with chronic schizophrenia treated with medication, symptoms were essentially stable over long periods. However, affective symptoms appeared driven by the persistence of delusions and persecutory thinking, a finding not previously reported. Although our findings as ever remain hostage to unmeasured confounders, these enduring psychotic symptoms might nevertheless be appropriate candidates for directly targeted psychological interventions.

The mediating role of depression in pathways linking positive and negative symptoms in schizophrenia. A longitudinal analysis using latent variable structural equation modelling.

The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms. We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months. We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct. Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

Positive and negative symptoms in schizophrenia: A longitudinal analysis using latent variable structural equation modelling

BackgroundRecent network models of schizophrenia propose it is the consequence of mutual interaction between its symptoms. While cross-sectional associations between negative and positive symptoms are consistent with this idea, they may merely reflect their involvement in the diagnostic process. Longitudinal analyses however may allow the identification of possible causal relationships. The European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. MethodsEuroSC includes 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures were repeated after 12 and 24 months. Latent variable structural equation modelling was used to investigate the direction of effect between positive and negative symptoms assessed with the Positive and Negative Syndrome Scale, controlling for the effects of depressed mood and antipsychotic medication. ResultsThe structural model provided acceptable overall fit [χ2 (953) = 2444.32, P < 0.001; CFI = 0.909; RMSEA = 0.046 (90% CI: 0.043, 0.048); SRMR = 0.052]. Both positive and negative symptoms were persistent, and strongly auto-correlated. There were also persistent cross-sectional associations between positive and negative symptoms. While the path from latent positive to negative symptoms from T1 to T2 approached conventional levels of statistical significance (P = 0.051), that from T2 to T3 did not (P = 0.546). Pathways in the reverse direction were uniformly non-significant. ConclusionsThere was no evidence that negative symptoms predict later positive symptoms. The prediction of negative symptoms by positive symptoms was ambiguous. We discuss implications for conceptualization of schizophrenic processes.

Utility decrements associated with side effects in schizophrenia

Objective:Most of the existing studies investigating the impact of schizophrenia on utility have focused on the different stages of the disease. The objective of this study was to describe and quantify the impact of treatment-related side-effects on utility in patients with schizophrenia, using data from an observational study.Methods:This study used data from the European Schizophrenia Cohort (EuroSC), a multi-center 2-year cohort study conducted in France, England, and Germany. The EQ-5D questionnaire was completed every 6 months, as well as the Subjective Side Effect Rating Scale, assessing patient distress over extrapyramidal symptoms (EPS), weight gain, sedation, and sexual dysfunction, used to assess whether or not the patient experienced the side-effect. At first a bivariate analysis was conducted to describe utility values with and without side-effects. Then, a random effects regression analysis was performed on utility, where random effects were controlled for repeated measures on the same subjects, with potential confounding factors. Finally, findings were compared with those of previous publications.Results:This sample consisted of 1208 patients with schizophrenia. At the baseline visit, the most reported side-effect was EPS (almost 60% of patients), followed by sedation and weight gain (∼50% of patients for each), and sexual dysfunction (almost 30% of patients). Significant association with severity of symptoms, functioning abilities, and utility were found. Patients reporting none of the studied side-effects had an average EQ-5D index score of 0.81, found to be higher than scores of patients reporting EPS (0.70), sexual dysfunction (0.67), sedation (0.70), or weight gain (0.72). The random effects model reported a utility decrement of 0.042 for EPS, 0.022 for weight gain, 0.022 for sexual dysfunction, and 0.019 for sedation. Although the external validation was difficult due to the different methods or definitions of the side-effects, as well as the paucity of data for weight gain, sedation and sexual dysfunction, the results were generally consistent with previous studies.Conclusion:This study aimed at quantifying the direct impact of main side-effects associated with antipsychotics on patients’ utility. Results suggested a significant direct impact of side-effects, with EPS being the most impactful.

The lifetime and past-year prevalence of dual diagnosis in people with schizophrenia across Europe: findings from the European Schizophrenia Cohort (EuroSC)

Relatively little is known about rates of comorbid drug and alcohol problems in people with schizophrenia outside the USA. Most studies have recruited from single countries. Newly available data provided an unmatched opportunity to investigate the prevalence of comorbid dependence on alcohol and other psychoactive substances in people with schizophrenia in France, Germany and the UK at the same time. The European Schizophrenia Cohort study data set used semi-structured clinical interviews to establish DSM-IV diagnoses. 1,208 patients were interviewed in nine centres. The lifetime rate for comorbid dependence on any substance was highest in the UK (35 %), but considerably lower in Germany (21 %) and in France (19 %), and generally more than double the past-year rates. Dependence on alcohol and on other psychoactive substances showed similar variations (comorbid alcohol dependence: UK 26 %; Germany 18 %; France 14 %; comorbid drug dependence: UK 18 %; Germany 8 %; France 7 %). Differences within countries persisted after controlling for individual characteristics. The relative odds of dependence were higher than in the general population, but varied between countries and centres. Dependence disorders are a common problem in people with schizophrenia in Western Europe, although effective service configurations have yet to be developed. Overall, these European rates are less than those reported from the USA. Research comparing people with current comorbidity with those who are no longer dependent is needed.

Direct medical mental health care costs of schizophrenia in France, Germany and the United Kingdom – Findings from the European Schizophrenia Cohort (EuroSC)

Objectives To quantify and compare the resource consumption and direct costs of medical mental health care of patients suffering from schizophrenia in France, Germany and the United Kingdom. Methods In the European Cohort Study of Schizophrenia, a naturalistic two-year follow-up study, patients were recruited in France (N = 288), Germany (N = 618), and the United Kingdom (N = 302). Data about the use of services and medication were collected. Unit cost data were obtained and transformed into United States Dollar Purchasing Power Parities (USD-PPP). Mean service use and costs were estimated using between-effects regression models. Results In the French/German/UK sample estimated means for a six-month period were respectively 5.7, 7.5 and 6.4 inpatient days, and 11.0, 1.3, and 0.7 day-clinic days. After controlling for age, sex, number of former hospitalizations and psychopathology (CGI score), mean costs were 3700/2815/3352 USD-PPP. Conclusions Service use and estimated costs varied considerably between countries. The greatest differences were related to day-clinic use. The use of services was not consistently higher in one country than in the others. Estimated costs did not necessarily reflect the quantity of service use, since unit costs for individual types of service varied considerably between countries.

Side‐effects of antipsychotic medication and health‐related quality of life in schizophrenia

This analysis used data from the large (n = 1208) European Schizophrenia Cohort to examine the association between subjective side-effects of antipsychotic medication and the Mental and Physical Composite Scores (MCS; PCS) of the SF-36 scale. Relationships between the subjective evaluation of side-effects identified from the Subjective Side-Effects Scale and the adjusted mean score on the PCS and MCS were examined. Where appropriate, these associations of subjective side-effects were compared with those of the same side-effects measured objectively. In this study, subjective side-effects of antipsychotic medication were linked either to both the PCS and the MCS or, in a few instances, to neither. Subjective evaluations of sexual side-effects were associated only with the MCS, those of sialorrhoea only with the PCS. Objective ratings of extrapyramidal side-effects were related neither to PCS nor to MCS. These data suggest that side-effects, whether subjective or objective, may need to be considered individually in relation to their impact on quality of life.

Correlates of Subjective Quality of Life in People With Schizophrenia

Quality of life (QOL) is an important outcome for people with schizophrenia, but most previous studies of its correlates have had small sample sizes or explored a limited number of variables. We conducted an analysis of the baseline data from the European Schizophrenia Cohort (EuroSC) study, a naturalistic investigation of people with schizophrenia living in France, Germany, and the United Kingdom (N = 1208). German participants had the highest subjective QOL. Country of residence, depression, accommodation status, and employment were the most important factors in explaining subjective QOL. Many correlates of subjective QOL in people with schizophrenia were similar to those in the general population. Many of the factors important in explaining subjective QOL in people with schizophrenia are not readily amenable to change. Differences in mental health service provision in the United Kingdom and Germany may in part explain variations in the QOL of people with schizophrenia resident there.

Urban residence, victimhood and the appraisal of personal safety in people with schizophrenia: results from the European Schizophrenia Cohort (EuroSC)

Patients with schizophrenia are at increased risk of being victims of violent and non-violent crimes. We have determined how the experience of crime and subjective feelings of safety differ between urban and rural residential areas. We analysed data from the European Schizophrenia Cohort (EuroSC), a 2-year follow-up study of 1208 patients in the UK, France and Germany. Subjective safety and a history of victimhood were elicited with Lehman's Quality of Life Inventory. Regression models adjusted the effects of living environment for country, education, employment, financial situation, drug and alcohol abuse, criminal arrests and the level of schizophrenic symptoms. Ten per cent of patients were victims of violent and 19% of non-violent crimes. There was no significant relationship between victim status and residential area. However, subjective safety was clearly worse in cities than in rural areas. Aspects of objective and subjective safety were related to different factors: being the victim of violence was most strongly associated with alcohol and drug abuse and with criminal arrests of the patients themselves, whereas impaired subjective safety was most strongly associated with poverty and victimhood experience. Although urban living was not associated with increased objective threats to their security, patients did feel more threatened. Such stress and anxiety can be related to concepts of social capital, and may contribute unfavourably to the course of the illness, reflecting the putative role of appraisal in cognitive models of psychosis. Securing patients' material needs may provide a way to improve subjective safety.

Rates and correlates of employment in people with schizophrenia in the UK, France and Germany

Little is known about international variations in employment rates among people with schizophrenia or about the factors associated with employment in this disorder. To describe employment patterns and the variables associated with working in an international sample of people with schizophrenia. An analysis was made of baseline data from the European Schizophrenia Cohort study, a 2-year investigation of people with schizophrenia in contact with secondary services and living in France, Germany and the UK (n=1208). Participants were working in all sections of the job market. People who had a degree, were living with their families or had experienced only a single episode of illness were more likely to be working. A continuous illness course, more severe non-psychotic symptoms and drug misuse reduced the odds of employment. There were large variations between centres in employment rates, which were highest in the three German study sites. These differences persisted after adjustment for individual characteristics. Local social contexts may be as important as individual or illness-related factors in explaining employment status.

A prospective study of Quality of life in schizophrenia in three European countries

Only a small number of studies have tried to identify factors influencing the subjective QoL of patients suffering from schizophrenia in a longitudinal design. These studies suffer from small clinical samples or compare baseline data only with a single follow-up. The European Schizophrenia Cohort Study overcomes these shortcomings by providing data from five time points on 1208 patients in psychiatric treatment in three European countries over a period of 2 years. QoL was measured with the brief version of Lehman's Quality of Life Interview. Random effects, between-effects and within-effects regression models were computed in order to measure the influence on subjective QoL of patients' socio-demographic and clinical characteristics and objective QoL. Objective QoL scores were generally found to be related to the equivalent subjective QoL scores. People's financial situation, and depressive and positive symptoms had a general effect on almost all subjective domains. The significant effects of objective finances on subjective domains like health and social relations raise interesting possibilities for intervention. Sufficient financial resources appear to be a necessary condition for achieving satisfactory QoL in schizophrenia patients. However, changes in individual's characteristics and circumstances did not relate as strongly as expected to changes in QoL, suggesting effective intervention may be difficult.

The social context of insight in schizophrenia.

Psychiatrists place great weight on impaired insight in schizophrenia, generally attributing it to pathological mental processes. However, denial of illness may be based on attitudes common in patients' social and cultural groups. Moreover, even where denial of illness has a pathological element, it may be affected by the social context. In this paper, we predicted that denial of illness would be associated with social distance between clinician and patient, and reduced by access to 'normalizing' social interaction. One hundred and fifty patients with schizophrenia in the London arm of the European Schizophrenia cohort were assessed using the 'Awareness of Illness' (AI) subscale of David's Assessment of Insight. Clinical and social attributes were related to AI. There was little evidence for our social distance hypotheses: there was little variation in AI by social class, ethnicity, membership of a drug taking culture or the presence of strongly held religious beliefs. However, there were strong relations between AI and the size of primary group, consistent with our normalizing hypothesis. The normalizing function of social support is in line with modern psychological models of delusion formation. Longitudinal data will eventually be available from the current study that will assist in establishing the causal direction of this association.