Clinical insight among persons with schizophrenia spectrum disorders treated with amisulpride, aripiprazole or olanzapine: a semi-randomised trial.

BACKGROUND: Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and above the reduction in symptoms of psychosis. These studies assessed homogeneous samples in terms of stage of illness. Randomised studies investigating a mixed population of first- and multiepisode schizophrenia spectrum disorders might clarify this disagreement. METHODS: Our data were derived from a pragmatic, rater-blinded, semi-randomised trial that compared the effectiveness of amisulpride, aripiprazole and olanzapine. A sample of 144 patients with first- or multiepisode schizophrenia spectrum disorders underwent eight assessments during a 1-year follow-up. Clinical insight was assessed by item General 12 from the Positive and Negative Syndrome Scale (PANSS). We analysed latent growth curve models to test if the medications had a direct effect on insight that was over and above the reduction in total psychosis symptoms. Furthermore, we investigated whether there were differences between the study drugs in terms of insight. RESULTS: Based on allocation analysis, all three drugs were associated with a reduction in total psychosis symptoms in the initial phase (weeks 0-6). Amisulpride and olanzapine were associated with improved insight over and above what was related to the reduction in total psychosis symptoms in the long-term phase (weeks 6-52). However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence. We found no differential effect on insight among those who were antipsychotic-naïve and those who were previously medicated with antipsychotics. CONCLUSIONS: Our results suggest that antipsychotic treatment improves insight, but whether the effect on insight surpasses the effect of reduced total psychosis symptoms is more uncertain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01446328, 05.10.2011.

When does shared decision making is adopted in psychiatric clinical practice? Results from a European multicentric study.

To identify factors associated with the use of shared decision making in routine mental health care in a large multicenter European study. Data have been collected within the study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR), which is a naturalistic, longitudinal, observational study carried out in six European countries. Patients with a severe mental illness attending outpatient units and their treating clinicians have been recruited. Clinicians' Clinical Decision Making (CDM) styles have been explored through the Clinical Decision Making Style Scale. Patients' clinical and social outcomes have been assessed through validated assessment instruments. The sample consisted of 588 patients and 213 professionals. Professionals were mainly psychiatrists (35.7%), nurses (21.6%), support workers, social workers or occupational therapists (24.9%), psychologists (9.9%) or trainees in psychiatry (4.7%). In the majority of cases, clinicians adopted a shared CDM style. Shared CDM was more frequently adopted with patients with psychotic disorders, with a better quality of life and social functioning. At multivariate analyses, the likelihood of adopting shared decision making increased in patients with higher levels of interpersonal relationships' skills (p < 0.05) and global functioning (p < 0.01). On the contrary, being a trainee in psychiatry reduced the likelihood of adopting shared CDM (p < 0.008). Shared decision making has been adopted mainly when patients have a better functioning and less severe clinical symptomatology and by less trained clinicians, differently from national and international recommendations. More efforts should be made to implement interventions to promote shared CDM, with a specific focus for trainees in psychiatry.

Are assisted reproduction technologies associated with categorical or dimensional aspects of psychopathology in childhood, adolescence or early adulthood? Results from a Danish prospective nationwide cohort study.

An increasing number of children are conceived using assisted reproduction technologies (ART), but little is known about the long-term risk in terms of mental health outcomes. All twin and singleton children conceived via ART and born in 1995 were sampled from the Danish in vitro fertilization registry and matched to four spontaneously conceived (SC) children. The children were followed-up at the age of 3, 7, 14 and 18 years in the Danish Psychiatric Central Research Registry, to estimate the prevalence of all possible psychiatric diagnoses; dimensional aspects of psychopathology were assessed at the age of 14 years, using the Child Behavior Checklist (CBCL). The study included 858 ART children and 3436 SC children. ART and SC children were not clinically distinguishable on either the categorical measures of psychopathology at the age of 3, 7, 14 and 18 years, or on CBCL scale scores at the age of 14 years. The findings remained nonsignificant after controlling for sample differences. This large, prospective, nationwide cohort study provides evidence to support that ART exposure does not increase the risk of adverse mental health outcomes considered as a whole, while power was limited to discard an effect of ART on specific mental health disorders.

Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study.

BACKGROUND: Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships. METHOD: A prospective population-based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders. RESULTS: Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19-1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05-1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34-1.76). Findings did not support a dose-response relationship. CONCLUSIONS: Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships.

The gap between available knowledge and its use in clinical psychiatry.

OBJECTIVE: The time span between knowledge becoming available and its integration into daily clinical routine is lengthy. This phenomenon is explored in this study. METHOD: We used the outcomes of our activities for investigating and strengthening the research-based activities to improve physical health in the routines of clinical psychiatric wards as examples for our analyses. RESULTS: The time span between new knowledge becoming available and its implementation into general clinical treatment is very long. However, a shortening of this time span is seen through active leadership backup and clinical research experience among psychiatrists and staff in the wards. In particular, the involvement of medical students interested in clinical research activities seems to have a positive impact. CONCLUSION: Academia needs to be re-implemented into clinical psychiatry. Staff with research experience is needed in all professions to increase evidence-based practice. Leaders must take responsibility for implementing new knowledge into the routines of the department and must support staff in these activities on a daily basis.

Fifty years' development and future perspectives of psychiatric register research.

OBJECTIVE: This article illustrates the development of psychiatric register research and discusses the strengths, limitations, and possible directions for future activities. METHOD: Examples illustrating the development from the post-World War II introduction of psychiatric register research until today are selected. RESULTS: The strengths of register research are seen especially within health service. Until recently, when starting linking registers to biobanks, register research had limited value in cause-seeking. Register research benefits from the possibilities for following identifiable persons over long time (lifelong) and the possibilities for linking to other registers and databases. Important limitations of register research are the heterogeneity and questionable validity of the clinical data collected. CONCLUSION: Future register research can go in the direction of big is beautiful collecting data from all possible sources creating giga-registers. In that case, low data quality will still be an unsolved problem. Or it can take the direction of smaller local clinical databases which has many advantages, for example, integrating clinical knowledge and experience into register research. However, in that case, registers will not be able to deal with rare conditions and diseases.

Widowhood and mortality: a Danish nationwide register-based cohort study.

AIMS: Widowed people have increased mortality compared to married people of the same age. Although most widowed people are of older age, few studies include the oldest old. As life expectancy is increasing, knowledge of widowhood into older age is needed. This study aimed to examine mortality and widowhood in older age by comparing mortality in widowed and married people by sex, age, time since spousal loss and cause of death. METHODS: A Danish register-based matched cohort study of 10% of widowed persons ⩾65 years in the years 2000-2009. For each randomly drawn widowed person, five married persons were matched on sex and age. Mortality rate ratios (MRR) were calculated using Poisson regression, and stratified according to sex and 5-year age intervals. MRRs were furthermore calculated by time since spousal loss and by specific cause of death. RESULTS: The study included 82 130 persons contributing with 642 914.8 person-years. The overall MRR between widowed and married persons with up to 16 years of follow-up was 1.25 (95% CI 1.23-1.28). At age ⩾95 years for men, and ⩾90 years for women, no differences in mortality rates were seen between widowed and married persons. Mortality in widowed persons was increased for most specific causes of death, with the highest MRR from external causes (MRR 1.53 [1.35-1.74]) and endocrine diseases (MRR 1.51 [1.34-1.70]). CONCLUSIONS: Widowhood was associated with increased mortality in older age for both men and women until age ⩾95 and ⩾90 years, respectively. Increased mortality was observed for almost all causes of death.

Participation in medical decision-making across Europe: An international longitudinal multicenter study.

BACKGROUND: The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries. METHODS: The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations. RESULTS: We found large cross-national differences in patients' desire to participate in decision-making, with the center explaining 47.2% of total variance in the desire for participation (P<0.001). Averaged over time and independent of patient characteristics, London (mean=2.27), Ulm (mean=2.13) and Zurich (mean=2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean=1.97), where scores were in turn significantly higher than in Debrecen (mean=1.56). The lowest scores were reported in Naples (mean=1.14). Over time, the desire for participation in decision-making increased significantly in Zurich (b=0.23) and decreased in Naples (b=-0.14). In all other centers, values remained stable. CONCLUSIONS: This study demonstrates that patients' desire for participation in decision-making varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe.

Clinical decision making and outcome in the routine care of people with severe mental illness across Europe (CEDAR).

AIMS: Shared decision making has been advocated as a means to improve patient-orientation and quality of health care. There is a lack of knowledge on clinical decision making and its relation to outcome in the routine treatment of people with severe mental illness. This study examined preferred and experienced clinical decision making from the perspectives of patients and staff, and how these affect treatment outcome. METHODS: "Clinical Decision Making and Outcome in Routine Care for People with Severe Mental Illness" (CEDAR; ISRCTN75841675) is a naturalistic prospective observational study with bimonthly assessments during a 12-month observation period. Between November 2009 and December 2010, adults with severe mental illness were consecutively recruited from caseloads of community mental health services at the six study sites (Ulm, Germany; London, UK; Naples, Italy; Debrecen, Hungary; Aalborg, Denmark; and Zurich, Switzerland). Clinical decision making was assessed using two instruments which both have parallel patient and staff versions: (a) The Clinical Decision Making Style Scale (CDMS) measured preferences for decision making at baseline; and (b) the Clinical Decision Making Involvement and Satisfaction Scale (CDIS) measured involvement and satisfaction with a specific decision at all time points. Primary outcome was patient-rated unmet needs measured with the Camberwell Assessment of Need Short Appraisal Schedule (CANSAS). Mixed-effects multinomial regression was used to examine differences and course over time in involvement in and satisfaction with actual decision making. The effect of clinical decision making on the primary outcome was examined using hierarchical linear modelling controlling for covariates (study centre, patient age, duration of illness, and diagnosis). Analysis were also controlled for nesting of patients within staff. RESULTS: Of 708 individuals approached, 588 adults with severe mental illness (52% female, mean age = 41.7) gave informed consent. Paired staff participants (N = 213) were 61.8% female and 46.0 years old on average. Shared decision making was preferred by patients (χ 2 = 135.08; p < 0.001) and staff (χ 2 = 368.17; p < 0.001). Decision making style of staff significantly affected unmet needs over time, with unmet needs decreasing more in patients whose clinicians preferred active to passive (-0.406 unmet needs per two months, p = 0.007) or shared (-0.303 unmet needs per two months, p = 0.015) decision making. CONCLUSIONS: Decision making style of staff is a prime candidate for the development of targeted intervention. If proven effective in future trials, this would pave the ground for a shift from shared to active involvement of patients including changes to professional socialization through training in principles of active decision making.

Exposure to influenza epidemics during gestation and adult schizophrenia. A 40-year study.

We attempted to replicate earlier findings of an association between exposure to influenza in the second trimester of gestation and adult schizophrenia. The number of live births, of births of future schizophrenics, and of cases of influenza reported to the Ministry of Health in Denmark was ascertained by month from 1911 to 1950. The relationship between fetal exposure to influenza and adult schizophrenia was examined. It is possible that unknown factors produce excesses of both influenza and schizophrenia in the winter, creating an artifactual association. To control for this coincidence, the effects of season were removed from the monthly influenza and schizophrenic birth-rates by several methods. Using the residual scores, it was found that influenza rates higher than seasonally expected, occurring in the sixth month of gestation, were associated with rates of births of schizophrenics greater than seasonally expected. This association was not attributable to some winter-related, third factor or to climatic variables.

Effects on cognitive and clinical insight with the use of Guided Self-Determination in outpatients with schizophrenia: A randomized open trial.

Poor insight has a negative impact on the outcome in schizophrenia; consequently, poor insight is a logical target for treatment. However, neither medication nor psychosocial interventions have been demonstrated to improve poor insight. A method originally designed for diabetes patients to improve their illness management, Guided Self-Determination (GSD), has been adapted for use in patients with schizophrenia (GSD-SZ). The purpose of this study was to investigate the effect on insight of GSD-SZ as a supplement to treatment as usual (TAU) as compared to TAU alone in outpatients diagnosed with schizophrenia. The design was an open randomized trial. The primary hypothesis was cognitive insight would improve in those patients who received GSD-SZ+TAU as assessed by the BCIS. We additionally explored whether the intervention led to changes in clinical insight, self-perceived recovery, self-esteem, social functioning and symptom severity. Assessments were conducted at baseline, and at 3-, 6- and 12-month follow-up. Analysis was based on the principles of intention to treat and potential confounders were taken into account through applying a multivariate approach. A total of 101 participants were randomized to GSD-SZ+TAU (n=50) or to TAU alone (n=51). No statistically significant differences were found on the cognitive insight. However, at 12-month follow-up, clinical insight (measured by G12 from the Positive and Negative Syndrome Scale), symptom severity, and social functioning had statistically significantly improved in the intervention group as compared to the control group. "Improving insight in patients diagnosed with schizophrenia", NCT01282307, http://clinicaltrials.gov/.

European Psychiatric Association (EPA) guidance on quality assurance in mental healthcare.

PURPOSE: To advance the quality of mental healthcare in Europe by developing guidance on implementing quality assurance. METHODS: We performed a systematic literature search on quality assurance in mental healthcare and the 522 retrieved documents were evaluated by two independent reviewers (B.J. and J.Z.). Based on these evaluations, evidence tables were generated. As it was found that these did not cover all areas of mental healthcare, supplementary hand searches were performed for selected additional areas. Based on these findings, fifteen graded recommendations were developed and consented by the authors. Review by the EPA Guidance Committee and EPA Board led to two additional recommendations (on immigrant mental healthcare and parity of mental and physical healthcare funding). RESULTS: Although quality assurance (measures to keep a certain degree of quality), quality control and monitoring (applying quality indicators to the current degree of quality), and quality management (coordinated measures and activities with regard to quality) are conceptually distinct, in practice they are frequently used as if identical and hardly separable. There is a dearth of controlled trials addressing ways to optimize quality assurance in mental healthcare. Altogether, seventeen recommendations were developed addressing a range of aspects of quality assurance in mental healthcare, which appear usable across Europe. These were divided into recommendations about structures, processes and outcomes. Each recommendation was assigned to a hierarchical level of analysis (macro-, meso- and micro-level). DISCUSSION: There was a lack of evidence retrievable by a systematic literature search about quality assurance of mental healthcare. Therefore, only after further topics and search had been added it was possible to develop recommendations with mostly medium evidence levels. CONCLUSION: Evidence-based graded recommendations for quality assurance in mental healthcare were developed which should next be implemented and evaluated for feasibility and validity in some European countries. Due to the small evidence base identified corresponding to the practical obscurity of the concept and methods, a European research initiative is called for by the stakeholders represented in this Guidance to improve the educational, methodological and empirical basis for a future broad implementation of measures for quality assurance in European mental healthcare.

Relationship between in utero exposure to influenza epidemics and risk of schizophrenia in Denmark.

Several recent epidemiological studies suggest that exposure to influenza during gestation increases the risk of later developing schizophrenia. Inconsistency exists, however, particularly in studies that have examined the relationship between the prevalence of influenza and the monthly number of schizophrenic births, over many years. Our sample (N = 9462) was obtained from a Danish computerized case register, and consisted of schizophrenia patients born between 1915 and 1970, and first admitted to Danish psychiatric hospitals between 1971 and 1991. The study sample was chosen to represent "incidence cases" to allow us to calculate the population attributable risk fraction (PAF). The temporal correlation of fluctuations in the prevalence of influenza and fluctuations in the monthly number of preschizophrenic births was examined using a Poisson regression analysis. Exposure to influenza 4 months prior to birth (i.e., about the 6th month of gestation) was significantly associated with an increased risk of later schizophrenia, especially for narrowly defined schizophrenia. The number of schizophrenic births was found to have risen by 12% (95% confidence interval: 1-24%) for every 100,000 cases of influenza in the 4th month before birth. Our model indicates the PAF to be 1.4%, that is, only 1.4% of the whole schizophrenic sample is attributed to prenatal exposure to influenza. Although maternal exposure to influenza during midgestation is not a major risk factor for schizophrenia, the elucidation of its causal mechanism may open the avenue to understanding the neurodevelopmental origins of the disease.

Hospitalization patterns in schizophrenia. A 13-year follow-up.

All first admitted patients in 1972 from a catchment area of 582,000 inhabitants aged 15 years or more who were diagnosed as schizophrenic at least once from 1972 until September 1983 (n = 53) were followed-up on average 13 years after first admission. About 20% of the cohort was hospitalized on any given day throughout the length of the follow-up period. The duration of hospitalization decreased from a mean of 8.2 months for the first admission to 1.7 months for the tenth or later admission. The readmission risk increased as a function of the number of previous admissions. Patients with income from occupation or from grants for education had shorter duration of first in-patient period. If the patients were diagnosed as schizophrenics already during the first hospitalization the risk for prolonged duration of the first in-patient period was increased but the readmission risk diminished. Furthermore, readmission risk after the first discharge was diminished by own income and by out-patient treatment and increased by low social status. High proportion of follow-up time in hospital (greater than or equal to 30%) was correlated to affective flattening present at first admission. Of the cohorts' total number of admissions (n = 493) 12% were involuntary. Involuntary admissions were more frequent in the first half of the follow-up period and were correlated to a previous involuntary admission.

Causes and consequences of the gender difference in age at onset of schizophrenia.

The ABC (age, beginning, course) schizophrenia study was commenced in 1987 to generate and test hypotheses about pathogenic aspects of schizophrenia. One of the main branches of the study focused on how gender influences the age distribution of onset, symptomatology, illness behavior, and early course in schizophrenia. Proceeding from one of the rare, strikingly deviating, consistent findings--the gender difference in age at first admission--we launched a systematic search for explanations by generating and testing hypotheses in a series of substudies. We moved from the epidemiological to the neurobiological and finally to the clinical level. The present article is an attempt to provide a brief overview of the individual stages of the ABC study and the different levels of investigation involved in formulating and testing the estrogen hypothesis in animal experiments and in demonstrating its applicability to human schizophrenia. From these results, three hypotheses were formulated and tested on data from an ABC study sample of 232 first-episode cases of schizophrenia. The analyses described here represent the latest stages of the ABC study.