Update to the study protocol Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial.

We unfortunately need to make an update to our published study protocol that describes a significant change in the design of the study. The Committee on Health Research Ethics of the Capital Region Denmark recently rejected the approval of changing the primary outcome in the trial, on the invariable grounds that the trial has already commenced. It is therefore necessary to retain the Green Paranoid Thought Scale (GPTS) part B, ideas of persecution, as our primary outcome, and GPTS part A, ideas of social reference, as a secondary outcome, which is described opposite in our published study protocol. The exchange of outcomes has not affected participation in our trial or the informed consent. Intervention in both groups and assessments are unchanged. The two outcomes together constitute GPTS and the unifying concept we attempt to treat, namely paranoid ideations. As this is a blinded, methodologically rigorous trial, we did not have-and still do not have-access to preliminary data, and therefore, we have no knowledge of the distribution of our two intervention groups nor the potential effect of the intervention. The power calculation remains unchanged irrespective of the selection of the primary outcome. We have been fully transparent with the changes in primary and secondary outcomes on ClinicalTrials.gov throughout the trial. Due to the considerations mentioned above, we assumed that there would not be any ethical implications of the change of primary outcome. We sincerely apologize for the irregularity caused because of this assumption.Trial registrationClinicalTrials.gov NCT04902066 . Initial release April 19th, 2021.

The CHALLENGE trial: the effects of a virtual reality-assisted exposure therapy for persistent auditory hallucinations versus supportive counselling in people with psychosis: study protocol for a randomised clinical trial.

BACKGROUND: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations in spite of treatment with antipsychotic medication. The aim of this trial is to examine the effect of a targeted virtual reality therapy for persistent auditory hallucinations in individuals with psychosis. The trial explores whether this type of therapy can decrease the severity, frequency and distress of auditory hallucinations and, additionally, whether it can reduce clinical symptoms and enhance daily functioning in individuals with psychosis. METHODS: The study is a randomised, assessor-blinded parallel-group superiority clinical trial, allocating a total of 266 patients to either the experimental intervention or supportive counselling. The participants will be randomised to either (1) seven sessions of virtual reality therapy or (2) seven sessions of supportive counselling to be delivered within the first 12 weeks after inclusion in the study. All participants will be assessed at baseline and 12 and 24 weeks post-baseline. Independent assessors blinded to the treatment allocation will evaluate the outcome. The primary outcome is the level of auditory hallucinations measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH) total score at the cessation of treatment at 12 weeks. Secondary outcomes are frequency of auditory hallucinations, the distress caused by auditory hallucinations, perceived voice power, patient acceptance of voices, patients' ability to respond to voices in an assertive way and social and daily function. DISCUSSION: Promising evidence of the efficacy of this immersive virtual reality-based therapy for auditory hallucinations exist, but evidence needs to be established in a large, methodological rigorous trial. If the therapy proves to be beneficial in reducing the severity of refractory auditory hallucinations, a large group of patients with schizophrenia and related disorders could be the target group of this short-term psychotherapeutic intervention.

Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial.

BACKGROUND: Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral therapy (CBT) for psychosis show small to moderate effect sizes in reducing paranoid ideations. Virtual reality-based CBT (VR-CBT) could improve therapy efficacy as exposure and behavioral experiments in VR can be optimized, individualized, and carried out in a safe environment. Few VR-CBT studies exist for paranoid ideations and there is a need for large-scale, methodologically rigorous trials. METHODS: This study is a randomized, assessor-blinded parallel-groups multi-center superiority clinical trial, fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients diagnosed with schizophrenia spectrum disorder, including schizotypal disorder (ICD-10 F20-29), will be allocated to either 10 sessions of symptom-specific CBT-VR plus treatment as usual-versus 10 sessions of standard symptom-specific CBT for paranoid ideations (CBT) plus treatment as usual. All participants will be assessed at baseline, treatment end (3 months post baseline), and then 9 months post baseline. A stratified block-randomization with concealed randomization sequence will be conducted. Independent assessors blinded to the treatment will evaluate the outcome. Analysis of outcome will be carried out with the intention to treat principles. The primary outcome is ideas of social reference measured with Green Paranoid Thought Scale Part A (GPTS-A) at the cessation of treatment at 3 months post baseline. Secondary outcomes are ideas of persecution (GPTS-B), Social Interaction Anxiety Scale (SIAS), Personal and Social Performance scale (PSP), Safety Behavior Questionnaire (SBQ), and CANTAB Emotion Recognition Task. DISCUSSION: The trial will elucidate whether VR-CBT can enhance therapy efficacy for paranoid ideations. Additionally, Trial findings will provide evidence on the effectiveness and cost-effectiveness of VR-CBT for paranoid ideations that can guide the possible dissemination and implementation into clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04902066 . Initial release April 9th, 2021.

EPA guidance on treatment of negative symptoms in schizophrenia.

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.

EPA guidance on assessment of negative symptoms in schizophrenia.

BACKGROUND: During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. METHODS: In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. RESULTS: Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. CONCLUSIONS: The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

Baseline measures of cerebral glutamate and GABA levels in individuals at ultrahigh risk for psychosis: Implications for clinical outcome after 12 months.

BACKGROUND: Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up. METHODS: About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = -0.34, N = 51, p = 0.01) in an explorative analysis. CONCLUSIONS: The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

High suicide rates during psychiatric inpatient stay and shortly after discharge.

OBJECTIVE: Over recent decades, intense efforts to address suicides in psychiatric admitted people have been initiated. The aim was to calculate suicide rates, rate ratios, population attributable risks (PAR) and trends among people admitted to or recently discharged from psychiatric wards. METHODS: Using a cohort design, we obtained nationwide register data on 6 292 932 individuals aged 15+ living in Denmark during 1995-2016. Of these, 178 703 (5.73%) males and 201 033 females (6.33%) had been admitted to psychiatric hospital. Incidence rate ratios (IRR) were obtained using Poisson regression analyses while adjusting for age and calendar period. Trends were assessed using joinpoint analyses. RESULTS: In total, 15 075 persons died by suicide, of which 6174 had been psychiatrically admitted. Among males, the suicide rate during the first week of admission and after discharge was 3409 and 3148 per 100 000 person-years, respectively. The corresponding values for females were 1267 and 1631. Generally, estimated suicide rates were highest in those with affective or anxiety stress disorders. During first week of hospitalization, the IRR was 237 for males and of 322 for females when compared with those never hospitalized. In first week after discharge, the IRR was 225 and 425 for males and females, respectively. PAR estimates indicated 6% of male suicides and 13% of female suicides attributes to first week of admission and discharge. The inpatient suicide rate decreased annually 2.5% until 2009 followed by a 7.5% annual percentage increase. The suicide rate after discharge decreased steadily annually over the study period. CONCLUSION: Despite finding declining post-discharge suicide rates, the period surrounding a psychiatric admission was still associated with extremely high suicide rates.

Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

Basic symptoms influence real-life functioning and symptoms in individuals at high risk for psychosis.

OBJECTIVE: To investigate potential clinical differences in high-risk profiles presenting with and without basic symptoms, and additionally investigate the association between basic symptoms and clinical symptoms, functioning, and cognition. METHODS: High-risk individuals (n = 133) were stratified into individuals fulfilling ultra-high-risk (UHR) criteria (n = 59) and individuals fulfilling UHR+ basic symptoms criteria (BS) (n = 74). Group differences were assessed on clinical symptoms, real-life functioning, and cognition. Regression analyses were conducted to elucidate on the relationship between BS and clinical symptoms, functioning, neurocognition, and social cognition. RESULTS: The group fulfilling both UHR+ BS criteria had significantly more symptoms and lower real-life functioning and quality of life but not more cognitive deficits. BS influenced on attenuated psychotic, depressive, and general symptoms, but only modestly on negative symptoms. No relationship between BS and neuro- and social cognition was established except for an association with emotion recognition processing speed. BS influenced real-life functioning, and this finding was sustained when controlling for the effect of negative symptoms. CONCLUSIONS: Our findings indicate that BS contribute highly to the distress and symptom load of clinical high-risk individuals. Longitudinal findings are needed to establish the predictive validity of BS on high-risk individuals' clinical and functional prognosis.

Risk of homelessness after discharge from psychiatric wards in Denmark: a nationwide register-based cohort study.

OBJECTIVE: To examine the absolute and relative risk of homelessness following discharge from psychiatric wards in Denmark. METHODS: A nationwide, register-based, cohort study including people aged 18+ years discharged from psychiatric wards in Denmark between 1 January 2001 and 31 December 2015. We analysed associations between psychiatric diagnoses and risk of homelessness using survival analysis. RESULTS: A total of 126 848 psychiatric in-patients were included accounting for 94 835 person-years. The incidence of homelessness one year following discharge was 28.18 (95% CI 26.69-29.75) and 9.27 (95% CI 8.45-10.16) per 1000 person-years at risk in men and women respectively. The one-year cumulative probability of first homelessness after discharge from psychiatric wards was 1.58% (95% CI 1.48-1.68) in males and 0.55% (95% CI 0.50-0.61) in females. Substance use disorders increased the risk of homelessness after discharge with adjusted incidence rate ratios of 6.60 (95% CI 5.19-8.40) (men) and 13.06 (95% CI 9.31-18.33) (women), compared with depressive disorders. Prior history of homelessness was an important predictor for homelessness following discharge. CONCLUSIONS: The first year following discharge from psychiatric wards is a high-risk period of homelessness, especially when having a substance use disorder or a prior history of homeless shelter contact. Improved efforts to prevent homelessness are needed.

Schizophrenia and attendance in primary healthcare: a population-based matched cohort study.

Objective: Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. The general practitioner (GP) plays a key role in the treatment of mental and physical multimorbidity. Nevertheless, it is unclear how much individuals with schizophrenia use primary healthcare. This study aims to investigate the yearly numbers of consultations in general practice for individuals with schizophrenia. Design and Setting: We performed a population-based matched cohort study of 21,757 individuals with schizophrenia and 435,140 age- and gender-matched references from Danish National Registers. Monthly general practice consultations were analysed using a generalized linear model with log link and assuming negative binomial distribution. Main outcome measures: Consultation rates in general practice up to17 years after index diagnosis. Results: Individuals with schizophrenia attended their GP more than references throughout the study period. The cases had 82% (95% CI: 78-87) and 76% (95% CI: 71-80) more consultations in primary care after 1 year and 5 years, respectively. Individuals with both schizophrenia and comorbid somatic illness attended even more. Conclusion: Individuals with schizophrenia are in regular contact with their GP, especially if they have comorbid illnesses. Whether an average of six consultations per year for individuals with schizophrenia is sufficient is up for debate. The study demonstrates a potential for an increased prevention and treatment of individuals with schizophrenia in general practice. KEY POINTS Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. Little is known about the attendance pattern in primary care for individuals with schizophrenia. •We found high attendance rates in primary care for individuals diagnosed with schizophrenia from index diagnosis and at least 17 years after diagnosis, which suggests opportunities for earlier intervention to improve their somatic health. •We found an association between high illness comorbidity and increased risk of not attending the general practitioner. The most severely somatically and mentally ill individuals may thus be difficult to reach and support in the current healthcare system.

Home visits in the Danish High Risk and Resilience Study - VIA 7: assessment of the home environment of 508 7-year-old children born to parents diagnosed with schizophrenia or bipolar disorder.

OBJECTIVE: The home environment provided by the caregivers of a child is an influential single factor for development and well-being. We aimed to compare the quality of the home environment of children at familial high risk of schizophrenia or bipolar disorder with population-based controls. METHODS: Danish nationwide registers were used to retrieve a cohort of 522 7-year-old children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) or none of these diagnoses (N = 200). The home environment was assessed using the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory). RESULTS: The proportion of children living in home environments that were evaluated not to meet the needs of a 7-year-old child was significantly larger in the two familial high-risk groups. This was true for 21% of the children with familial predisposition for schizophrenia and 7% of children with familial disposition for bipolar disorder. CONCLUSION: Children born to parents diagnosed with schizophrenia and to a lesser extent bipolar disorder are at an increased risk of growing up in a home environment with an insufficient level of stimulation and support. Identifying families with inadequate home environments is a necessary step towards specialized help and support to at-risk families.

Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials.

BACKGROUND: No study has gathered evidence from all randomized clinical trials (RCTs) with anti-inflammatory drugs measuring antidepressant effects including a detailed assessment of side-effects and bias. METHODS: We performed a systematic review identifying RCTs published prior to January 1, 2018, studying antidepressant treatment effects and side-effects of pharmacological anti-inflammatory intervention in adults with major depressive disorder (MDD) or depressive symptoms. Outcomes were depression scores after treatment, remission, response, and side-effects. Pooled standard mean differences (SMD) and risk ratios (RR) including 95% confidence intervals (95%-CI) were calculated. RESULTS: We identified 36 RCTs, whereof 13 investigated NSAIDs (N = 4214), 9 cytokine inhibitors (N = 3345), seven statins (N = 1576), 3 minocycline (N = 151), 2 pioglitazone (N = 77), and 2 glucocorticoids (N = 59). Anti-inflammatory agents improved depressive symptoms compared to placebo as add-on in patients with MDD (SMD = -0.64; 95%-CI = -0.88, -0.40; I2  = 51%; N = 597) and as monotherapy (SMD = -0.41; 95%-CI = -0.60, -0.22; I2  = 93%, N = 8825). Anti-inflammatory add-on improved response (RR = 1.76; 95%-CI = 1.44-2.16; I2  = 16%; N = 341) and remission (RR = 2.14; 95%-CI = 1.03-4.48; I2  = 57%; N = 270). We found a trend toward an increased risk for infections, and all studies showed high risk of bias. CONCLUSION: Anti-inflammatory agents improved antidepressant treatment effects. Future RCTs need to include longer follow-up, identify optimal doses and subgroups of patients that can benefit from anti-inflammatory intervention.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders-medium-term follow-up and clinical course.

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.

Impact of severe mental illness on cancer stage at diagnosis and subsequent mortality: A population-based register study.

BACKGROUND: Excess mortality in individuals with severe mental illness (SMI) is often explained by physical comorbidity and suboptimal healthcare. Cancer is a prevalent cause of death, and tumour stage at diagnosis is a strong predictor of mortality. We aimed to study cancer incidence, disease stage at diagnosis and subsequent mortality in individuals with SMI compared to individuals without SMI. METHODS: The entire Danish population was followed in 1978-2013 using nationwide registries. Cancer incidence and subsequent mortality stratified by disease stage were compared in individuals with and without SMI. Cox regression was used to estimate incidence rate ratios (IRR) and mortality rate ratios (MRR). Cancer was examined overall and grouped by major aetiological factors. RESULTS: The overall cancer incidence rate was lower in males with SMI than in males without SMI; IRR = 0.89 (95% CI: 0.85-0.94), but rates were similar in females with SMI and without SMI; IRR = 1.03 (95% CI: 0.99-1.07). The overall mortality rate was higher in individuals with SMI than those without; MRR = 1.56 (95% CI: 1.48-1.64) for males and MRR = 1.49 (95% CI: 1.43-1.56) for females. Incidence rates and mortality rates showed similar estimates when stratified by tumour stage and aetiology. CONCLUSIONS: We found lower cancer incidence in males with SMI compared to males without SMI and similar incidence in the two groups of women. Higher subsequent mortality was found in both sexes with SMI. The excess mortality was not explained by more advanced stages of cancer; future studies should evaluate the effect of cancer treatment and rehabilitation.

Patient-controlled hospital admission for patients with severe mental disorders: a nationwide prospective multicentre study.

OBJECTIVE: To assess whether implementing patient-controlled admission (PCA) can reduce coercion and improve other clinical outcomes for psychiatric in-patients. METHODS: During 2013-2016, 422 patients in the PCA group were propensity score matched 1:5 with a control group (n = 2110) that received treatment as usual (TAU). Patients were followed up for at least one year using the intention to treat principle utilising nationwide registers. In a paired design, the outcomes of PCA patients during the year after signing a contract were compared with the year before. RESULTS: No reduction in coercion (risk difference = 0.001; 95% CI: -0.038; 0.040) or self-harming behaviour (risk difference = 0.005; 95% CI: -0.008; 0.018) was observed in the PCA group compared with the TAU group. The PCA group had more in-patient bed days (mean difference = 28.4; 95% CI: 21.3; 35.5) and more medication use (P < 0.0001) than the TAU group. Before and after analyses showed reduction in coercion (P = 0.0001) and in-patient bed days (P = 0.0003). CONCLUSION: Implementing PCA did not reduce coercion, service use or self-harm behaviour when compared with TAU. Beneficial effects of PCA were observed only in the before and after PCA comparisons. Further research should investigate whether PCA affects other outcomes to better establish its clinical value.

The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders.

The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.

Fever and infections during pregnancy and psychosis-like experiences in the offspring at age 11. A prospective study within the Danish National Birth Cohort.

BACKGROUND: Maternal exposures to fever and infections in pregnancy have been linked to subsequent psychiatric morbidity in the child. This study examined whether fever and common infections in pregnancy were associated with psychosis-like experiences (PLEs) in the child. METHODS: A longitudinal study of 46 184 children who participated in the 11-year follow-up of the Danish National Birth Cohort was conducted. Pregnant women were enrolled between 1996 and 2002 and information on fever, genitourinary infections, respiratory tract infection, and influenza-like illness during pregnancy was prospectively collected in two interviews during pregnancy. PLEs were assessed using the seven-item Adolescent Psychotic-Like Symptom Screener in a web-based questionnaire completed by the children themselves at age 11. RESULTS: PLEs were reported among 11% of the children. Multinomial logistic regression models with probability weights to adjust for potential selection bias due to attrition suggested that maternal fever, genitourinary infections and influenza-like illness were associated with a weak to moderate increased risk of subclinical psychosis-like symptoms in the offspring, whereas respiratory tract infections were not. No clear pattern was observed between the strengths of the associations and the timing of exposure, or the type of psychosis-like symptom. CONCLUSIONS: In this study, maternal exposures to fevers and common infections in pregnancy were generally associated with a subtle excess risk of PLEs in the child. A more pronounced association was found for influenza-like illness under an a priori definition, leaving open the possibility that certain kinds of infections may constitute important risk factors.