Help-Seeking Undocumented Migrants in the Netherlands: Mental Health, Adverse Life Events, and Living Conditions.

Undocumented migrants are a particularly vulnerable group regarding (mental) health, living conditions, and restricted access to health care. The aim and objective of the study was to examine the prevalence and correlates of mental health problems in a help-seeking population of undocumented migrants. Observational study was performed by integrating cross-sectional questionnaire data with retrospective electronic patient record data. Undocumented migrants attending medical and psychological consultation hours of a Netherlands-based non-governmental organization completed the Self-Reporting Questionnaire (SRQ). We examined scores of the instrument's 24 items version (SRQ-24) and its 20 items version (SRQ-20). Correlates of mental health were estimated using parametric tests. On the SRQ-20, 85% (95% CI 77-91%) of the sample (N = 101) scored ≥ 8, the clinical cut-off value for common mental disorders; mean = 12.4 ± 4.6, range 0-20. Adverse life events like physical and sexual assault were reported in 37% of the medical records (N = 99) and had a medium-to-large effect (Cohen's d = 0.76) on SRQ-24 scores. Mental health problems are common in help-seeking undocumented migrants. This study underlines the need of improving access to mental health care for undocumented migrants.

Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study.

BACKGROUND: There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder. AIMS: We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder. METHOD: We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses. RESULTS: Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28-1.66, P = 1.44 × 10-8, lifetime smoking ORIVW = 1.72, 95% CI 1.29-2.28, P = 1.8 × 10-4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003-0.053, P = 2.9 × 10-2). CONCLUSIONS: These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis.

BACKGROUND: Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. METHODS: In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes ('normal', 'mixed' and 'impaired') in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. RESULTS: Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. CONCLUSIONS: Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Measuring process indicators and adverse events to assess the quality of care for inpatients with psychosis.

BACKGROUND: Research into the quality of care in psychiatry is scarce. Data collection is falling behind that for other fields of medicine and therefore the opportunity to improve care is missed. AIMS: In this medical record study we aim to determine: (i) whether or not patients' physical health indicators are assessed and pharmacological and behavioural treatment interventions applied; (ii) the incidence and nature of adverse events in psychotic inpatients. METHODS: Medical records of inpatients with psychosis admitted to psychiatric wards at Amsterdam UMC, location AMC, Department of psychiatry, were screened with a previously developed and tested two-step patient safety tool. RESULTS: Data of 299 admissions were included. Physical health indicators were not assessed in one-third of cases. Fifty-five percent of the patients were smokers but only 1% received an intervention. The family was actively involved in 43% of the cases. During 11,403 admission days, 235 adverse events had been recorded. The most frequent adverse event was adverse drug reactions (40%), which were mostly related to antipsychotic medication. CONCLUSIONS: In conclusion, quality of care auditing is useful to prioritize areas that need improvement. Future research should focus on interventions to improve the quality of psychiatric care.

The co-occurrence of smoking and suicide.

This article is an invited commentary on a recent article by Harrison et al. investigating the purported causal link between smoking behaviours and suicide attempts.

Short-term sequences of aggressive behavior in psychiatric inpatients with psychotic disorders using Markov models.

BACKGROUND: Aggression in inpatients with psychotic disorders is harmful to patients and health care professionals. AIMS: The current study introduces a novel approach for assessing short-term sequences of different types of aggression. METHODS: Occurrence and type of aggressive behavior was assessed retrospectively by reviewing hospital charts in a sample of 120 inpatients with psychotic disorders, admitted to the psychiatric wards of an academic hospital using the Modified Overt Aggression Scale (MOAS). Behavioral sequences of verbal aggression, physical aggression against objects, physical aggression against oneself and physical aggression against others were analyzed by using Markov models, a statistical technique providing the probabilities of transferring from one state to another. RESULTS: The Markov models showed that when patients behave aggressively, they are likely to either show the same type of aggression or to be non-aggressive consecutively. Patients are, however, unlikely to subsequently show another type of aggression. Non-aggressive behavior is very unlikely to result in physical aggression or aggression against objects. CONCLUSION: The current study introduced a novel approach on how to investigate aggressive behavior in patients with psychotic disorders. Replication of our results in a bigger sample is needed to reliably develop a day-to-day risk assessment tool for aggressive behavior.

Comparing Rates of Adverse Events and Medical Errors on Inpatient Psychiatric Units at Veterans Health Administration and Community-based General Hospitals.

OBJECTIVE: There is limited knowledge about how general hospitals and Veterans Health Administration (VHA) hospitals fare relative to each other on a broad range of inpatient psychiatry-specific patient safety outcomes.This research compares data from 2 large-scale epidemiological studies of adverse events (AEs) and medical errors (MEs) in inpatient psychiatric units, one in VHA hospitals and the other in community-based general hospitals. METHOD: Retrospective medical record reviews assessed the prevalence of AEs and MEs in a sample of 4371 discharges from 14 community-based general hospitals (derived from 69,081 discharges at 85 hospitals) and a sample of 8005 discharges from 40 VHA hospitals (derived from 92,103 discharges at 105 medical centers). Rates of AEs and MEs across hospital systems were calculated, controlling for relevant patient and hospital characteristics. RESULTS: The overall rate of AEs and MEs in inpatient psychiatric units of VHA hospitals was 7.11 and 1.49 per 100 patient discharges; at community-based acute care hospitals, these rates were 13.48 and 3.01 per 100 patient discharges. The adjusted odds ratio of a patient experiencing an AE and a ME at community-based hospitals as compared with VHA hospitals was 2.11 and 2.08, respectively. CONCLUSION: Although chart reviews may not document the complete nature and outcomes of care, even after controlling for differences in patient and hospital characteristics, psychiatric inpatients at community-based hospitals were twice as likely to experience AEs or MEs as inpatients at VHA hospitals. While community-based hospitals may lag behind VHA hospitals, both hospital systems should continue to pursue evidence-based improvements in patient safety. Future research aimed at changing hospital practices should draw on established strategies for bridging the gap from research to practice in order to improve the quality of care for this vulnerable patient population.

"But I did not touch nobody!"-Patients' and nurses' perspectives and recommendations after aggression on psychiatric wards-A qualitative study.

AIMS: To gain a deeper understanding of the differences in patients and staff perspectives in response to aggression and to explore recommendations on prevention. DESIGN: Qualitative, grounded theory study. METHODS: We conducted semi-structured interviews with patients and nurses involved in an aggressive incident. Data collection was performed from May 2016 - March 2017. RESULTS: Thirty-one interviews were conducted concerning 15 aggressive incidents. Patients and nurses generally showed agreement on the factual course of events, there was variation in agreement on the perceived severity (PS). Patients' recommendations on prevention were mostly personally focussed, while nurses suggested general improvements. CONCLUSION: Patients are often capable to evaluate aggression and give recommendations on prevention shortly after the incident. Patients and nurses differ in the PS of aggression. Recommendations on prevention of patients and nurses are complementary. IMPACT: What problem did the study address? Perspectives of patients and nurses differ with respect to aggression, but how is unclear. What were the main findings? Patients and nurses generally described a similar factual course of events concerning the incident, patients often perceive the severity less than nurses. Patients are capable to give recommendations on prevention of aggressive incidents, shortly after the incident. Where and on whom will the research have impact? Factual course of events can be a common ground to start evaluating aggressive incidents and post-incident review should address the severity of incidents. Asking recommendations from patients on how to improve safety and de-escalation can lead to innovative and personal de-escalation strategies and supports patients autonomy.

Patient safety in South Africa: PICU adverse event registration*.

OBJECTIVE: Adverse event registration is a means to improve patient safety in a PICU. So far it has been used in European and North American countries mainly. We studied adverse events in a South African setting with the aims to 1) assess rates and types of adverse events with two different registration methods and 2) describe characteristics of patients experiencing adverse events. DESIGN: This study consisted of 1) a retrospective audit of randomly selected patient records and 2) a prospective observational study of real-time registration of AEs during ward rounds. Adverse events were identified using the Child Health Corporation of America - Pediatric Pharmacy Advocacy Group PICU trigger tool. SETTING: A multidisciplinary 20 bed PICU at the Red Cross War Memorial Children's Hospital in Cape Town. PATIENTS: The retrospective section of the study involved 80 randomly selected patients who had been discharged from the PICU, and the prospective study involved patients who were present in the PICU between March and June 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The retrospective audit identified 260 adverse events in 61 patients (50.8 per 100 patient days). Nineteen patients (24%) did not have any adverse events. Catheter complications, hypoglycemia, and endotracheal tube malpositioning requiring repositioning were most frequent. Prospective registration during 58 ward rounds revealed 272 adverse events in 236 patients (27.2 per 100 patient days), particularly catheter complications, nosocomial infection, and surgical complications. Hundred thirty-two patients of the total 236 patients (56%) did not experience an adverse event. Patients experiencing adverse events underwent mechanical ventilation significantly more frequently. Length of stay was significantly associated with number of adverse events. CONCLUSIONS: The trigger tool method identifies a higher adverse event rate compared with real-time registration. Each method has a unique contribution to yield types of adverse events.

Long-term Changes in Personal Recovery and Quality of Life Among Patients With Schizophrenia Spectrum Disorders and Different Durations of Illness: A Meta-analysis.

BACKGROUND AND HYPOTHESIS: In schizophrenia spectrum disorders (SSD) personal recovery and subjective quality of life (S-QOL) are crucial and show conceptual overlap. There is limited knowledge about how these outcomes change over time. Therefore, we investigated changes in personal recovery or S-QOL for patients with SSD. We specifically focused on the influence of the patients' durations of illness (DOI) on changes in personal recovery and S-QOL. STUDY DESIGN: We included 46 studies investigating longitudinal changes in quantitative assessments of personal recovery or S-QOL for patients with SSD. Outcomes were categorized in overall personal recovery, overall S-QOL connectedness, hope and optimism, identity, meaning in life, and empowerment. We evaluated effect sizes of change between baseline and follow-up assessments. We also evaluated potential moderating effects, including DOI on these changes in outcomes. STUDY RESULTS: We found small improvements of overall personal recovery and S-QOL, but marginal or no improvement over time in the other more specific outcome domains. Patients without a schizophrenia diagnosis, a younger age, and more recent publications positively influenced these changes. We found no significant influence of DOI on the changes in any outcome domain. CONCLUSIONS: Improvement in personal recovery or S-QOL of people with SSD is modest at best. However, these studies did not fully capture the personal narratives or nonlinear process of recovery of an individual. Future research should focus on how to shift from a clinical to more person-oriented approach in clinical practice to support patients in improving their personal process of recovery. REVIEW PROTOCOL REGISTRATION: CRD42022377100.

A genetic exploration of the relationship between Posttraumatic Stress Disorder and cardiovascular diseases.

Background and Aims: Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD. Methods: We leveraged summary-level data of genome-wide association studies (PTSD: N= 1,222,882; atrial fibrillation (AF): N=482,409; coronary artery disease (CAD): N=1,165,690; hypertension: N=458,554; heart failure (HF): N=977,323). First, we estimated genetic correlations and utilized genomic structural equation modeling to identify a common genetic factor for PTSD and CVD. Next, we assessed biological, behavioural, and psychosocial factors as potential mediators. Finally, we employed multivariable Mendelian randomization to examine causal pathways between PTSD and CVD, incorporating the same potential mediators. Results: Significant genetic correlations were found between PTSD and CAD, HT, and HF (rg =0.21-0.32, p≤ 3.08 · 10-16), but not between PTSD and AF. Insomnia, smoking, alcohol dependence, waist-to-hip ratio, and inflammation (IL6, C-reactive protein) partly mediated these associations. Mendelian randomization indicated that PTSD causally increases CAD (IVW OR=1.53, 95% CIs=1.19-1.96, p=0.001), HF (OR=1.44, CIs=1.08-1.92, p=0.012), and to a lesser degree hypertension (OR=1.25, CIs=1.05-1.49, p=0.012). While insomnia, smoking, alcohol, and inflammation were important mediators, independent causal effects also remained. Conclusions: In addition to shared genetic liability between PTSD and CVD, we present strong evidence for causal effects of PTSD on CVD. Crucially, we implicate specific lifestyle and biological mediators (insomnia, substance use, inflammation) which has important implications for interventions to prevent CVD in PTSD patients.

Risk Factors for Psychotic Relapse After Dose Reduction or Discontinuation of Antipsychotics in Patients With Chronic Schizophrenia. A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND HYPOTHESIS: Although maintenance treatment with antipsychotics protects against psychotic relapse, high doses may hamper recovery. Therefore, dose reduction or discontinuation may be considered in patients with chronic schizophrenia. Here, we identified risk factors for psychotic relapse when doses are reduced. STUDY DESIGN: We systematically searched MEDLINE, EMBASE, and PsycINFO from January 1950 through January 2021 and reviewed randomized controlled trials (RCTs) that reported relapse rates after antipsychotic dose reduction or discontinuation in patients with chronic schizophrenia. We calculated relative risks (RRs) with 95% confidence intervals (CIs) per person-year and sought to identify potential risk factors for relapse. The study is registered with PROSPERO (CRD42017058296). STUDY RESULTS: Forty-seven RCTs (54 patient cohorts, 1746 person-years) were included. The RR for psychotic relapse with dose reduction/discontinuation versus maintenance treatment was 2.3 per person-year (95% CI: 1.9 to 2.8). The RR was higher with antipsychotic discontinuation, dose reduction to less than 3-5 mg haloperidol equivalent (HE), or relatively rapid dose reduction (<10 weeks). The RR was lower with long-acting injectable agents versus oral antipsychotic dose reduction. Other factors that increased the risk of psychotic relapse were younger age and short follow-up time. CONCLUSIONS: Clinicians should take several risk factors for psychotic relapse into account when considering dose reduction in patients with chronic schizophrenia. Studies of a relatively fast reduction in antipsychotic dose support a minimum dose of 3-5 mg HE. However, if the dose is tapered more gradually, relapses related to medication withdrawal might be avoided, possibly enabling lower-end doses to be achieved.

Short- and long-term changes in symptom dimensions among patients with schizophrenia spectrum disorders and different durations of illness: A meta-analysis.

In schizophrenia spectrum disorders, improvement in symptoms varies between patients with short and long durations of illness. In this meta-analysis we provided an overview of both short- and long-term symptomatic improvement for patients with schizophrenia spectrum disorders with distinct durations of illness. We included 82 longitudinal studies assessing the course of positive, negative, depressive and disorganization symptoms. We analyzed effect sizes of change in four subgroups based on durations of illness at baseline: <2 years, 2-5 years, 5-10 years, >10 years. Potential moderators were explored using meta-regression and sensitivity analyses. Overall, we found large improvements of positive symptoms and small improvements of negative, depressive, and disorganization symptoms. Positive and disorganization symptoms improved relatively stronger for patients earlier in the course of illness, whereas negative and depressive symptoms showed modest improvement regardless of duration of illness. Improvement of symptoms was associated with higher baseline severity of positive symptoms, a younger age, a smaller subsample with schizophrenia, and, specifically for negative symptoms, higher baseline severity of depressive symptoms. Future research should focus on exploring ways to optimize improvement in negative and depressive symptoms for patients with schizophrenia spectrum disorders.

Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls.

It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSs-smoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms.

Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: an in-depth genetic exploration of population samples.

Background: An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. While arrhythmic disorders play an important role in this, the nature of the relation between schizophrenia and arrhythmia is not fully understood. Methods: We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53,386 cases 77,258 controls), arrhythmic disorders (atrial fibrillation, 55,114 cases 482,295 controls; Brugada syndrome, 2,820 cases 10,001 controls) and electrocardiogram traits (heart rate (variability), PR interval, QT interval, JT interval, and QRS duration, n=46,952-293,051). First, we examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Next, we explored bidirectional causal relations between schizophrenia and arrhythmic disorders and electrocardiogram traits using Mendelian randomization. Outcomes: There was no evidence for global genetic correlations, except between schizophrenia and Brugada (rg=0·14, p=4·0E-04). In contrast, strong positive and negative local genetic correlations between schizophrenia and all cardiac traits were found across the genome. In the strongest associated regions, genes related to immune system and viral response mechanisms were overrepresented. Mendelian randomization indicated a causal, increasing effect of liability to schizophrenia on Brugada syndrome (OR=1·15, p=0·009) and heart rate during activity (beta=0·25, p=0·015). Interpretation: While there was little evidence for global genetic correlations, specific genomic regions and biological pathways important for both schizophrenia and arrhythmic disorders and electrocardiogram traits emerged. The putative causal effect of liability to schizophrenia on Brugada warrants increased cardiac monitoring and potentially early medical intervention in patients with schizophrenia. Funding: European Research Council Starting Grant.

Impact of a smoke-free policy on smoking prevalence on hospital grounds: A before-after study.

INTRODUCTION: Studies on the impact of smoke-free policies (SFPs) on hospitals grounds on on-site smoking are scarce. On 1 October 2019, an SFP was implemented on the grounds of the Amsterdam UMC hospital in the Netherlands, including measures for sustained enforcement. This study assessed the impact of this SFP on smoking prevalence on hospital grounds up to 18 months after implementation. METHODS: Observations were systematically conducted 7 weeks before and after the SFP was implemented, and at 5 and 18 months afterwards. A total of 32 sites were included in the study, divided over two hospital locations. On each site, the number of smokers was systematically observed and categorized into staff, patient, student, or visitor. Smoking prevalence on hospital grounds was calculated by the number of observed smokers as a proportion of all people observed. Bubble maps were created to visualize changes in the geographical distribution of smokers. RESULTS: Smoking prevalence on hospital grounds decreased significantly from 17.4% before to 3.3% after implementation of the SFP. Following implementation, the largest decrease was observed in smoking among staff (-96.7%) and patients (-92.3%). The decrease in smoking prevalence was sustained 18 months after implementation (5.0%). The number of smokers decreased on nearly all sites. CONCLUSIONS: The substantial and sustained decrease in smoking prevalence found in this study highlights the potential of SFPs on hospital grounds to protect people from exposure to (secondhand) smoking. Continued enforcement of these SFPs seems essential to ensure ongoing compliance.

Changes in social functioning over the course of psychotic disorders-A meta-analysis.

In this meta-analysis we investigated changes in social functioning and its moderators in patients with a psychotic disorder but different durations of illness at baseline. We included longitudinal studies assessing the course of five domains of social functioning in patients with a psychotic disorder. Effect sizes of change between baseline and follow-up within these domains were analyzed in four subgroups based on durations of psychotic disorder at baseline: less than 2 years, between 2 and 5 years, between 5 and 10 years, and more than 10 years. The influence of baseline confounders was analyzed using meta-regression and sensitivity analysis. We included 84 studies analyzing 33,456 participants. We found a medium improvement (d = 0.60) in overall social functioning over time, with a greater improvement for studies investigating patients with a duration of illness of less than 5 years. We found minor improvement in specific domains of social functioning, such as vocational functioning (d = 0.31), prosocial behavior (d = 0.36), activities (d = 0.15), and independence (d = 0.25). Improvement in social functioning was associated with lower baseline levels of negative symptoms, higher baseline levels of quality of life, and, specifically, improved vocational functioning, with rehabilitation and combined treatment. Social functioning in patients with psychotic disorders improves over time, especially for patients with shorter illness durations. Reduction of negative symptoms and improving quality of life might reinforce improvement of social functioning.

Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study.

Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (-0.02-0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis.

Differential trajectories of tobacco smoking in people at ultra-high risk for psychosis: Associations with clinical outcomes.

Objective: People at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown. Methods: We investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS. Results: We identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = -10.40, SE = 3.41, p = 0.003; ES = -22.36, SE = 10.07, p = 0.027), Increasing (ES = -11.35, SE = 4.55, p = 0.014; ES = -25.58, SE = 13.17, p = 0.050) and Low (ES = -11.38, SE = 3.29, p = 0.001; ES = -27.55, SE = 9.78, p = 0.005) classes, respectively. Conclusions: These findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on the potential of modifying smoking behavior and its relation to clinical outcomes.