Beyond Housing: Supporting the Health and Well-Being of Individuals Residing in Toronto's Temporary Shelter Hotels.

In response to the COVID-19 pandemic, the City of Toronto opened temporary shelter hotels with on-site supports for people previously living on the street, in encampments or in emergency shelters. The Beyond Housing program was created to enhance service offerings in the shelter hotel system and to support people not engaging with services. Using a Housing First approach, Beyond Housing offers three main interventions: (1) case management, (2) care coordination and (3) on-site and community-based mental health and social supports. This commentary explores the strengths and challenges of implementing Beyond Housing within temporary shelter hotels, and then discusses the lessons learned.

Navigator programme for hospitalised adults experiencing homelessness: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: People experiencing homelessness suffer from poor outcomes after hospitalisation due to systemic barriers to care, suboptimal transitions of care, and intersecting health and social burdens. Case management programmes have been shown to improve housing stability, but their effects on broad posthospital outcomes in this population have not been rigorously evaluated. The Navigator Programme is a Critical Time Intervention case management programme that was developed to help homeless patients with their postdischarge needs and to link them with community-based health and social services. This randomised controlled trial examines the impact of the Navigator Programme on posthospital outcomes among adults experiencing homelessness. METHODS AND ANALYSIS: This is a pragmatic randomised controlled trial testing the effectiveness of the Navigator Programme at an urban academic teaching hospital and an urban community teaching hospital in Toronto, Canada. Six hundred and forty adults experiencing homelessness who are admitted to the hospital will be randomised to receive support from a Homeless Outreach Counsellor for 90 days after hospital discharge or to usual care. The primary outcome is follow-up with a primary care provider (physician or nurse practitioner) within 14 days of hospital discharge. Secondary outcomes include postdischarge mortality or readmission, number of days in hospital, number of emergency department visits, self-reported care transition quality, and difficulties meeting subsistence needs. Quantitative outcomes are being collected over a 180-day period through linked patient-reported and administrative health data. A parallel mixed-methods process evaluation will be conducted to explore intervention context, implementation and mechanisms of impact. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Unity Health Toronto Research Ethics Board. Participants will be required to provide written informed consent. Results of the main trial and process evaluation will be reported in peer-reviewed journals and shared with hospital leadership, community partners and policy makers. TRIAL REGISTRATION NUMBER: NCT04961762.

Epigenetic studies in suicidal ideation and behavior.

Most psychiatric disorders are associated with an elevated risk of suicide. Suicidal behavior is the product of the interaction of many risk factors, such as genetics and environmental factors. Hence, epigenetics research may help to understand the mechanisms leading to suicidal ideation and behavior. This review will discuss epigenetic studies in both suicidal ideation and behavior. Epigenetic modifications are likely to be important in both suicidal ideation and behavior. Most of the reviewed studies found significant epigenetic modifications linked with suicidal behavior rather than ideation. Although sizable research has been carried out on this topic, most studies have been done on small-scale samples, and future research is required in larger samples with better clinical characterization of suicide phenotypes to investigate these epigenetic modifications further.

Epigenetics of Schizophrenia.

Schizophrenia (SCZ) is a chronic psychotic disorder that contributes significantly to disability, affecting behavior, thought, and cognition. It has long been known that there is a heritable component to schizophrenia; studies in both the pre-genomic and post-genomic era, however, have failed to elucidate fully the genetic basis for this complex disease. Epigenetic processes - broadly, those which contribute to changes in gene expression without altering the genetic code itself - may help to understand better the mechanisms leading to development of SCZ. The objective of this review is to synthesize current knowledge of the epigenetic mechanisms involved in schizophrenia. Specifically, DNA methylation studies in both peripheral and post-mortem brain samples in SCZ are reviewed, as are epigenetic mechanisms including histone modification. The promising role of non-coding RNA including micro-RNA (miRNA) and its role as a potential diagnostic and therapeutic biomarker is outlined, as are epigenetic age acceleration and telomere shortening. Finally, we discuss limitations in current knowledge and propose future research directions.

Mediating effect of genome-wide DNA methylation on suicidal ideation induced by perceived stress.

Stress is an important risk factor for suicidal ideation, but the mechanisms that link stress, suicidal ideation and neurobiology remain unclear. Epigenetic mechanisms are involved in both vulnerability to suicidal behavior and stress. This is a pilot study of 60 patients with schizophrenia spectrum disorders (36 men and 24 women), with an average age of 43.75 ± 12.24 years. We analyzed the effects of (1) perceived stress and (2) the mediation of genome-wide methylation (~450 000 CpG sites) on suicidal ideation severity. The top CpG site mediating the effect of stress on suicidal ideation was the cg10782349 located in the ZNF701 gene on chromosome 19, facilitating the effect through DNA hypermethylation. These preliminary results indicate that DNA methylation in peripheral tissues can clarify the complex relationship between stress and suicidal ideation in schizophrenia.

Biological aging in schizophrenia and psychosis severity: DNA methylation analysis.

The physiological changes associated with normal aging are known to occur earlier in individuals with schizophrenia (SCZ). One of the phenomena linked with normal aging is the change in patterns of epigenetic modifications. We recruited 138 individuals with SCZ spectrum disorders and extracted DNA from white blood cells. The combinations of pre-selected DNA methylation sites were utilized to estimate the 'methylation age' (DNAm age) and evaluate evidence of epigenetic age acceleration. We investigated the correlation between the epigenetic age acceleration measures and psychosis severity; furthermore, we estimated blood cell counts based on DNA methylation levels. The extrinsic epigenetic age acceleration showed a significant correlation with the Brief Psychiatric Rating Scale (BPRS) disorganization subscale(r=0.222, p=0.039).Both Horvath age acceleration and Hannum age acceleration showed a significant correlation (r=0.221, p=0.029; r=0.242, p=0.017 respectively) with the Symptom Checklist 90 (SCL-90) psychotic domain. Overall, this study shows some evidence of epigenetic age acceleration associated with psychosis severity using two different algorithms for DNAm age analysis.

Genome-wide methylation association with current suicidal ideation in schizophrenia.

In this study, we investigate the epigenetic mechanisms associated with current suicidal ideation. Gene expression changes have been found in post-mortem brain of suicide victims. However, it is not clear how in-vivo gene expression change confers risk for suicide. DNA methylation is a form of epigenetic modification that regulates gene expression. Our primary aim is to investigate genome-wide methylation in conferring risk for current suicidal ideation (SI) in schizophrenia. The presence of current SI and genome-wide methylation patterns were assessed in 107 patients with schizophrenia. DNA methylation has been measured in white blood cells as a possible peripheral biomarker of SI. SI was the primary outcome variable in a model including methylation status of white blood cells using the Illumina 450 array. We have tested the association with genome-wide methylation levels in 19 subjects with current SI and 88 subjects without current SI and we found that higher methylation level in the CpG cg06121808 located in the gene SLC20A1 on chromosome 2 was associated with current SI (p = 0.000003; beta difference = 0.06). Furthermore, the distal promoter analysis showed that the gene SMPD2 was hypermethylated in suicide ideators (p = 0.0001; beta difference = 0.02). Thus, molecular biomarkers could advance our understanding of the molecular mechanisms of stress-related SI. Furthermore, the methylation sites that we have identified should be replicated in other suicide related phenotypes to generate robust biomarkers with high translational value for proof of concept interventions aiming at reducing SI.

Genome-wide association study of aggression and violence in schizophrenia.

Schizophrenia patients are at higher risk of engaging in violent behavior than the general population. Schizophrenia is also regarded as a highly heritable disorder. This study aimed to analyze genome-wide the effect of SNPs on violence in schizophrenia. We recruited 205 subjects between the age of 18-75 from the Centre for Addiction and Mental Health (CAMH), who had a diagnosis of schizophrenia or schizoaffective disorder. We recorded physical, verbal and lifetime violence scores indicating any violent actions to inflict pain, bodily harm, or death on another individual from the standardized scale, Modified Overt Aggression Scale (MOAS). We genotyped each participant's DNA using the Illumina Omni 2.5, and the SNPs were analyzed using the whole genome analysis tool-set, PLINK. We probed for single nucleotide polymorphisms (SNPs) correlated with violence in schizophrenia patients. We found one SNP (rs2188177) on chromosome 7 which showed a trend for association with physical violence (p = 7.80E-06). This study is the first of its kind to investigate genome-wide, the polymorphisms associated with violence in schizophrenia. The findings of this study may promote collaborative efforts to understand the genetic basis of violent behavior in psychosis.

Early-life stressful events and suicide attempt in schizophrenia: Machine learning models.

Childhood abuse and neglect predicts suicide attempt. Furthermore, other early-life stressful events may predict lifetime suicide attempt in psychiatric disorders. We assessed 189 schizophrenics for suicide attempt and stressful life events. Early-life stressful events were used as predictors of lifetime suicide attempt in three machine learning models. In our sample, 38% of the schizophrenics had at least one suicide attempt lifetime. The machine learning models provided an overall significant prediction (accuracy range: 62-69%). Childhood sexual molestation and mental illness were important predictors of suicide attempt. Early-life stressful events should be included in models aiming at predicting suicide attempt in schizophrenia.

Meta-Analysis of Neuropsychological Studies in Panic Disorder Patients: Evidence of Impaired Performance during the Emotional Stroop Task.

BACKGROUND: Recent investigations have highlighted significant differences in verbal recall between patients with panic disorder (PD) and controls. These studies have highlighted that verbal memory and working memory could be impaired in PD. OBJECTIVES: The objective of the present meta-analysis is to confirm this hypothesis, reviewing the studies that have investigated neurocognitive testing in PD. METHODS: We performed a systematic literature search for studies published between 1980 and 2015 that reported cognitive measurements in PD patients and controls. Effect size estimates were computed using the restricted maximum likelihood model. Only case-control studies were selected for this meta-analysis. We included studies that made a direct comparison between PD subjects and healthy controls. The diagnostic group consisted of adult patients aged over 18 years diagnosed with PD. We excluded the studies that did not employ a case-control design. All statistical analyses were carried out on R using the "metafor" package version 1.9-8. The effect size for each study neuropsychological test was calculated using the mean and SD of performance results, and p values < 0.05 were considered significant. RESULTS: We identified few studies that tested verbal memory and executive functions in PD patients and controls, and this difference was not significant. On the other hand, there are several studies that have used the emotional Stroop task to assess cognitive functions in PD. There is no robust evidence of impairment of memory function in PD; however, when considering the emotional Stroop task, it was found that PD patients performed slower (p < 0.01) than healthy controls for all three types of stimuli (neutral, negative, positive). CONCLUSION: This meta-analysis included a small number of studies, which may have introduced bias into the analysis. However, there is some evidence of impairment of neurocognitive functions in PD when performing the emotional Stroop task. Furthermore, the paucity of studies evaluating neurocognition in PD suggests the need for further research in this field in order to draw meaningful conclusions.

Correlation Between Violence and Antipsychotic Dosage in Schizophrenia: A Secondary Analysis of The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) Dataset.

INTRODUCTION: Violent behavior is more common in individuals with schizophrenia, compared to the general population. Studies suggest higher psychotic symptoms are predictive of greater violent behavior. On the other hand, violent behaviors are reduced with antipsychotic treatment. However, the relationship between antipsychotic dosage and violence has not been studied to date. Thus, we aimed to determine if there exists an association between antipsychotic dosage and violence scores and whether the maximum violence would be predictive of the final antipsychotic dosage. We hypothesized that the violence scores at the final assessment in the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) would be correlated with the corresponding drug dosage and the maximum violence severity score would be predictive of the final dosage. METHODS: Antipsychotic dosage at the end of the trial was converted into defined daily dosage and chlorpromazine equivalents (CPZe). Final and maximum violence sum scores were analyzed from the final violence assessment interviews. Spearman's rank-order correlation and linear regression analyses were used to analyze the relationship between the violence scores and standardized antipsychotic dosages. RESULTS: The analysis was on 952 individuals with schizophrenia. There was a significant association between maximum violence severity score and the final CPZe dosage (p=0.049). Exploratory analysis of age and ethnicity revealed younger non-white individuals to be at a higher risk of engaging in violent activities. DISCUSSION: Violence in schizophrenia is associated with poor illness course. Further studies focusing on violence in younger non-white individuals are warranted.

The effect of ethnicity and immigration on treatment resistance in schizophrenia.

BACKGROUND: Treatment resistance is a common issue among schizophrenia patients undergoing antipsychotic treatment. According to the American Psychiatric Association (APA) guidelines, treatment-resistant status is defined as little or no symptom reduction to at least two antipsychotics at a therapeutic dose for a trial of at least six weeks. The aim of the current study is to determine whether ethnicity and migration are associated with treatment resistance. METHODS: In a sample of 251 participants with schizophrenia spectrum disorders, we conducted cross-sectional assessments to collect information regarding self-identified ethnicity, immigration and treatment history. Ancestry was identified using 292 markers overlapping with the HapMap project. Using a regression analysis, we tested whether a history of migration, ethnicity or genetic ancestry were predictive of treatment resistance. RESULTS: Our logistic regression model revealed no significant association between immigration (OR = 0.04; 95%CI = 0.35-3.07; p = 0.93) and treatment resistant schizophrenia. White Europeans did not show significant association with resistance status regardless of whether ethnicity was determined by self-report (OR = 1.89; 95%CI = 0.89-4.20; p = 0.105) or genetic analysis (OR = -0.73; 95%CI = -0.18-2.97; p = 0.667). CONCLUSION: Neither ethnicity nor migrant status was significantly associated with treatment resistance in this Canadian study. However, these conclusions are limited by the small sample size of our investigation.