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Molecular Psychiatry Aug 2022Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these...
Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol: https://osf.io/hk2ag ) meta-umbrella systematic review (Web of Science/PubMed/Cochrane Central Register of Reviews/Ovid/PsycINFO, until 05/12/2021) of umbrella reviews reporting associations between potentially modifiable risk factors and ICD/DSM mental disorders, restricted to highly convincing (class I) and convincing (class II) evidence from prospective cohorts. The primary outcome was the global meta-analytical PAF, complemented by sensitivity analyses across different settings, the meta-analytical Generalised Impact Fraction (GIF), and study quality assessment (AMSTAR). Seven umbrella reviews (including 295 meta-analyses and 547 associations) identified 28 class I-II risk associations (23 risk factors; AMSTAR: 45.0% high-, 35.0% medium-, 20.0% low quality). The largest global PAFs not confounded by indication were 37.84% (95% CI = 26.77-48.40%) for childhood adversities and schizophrenia spectrum disorders, 24.76% (95% CI = 13.98-36.49%) for tobacco smoking and opioid use disorders, 17.88% (95% CI = not available) for job strain and depression, 14.60% (95% CI = 9.46-20.52%) for insufficient physical activity and Alzheimer's disease, 13.40% (95% CI = 7.75-20.15%) for childhood sexual abuse and depressive disorders, 12.37% (95% CI = 5.37-25.34%) for clinical high-risk state for psychosis and any non-organic psychotic disorders, 10.00% (95% CI = 5.62-15.95%) for three metabolic factors and depression, 9.73% (95% CI = 4.50-17.30%) for cannabis use and schizophrenia spectrum disorders, and 9.30% (95% CI = 7.36-11.38%) for maternal pre-pregnancy obesity and ADHD. The GIFs confirmed the preventive capacity for these factors. Addressing several potentially modifiable risk factors, particularly childhood adversities, can reduce the global population-level incidence of mental disorders.
Topics: Child; Female; Humans; Pregnancy; Incidence; Mental Disorders; Prospective Studies; Psychotic Disorders; Risk Factors; Meta-Analysis as Topic
PubMed: 35484237
DOI: 10.1038/s41380-022-01586-8 -
Schizophrenia Research Oct 2022Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk of experiencing self-stigma, and some cultures are more stigmatizing towards SSD than... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individuals with schizophrenia spectrum disorders (SSD) are at heightened risk of experiencing self-stigma, and some cultures are more stigmatizing towards SSD than others. The first purpose of this review is to provide an estimate of the relationship between self-stigma and clinical and psychosocial outcomes. The second purpose is to examine how these relationships vary across cultures.
METHOD
Studies reporting correlations between self-stigma and outcome variable(s) were identified through electronic database searches from June 1, 2021, to January 2, 2022. Mean effect sizes were calculated using Fisher's r-to-Z-transformation.
RESULTS
Sixty-three articles (N = 8925, 22 countries) were included in the systematic review and fifty-three articles (N = 7756) were included in the meta-analysis. For the most studied clinical correlates, self-stigma had a moderate, positive correlation with depressive symptoms (r = 0.49, p < .001), a moderate, negative correlation with functioning (r = -0.39, p < .001), and a positive, small correlation with severity of psychotic symptoms (r = 0.29, p < .001), negative symptoms (r = 0.18, p < .001) and positive symptoms (r = 0.13, p = .01). For the most studied psychosocial correlates, self-stigma had a strong, negative correlation with quality of life (r = -0.52, p < .001) and self-esteem (r = -0.55, p < .001). The correlates of self-stigma were similar across cultures.
DISCUSSION
Self-stigma shows strong to small correlations with clinical and psychosocial variables similarly across cultures. More research is needed to examine underlying mechanisms to develop effective interventions.
Topics: Humans; Schizophrenia; Quality of Life; Social Stigma; Self Concept; Psychotic Disorders
PubMed: 35963056
DOI: 10.1016/j.schres.2022.08.001 -
European Neuropsychopharmacology : the... Mar 2024People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies... (Meta-Analysis)
Meta-Analysis Review
People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Cohort Studies; Europe
PubMed: 38368796
DOI: 10.1016/j.euroneuro.2023.12.010 -
Journal of Affective Disorders Mar 2023No systematic review has estimated the consistency and the magnitude of the risk of developing bipolar disorder I-II (BD-I/II) in individuals at clinical high risk for... (Review)
Review
INTRODUCTION
No systematic review has estimated the consistency and the magnitude of the risk of developing bipolar disorder I-II (BD-I/II) in individuals at clinical high risk for bipolar disorder (CHR-BD).
METHODS
PubMed and Web of Science databases were searched until April 2022 in this pre-registered (PROSPERO CRD42022346515) PRISMA-compliant systematic review to identify longitudinal studies in individuals meeting pre-defined CHR-BD criteria. The risk of bias was assessed using the Newcastle-Ottawa Scale, and results were systematically synthesized around CHR-BD criteria across follow-up periods and different subgroups.
RESULTS
Altogether, 13 studies were included reporting on nine prospective independent cohorts (n = 678 individuals at CHR-BD). The mean age of participants was 15.7 years (range 10.1-22.6 years), and 54.2 % were females. The most common CHR-BD subgroup was subthreshold mania (55.5 %), followed by BD-Not Otherwise Specified (BD-NOS: 33.3 %). Development of BD I/II ranged from 7.1 % to 23.4 % after 2 years. Development of BD-I ranged from 3.4 % at 4 years to 23 % at 8 years. Development of BD-II ranged from 10 % at 2 years to 63.8 % at 4 years. The risk of developing BD-I appeared highest in those meeting BD-NOS criteria (23 % at eight years). Predictors of development of BD were identified but remained mostly unreplicated. The quality of the included studies was moderate (NOS = 5.2 ± 1.1).
CONCLUSIONS
Emerging data from research studies point towards the promising utility of CHR-BD criteria. These studies may pave the way to the next generation of research, implementing detection, prognostication, and preventive interventions in individuals at CHR-BD identified and followed in clinical practice.
Topics: Female; Humans; Child; Adolescent; Young Adult; Adult; Male; Bipolar Disorder; Prospective Studies
PubMed: 36657494
DOI: 10.1016/j.jad.2023.01.045 -
Journal of Affective Disorders Apr 2020Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive...
BACKGROUND
Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments.
METHODS
Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts.
RESULTS
The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation.
LIMITATIONS
Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites.
CONCLUSIONS
The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries.
Topics: Chronic Pain; Drug-Related Side Effects and Adverse Reactions; Humans; Ketamine; Reproducibility of Results
PubMed: 32056935
DOI: 10.1016/j.jad.2020.01.120 -
PLoS Medicine Apr 2022Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments.
METHODS AND FINDINGS
To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this.
CONCLUSIONS
In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.
Topics: Cardiovascular Diseases; Heart Failure; Humans; Mental Disorders; Psychotic Disorders; Schizophrenia
PubMed: 35439243
DOI: 10.1371/journal.pmed.1003960 -
European Psychiatry : the Journal of... Feb 2021During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life...
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.
Topics: Humans; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Symptom Assessment
PubMed: 33597064
DOI: 10.1192/j.eurpsy.2021.11 -
Neuropsychiatric Disease and Treatment 2017Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their... (Review)
Review
INTRODUCTION
Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their real-world use remains limited. Understanding attitudes toward these medications may help identify barriers and inform personalized therapy. This literature review evaluated patient and clinician attitudes toward the use of antipsychotics for treating bipolar disorder.
MATERIALS AND METHODS
A systematic search of the Cochrane Library, Ovid MEDLINE, Embase, and BIOSIS Previews identified English language articles published between January 1, 2000, and June 15, 2016, that reported attitudinal data from patients, health care professionals, or caregivers; treatment decision-making; or patient characteristics that predicted antipsychotic use for bipolar disorder. Results were analyzed descriptively.
RESULTS
Of the 209 references identified, 11 met the inclusion criteria and were evaluated. These articles provided attitudinal information from 1,418 patients with bipolar disorder and 1,282 treating clinicians. Patients' attitudes toward antipsychotics were generally positive. Longer duration of clinical stability was associated with positive attitudes. Implementation of psychoeducational and adherence enhancement strategies could improve patient attitudes. Limited data suggest clinicians' perceptions of antipsychotic efficacy and tolerability may have the greatest impact on their prescribing patterns. Because the current real-world evidence base is inadequate, clinician attitudes may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder.
CONCLUSION
Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted.
PubMed: 28919760
DOI: 10.2147/NDT.S139557 -
PloS One 2017The vascular risk attributable to HIV infection is rising. The heterogeneity of the samples studied is an obstacle to understanding whether HIV is a vascular risk across... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
The vascular risk attributable to HIV infection is rising. The heterogeneity of the samples studied is an obstacle to understanding whether HIV is a vascular risk across geographic regions.
OBJECTIVE
To test the hypothesis that HIV infection is a vascular risk factor, and that the risk conferred by HIV varies by geographical region.
DATA SOURCES
A systematic search of publications was carried out in seven electronic databases: PubMed, The Cochrane Library, EMBASE, Web of Science, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from inception to July 2015.
STUDY SELECTION
We included longitudinal studies of HIV+ individuals and their risk of vascular outcomes of ≥ 50 HIV+ cases and excluded studies on biomarkers of vascular disease as well as clinical trials.
DATA EXTRACTION AND SYNTHESIS
Data was extracted by one of the authors and independently confirmed by the other two authors. We used incidence rate (IR), incidence risk ratio (IRR) and hazard ratio (HR) with their 95% confidence intervals as measures of risk.
MAIN OUTCOME
All-death, myocardial infarction (MI), coronary heart disease (CHD), any stroke, ischemic stroke (IS) or intracranial hemorrhage (ICH).
RESULTS
We screened 11,482 references for eligibility, and selected 117 for analysis. Forty-four cohorts represented 334,417 HIV+ individuals, 49% from the United States. Compared with their European counterparts, HIV+ individuals in the United States had higher IR of death (IRR 1.78, 1.69-1.88), MI (IRR 1.61, 1.29-2.01), CHD (IRR 2.27, 1.92-2.68), any stroke (IRR 1.94, 1.59-2.38), IS (IRR 1.56, 1.23-1.98), and ICH (IRR 4.03, 2.72-6.14). Compared with HIV- controls and independent of geographical region, HIV was a risk for death (HR 4.77, 4.55-5.00), MI (HR 1.60, 1.49-1.72), any CHD (HR 1.20, 1.15-1.25), any stroke (HR 1.82, 1.53-2.16), IS (HR 1.27, 1.15-1.39) and ICH (HR 2.20, 1.61-3.02). Use of antiretroviral therapy was a consistent risk for cardiac outcomes, while immunosuppression and unsuppressed viral load were consistent risks for cerebral outcomes.
CONCLUSIONS
HIV should be considered a vascular risk, with varying magnitudes across geographical and anatomical regions. We think that strategies to reduce the HIV-related vascular burden are urgent, and should incorporate the disparities noted here.
Topics: Case-Control Studies; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Demography; Female; Geography; HIV Infections; HIV Seropositivity; Humans; Incidence; Male; Myocardial Infarction; Risk Factors; Treatment Outcome; Vascular Diseases
PubMed: 28493892
DOI: 10.1371/journal.pone.0176686 -
Pharmacology & Therapeutics Aug 2022Almost fifty years after its first introduction into clinical care, clozapine remains the only evidence-based pharmacological option for treatment-resistant... (Review)
Review
Clozapine's multiple cellular mechanisms: What do we know after more than fifty years? A systematic review and critical assessment of translational mechanisms relevant for innovative strategies in treatment-resistant schizophrenia.
Almost fifty years after its first introduction into clinical care, clozapine remains the only evidence-based pharmacological option for treatment-resistant schizophrenia (TRS), which affects approximately 30% of patients with schizophrenia. Despite the long-time experience with clozapine, the specific mechanism of action (MOA) responsible for its superior efficacy among antipsychotics is still elusive, both at the receptor and intracellular signaling level. This systematic review is aimed at critically assessing the role and specific relevance of clozapine's multimodal actions, dissecting those mechanisms that under a translational perspective could shed light on molecular targets worth to be considered for further innovative antipsychotic development. In vivo and in vitro preclinical findings, supported by innovative techniques and methods, together with pharmacogenomic and in vivo functional studies, point to multiple and possibly overlapping MOAs. To better explore this crucial issue, the specific affinity for 5-HTR, D1R, α, and muscarinic receptors, the relatively low occupancy at dopamine D2R, the interaction with receptor dimers, as well as the potential confounder effects resulting in biased ligand action, and lastly, the role of the moiety responsible for lipophilic and alkaline features of clozapine are highlighted. Finally, the role of transcription and protein changes at the synaptic level, and the possibility that clozapine can directly impact synaptic architecture are addressed. Although clozapine's exact MOAs that contribute to its unique efficacy and some of its severe adverse effects have not been fully understood, relevant information can be gleaned from recent mechanistic understandings that may help design much needed additional therapeutic strategies for TRS.
Topics: Antipsychotic Agents; Clozapine; Humans; Receptors, Dopamine D2; Schizophrenia; Schizophrenia, Treatment-Resistant
PubMed: 35764175
DOI: 10.1016/j.pharmthera.2022.108236