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Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

ABSTRACT: Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population.

SUBMITTER: Blokland GAM

PROVIDER: S-EPMC5472145 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

Blokland Gabriëlla A M GAM Mesholam-Gately Raquelle I RI Toulopoulou Timothea T Del Re Elisabetta C EC Lam Max M DeLisi Lynn E LE Donohoe Gary G Walters James T R JTR Seidman Larry J LJ Petryshen Tracey L TL

Schizophrenia bulletin 20170701 4

Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The prop ...[more]

PMID: 27872257

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Project description:BackgroundPsychiatric comorbidity is known to impact upon use of nonpsychiatric health services. The aim of this systematic review and meta-analysis was to assess the specific impact of severe mental illness (SMI) on the use of inpatient, emergency, and primary care services for nonpsychiatric medical disorders.Methods and findingsPubMed, Web of Science, PsychINFO, EMBASE, and The Cochrane Library were searched for relevant studies up to October 2018. An updated search was carried out up to the end of February 2020. Studies were included if they assessed the impact of SMI on nonpsychiatric inpatient, emergency, and primary care service use in adults. Study designs eligible for review included observational cohort and case-control studies and randomised controlled trials. Random-effects meta-analyses of the effect of SMI on inpatient admissions, length of hospital stay, 30-day hospital readmission rates, and emergency department use were performed. This review protocol is registered in PROSPERO (CRD42019119516). Seventy-four studies were eligible for review. All were observational cohort or case-control studies carried out in high-income countries. Sample sizes ranged from 27 to 10,777,210. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies. The majority of studies (n = 45) were deemed to be of good quality. Narrative analysis showed that SMI led to increases in use of inpatient, emergency, and primary care services. Meta-analyses revealed that patients with SMI were more likely to be admitted as nonpsychiatric inpatients (pooled odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.21-2.80, p = 0.005, I2 = 100%), had hospital stays that were increased by 0.59 days (pooled standardised mean difference = 0.59 days, 95% CI 0.36-0.83, p < 0.001, I2 = 100%), were more likely to be readmitted to hospital within 30 days (pooled OR = 1.37, 95% CI 1.28-1.47, p < 0.001, I2 = 83%), and were more likely to attend the emergency department (pooled OR = 1.97, 95% CI 1.41-2.76, p < 0.001, I2 = 99%) compared to patients without SMI. Study limitations include considerable heterogeneity across studies, meaning that results of meta-analyses should be interpreted with caution, and the fact that it was not always possible to determine whether service use outcomes definitively excluded mental health treatment.ConclusionsIn this study, we found that SMI impacts significantly upon the use of nonpsychiatric health services. Illustrating and quantifying this helps to build a case for and guide the delivery of system-wide integration of mental and physical health services.

Project description:BackgroundAlthough expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses.Methods and findingsBibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I(2) = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I(2) = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7-2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4-14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7-25.8).ConclusionsSchizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse. Please see later in the article for Editors' Summary.

Project description:Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function. Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis. Results: 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n = 343), LSD (5 studies, n = 135), and peyote (1 study, n = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study (n = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task (p = 0.03) and no differences in the others (all p > 0.05). Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.

Project description:INTRODUCTION:Glaucoma is the second leading cause of age-related vision loss worldwide; it is an umbrella term that is used to describe a set of complex ocular disorders with a multifactorial aetiology. Both genetic and lifestyle risk factors for glaucoma are well established. Thus far, however, systematic reviews on the heritability of glaucoma have focused on the heritability of primary open-angle glaucoma only. No systematic review has comprehensively reviewed or meta-analysed the heritability of other types of glaucoma, including glaucoma-related endophenotypes. The aim of this study will be to identify relevant scientific literature regarding the heritability of both glaucoma and related endophenotypes and summarise the evidence by performing a systematic review and meta-analysis. METHODS AND ANALYSIS:This systematic review will follow the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 checklist, which provides a standardised approach for carrying out systematic reviews. To capture as much literature as possible, a comprehensive step-by-step systematic search will be undertaken in MEDLINE (PubMed), EMBASE, Web of Science and ScienceDirect, and studies published until 31 December 2017 will be included. Two reviewers will independently search the articles for eligibility according to predefined selection criteria. A database will be used for screening of eligible articles. The quality of the included studies will be rated independently by two reviewers, using the National Health Institute Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. A random-effects model will be used for the meta-analysis. This systematic review is registered with the International Prospective Register of Systematic Reviews with a registration number: CRD42017064504. ETHICS AND DISSEMINATION:We will use secondary data from peer-reviewed published articles, and hence there is no requirement for ethics approval. The results of this systematic review will be disseminated through publication in a peer-reviewed scientific journal.

Project description:Background and objectiveThe genetic basis of dentoalveolar characteristics has been investigated by several studies, however, the findings are equivocal. The objective of this systematic review and meta-analysis was to evaluate the heritability of dental arches and occlusal parameters in different stages of human dentition.Search methodsElectronic databases PubMed, Embase, Scopus, Web of Science, and Dentistry and Oral Science Source were searched up to August 2023 without the restriction of language or publication date.Selection criteriaEmpirical studies investigating the heritability of dentoalveolar parameters among twins and siblings were included in the review.Data collection and analysisStudy selection, data extraction, and risk of bias assessment were performed independently and in duplicate by two authors and a third author resolved conflicts if needed. Joanna Briggs Institute's critical appraisal tool was used to evaluate the risk of bias among studies and the certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria.ResultsTwenty-eight studies were included in the systematic review, of which 15 studies reporting heritability coefficients in the permanent dentition stages were deemed suitable for the meta-analysis. Random-effects meta-analyses showed high heritability estimates for maxillary intermolar width (0.52), maxillary intercanine width (0.54), mandibular intermolar width (0.55), mandibular intercanine width (0.55), maxillary arch length (0.76), mandibular arch length (0.57), and palatal depth (0.56). The heritability estimates for the occlusal parameters varied considerably, with relatively moderate values for crossbite (0.46) and overbite (0.44) and low values for buccal segment relationship (0.32), overjet (0.22), and rotation and displacement of teeth (0.16). However, the certainty of evidence for most of the outcomes was low according to the GRADE criteria.ConclusionsBased on the available evidence, it can be concluded that the dental arch dimensions have a high heritability while the occlusal parameters demonstrate a moderate to low heritability.RegistrationPROSPERO (CRD42022358442).

Dataset Information

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

Publications

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

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