Dataset Information

Endothelial function, folate pharmacogenomics, and neurocognition in psychotic disorders.

ABSTRACT: Cardiovascular disease (CVD) is a well-described complication of schizophrenia, however, mechanisms connecting CVD with other facets of psychotic disorders, such as neurocognition, are not understood. The current study examined folate metabolism as a potential mechanism of CVD and neurocognitive deficits by: 1) using endothelial dysfunction as a biomarker of CVD, and 2) comparing enzymes associated with neurocognition, CVD, and critical to folate metabolism, methylenetetrahydrofolate reductase (MTHFR) and catechol-o-methyl transferase (COMT). Endothelial function was assessed in 147 participants with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified grouped by MTHFR and COMT allele status. Regression models were used to compare neurocognitive performance based on the Brief Assessment of Cognition in Schizophrenia (BACS). Overall, endothelial function predicted BACS composite z-scores after controlling for age, race, level of education, serum folate levels, and MTHFR/COMT risk allele status. Participants with at least one or more MTHFR and/or COMT risk alleles had lower BACS Composite and BACS Symbol Coding adjusted mean z-scores than those with both MTHFR CC and COMT Met/Met genotypes. Thus, endothelial dysfunction may contribute to the neurocognitive deficits seen in psychotic disorders. CVD interventions may not only reduce CVD-related morbidity, but also lessen progressive neurocognitive deficits reported in psychotic disorders.

SUBMITTER: Grove T

PROVIDER: S-EPMC4409513 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Endothelial function, folate pharmacogenomics, and neurocognition in psychotic disorders.

Grove Tyler T Taylor Stephan S Dalack Gregory G Ellingrod Vicki V

Schizophrenia research 20150223 1-3

Cardiovascular disease (CVD) is a well-described complication of schizophrenia, however, mechanisms connecting CVD with other facets of psychotic disorders, such as neurocognition, are not understood. The current study examined folate metabolism as a potential mechanism of CVD and neurocognitive deficits by: 1) using endothelial dysfunction as a biomarker of CVD, and 2) comparing enzymes associated with neurocognition, CVD, and critical to folate metabolism, methylenetetrahydrofolate reductase ( ...[more]

PMID: 25728832

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Project description:BACKGROUND:Across networks, connectivity within the frontoparietal network (FPN) and cingulo-opercular network (CON) exhibits reductions earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems. By leveraging a large sample of patients with psychosis from early to chronic illness stages, this study sought to determine whether the CON and FPN exhibit evidence of accelerated aging in psychotic disorders, confirm associations between network efficiency and cognition, and determine whether reduced network efficiency is observed in early-stage psychosis. METHODS:Resting-state functional magnetic resonance imaging and cognitive data were obtained on 240 patients with psychotic disorder and 178 healthy control participants (HCs). Global efficiency, a measure of functional integration, was calculated for the CON, FPN, subcortical network, and visual network. Associations with age and cognition were assessed and compared between groups. RESULTS:Consistent with accelerated aging, significant group by age interactions reflected significantly stronger relationships between efficiency and age in patients with psychosis than in HCs for both the CON (psychosis: r = -.37; HC: r = -.16) and FPN (psychosis: r = -.31; HC: r = -.05). Accelerated aging was not observed in either the subcortical or visual network, suggesting specificity for cognitive networks that decline earliest in healthy aging. Replicating prior findings, efficiency of both the CON and FPN correlated with cognitive function across all participants (rs > .11, ps < .031). Furthermore, patients with chronic psychosis (p = .004), but not patients with early psychosis (p = .553), exhibited significantly lower FPN efficiency compared with HCs. CONCLUSIONS:Functional integration of higher-order cognitive networks is intact in early psychosis but exhibits evidence of accelerated aging, suggesting the potential for intervention targeting cognition within the early psychosis period.

Project description:Absolute and relative risks of violence are increased in patients with psychotic disorders, but the contribution of triggers for violent acts to these risks is uncertain.To examine whether a range of triggers for violent acts are associated with risks of violence in patients diagnosed with psychotic disorders and in individuals without a psychiatric diagnosis.Using a sample of all individuals born in Sweden between 1958 and 1988 (N?=?3?123?724), we identified patients in the National Patient Register who were diagnosed with schizophrenia spectrum disorders (n?=?34?903) and bipolar disorder (n?=?29?692), as well as unaffected controls (n?=?2?763?012). We then identified, within each subsample, persons who had experienced any of the following triggers for violent acts between January 1, 2001, and December 15, 2013: exposure to violence, parental bereavement, self-harm, traumatic brain injury, unintentional injuries, and substance intoxication. By using within-individual models, we conducted conditional logistic regression to compare the risk of the individual engaging in violent acts in the week following the exposure to a trigger with the risk during earlier periods of equivalent length. All time-invariant confounders (eg, genetic and early environmental influences) were controlled for by this research design and we further adjusted for time-varying sociodemographic factors.Adjusted odds ratios (aORs) of violent crime occurring in the week following the exposure to a trigger event compared with earlier periods.Among the sample of 2?827?607 individuals (1?492?186 male and 1?335?421 female), all of the examined trigger events were associated with increased risk of violent crime in the week following exposure. The largest 1-week absolute risk of violent crime was observed following exposure to violence (70-177 violent crimes per 10?000 persons). For most triggers, the relative risks did not vary significantly by diagnosis, including unintentional injuries (aOR range, 3.5-4.8), self-harm (aOR range, 3.9-4.2), and substance intoxication (aOR range, 3.0-4.0). Differences by diagnosis included parental bereavement, which was significantly higher in patients with schizophrenia spectrum disorders (aOR, 5.0; 95% CI, 3.0-8.1) compared with controls (aOR, 1.7; 95% CI, 1.3-2.2).In addition to identifying risk factors for violence, clarifying the timing of the triggers may provide opportunities to improve risk assessment and management in individuals with psychotic disorders.

Dataset Information

Endothelial function, folate pharmacogenomics, and neurocognition in psychotic disorders.

Publications

Endothelial function, folate pharmacogenomics, and neurocognition in psychotic disorders.

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