Dataset Information

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders.

ABSTRACT:

Background

Patients with schizophrenia spectrum disorders (SSD) have a shortened life expectancy related to cardiovascular diseases. We investigated the association of cognitive, positive, and negative symptoms with cardiometabolic dysregulations in SSD patients.

Methods

Overall, 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) study were included. Cognitive function, positive and negative symptoms were assessed at baseline, 3-year, and 6-year. Cardiometabolic biomarkers were measured at 3-year follow-up. We used linear and multinomial logistic regression models to test the association between cardiometabolic biomarkers and clinical trajectories and performed mediation analyzes, while adjusting for clinical and demographic confounders.

Results

Cognitive performance was inversely associated with increased body mass index (mean difference [β], β_high = -1.24, 95% CI = -2.28 to 0.20, P = 0.02) and systolic blood pressure (β_mild = 2.74, 95% CI = 0.11 to 5.37, P = 0.04). The severity of positive symptoms was associated with increased glycated hemoglobin (HbA1c) levels (β_low = -2.01, 95% CI = -3.21 to -0.82, P = 0.001). Increased diastolic blood pressure (OR_{high-decreased} = 1.04, 95% CI = 1.01 to 1.08, P = 0.02; OR_{high-increased} = 1.04, 95% CI = 1.00 to 1.08, P = 0.048) and decreased high-density lipoprotein (OR _{high-increased} = 6.25, 95% CI = 1.81 to 21.59, P = 0.004) were associated with more severe negative symptoms. Increased HbA1c (OR_moderate = 1.05, 95% CI = 1.01 to 1.10, P = 0.024; OR_high = 1.08, 95% CI = 1.02 to 1.14, P = 0.006) was associated with more severe positive symptoms. These associations were not mediated by antipsychotics.

Conclusions

We showed an association between cardiometabolic dysregulations and clinical and cognitive symptoms in SSD patients. The observed associations underscore the need for early identification of patients at risk of cardiometabolic outcomes.

SUBMITTER: Zhao C

PROVIDER: S-EPMC10964276 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders.

Zhao Chenxu C Habtewold Tesfa Dejenie TD Naderi Elnaz E Liemburg Edith J EJ Bruggeman Richard R Alizadeh Behrooz Z BZ

European psychiatry : the journal of the Association of European Psychiatrists 20231213 1

<h4>Background</h4>Patients with schizophrenia spectrum disorders (SSD) have a shortened life expectancy related to cardiovascular diseases. We investigated the association of cognitive, positive, and negative symptoms with cardiometabolic dysregulations in SSD patients.<h4>Methods</h4>Overall, 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) study were included. Cognitive function, positive and negative symptoms were assessed at baseline, 3-year, and 6-year. Cardiometabolic ...[more]

PMID: 38088065

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Project description:Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Dataset Information

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders.

Background

Methods

Results

Conclusions

Publications

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders.

Similar Datasets

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