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Mental illness and cardiovascular health: observational and polygenic score analyses in a population-based cohort
R R Veeneman1, J M Vermeulen2, M Bialas1
1Genetic Epidemiology, Department of Psychiatry, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands.
Insights
Serious mental illness is linked to cardiovascular disease (CVD). Depressive disorder shows strong associations with arrhythmia and atherosclerosis, even after accounting for confounders.
Area of Science:
- Psychiatry
- Cardiology
- Genetics
Background:
- Serious mental illness is associated with significantly reduced life expectancy, largely due to cardiovascular disease (CVD).
- Investigating the link between mental disorders and CVD is crucial for public health.
- Understanding confounding factors is key to elucidating these associations.
Purpose of the Study:
- To investigate the associations between depressive disorder, bipolar disorder, and schizophrenia (and their genetic liability) with various CVD traits.
- To determine the extent to which these associations are influenced by confounders like medication, demographics, and lifestyle.
- To explore the utility of polygenic scores (PGSs) in understanding the genetic underpinnings of these relationships.
Main Methods:
- Utilized data from the Dutch Lifelines cohort (N=147,337) including self-reported mental illness diagnoses and CVD traits.
- Employed linear mixed-effects models to analyze associations, adjusting for psychotropic medication, demographic, and lifestyle factors.
- Conducted secondary analyses using polygenic scores (PGSs) for the three mental illnesses in a subsample (N=73,965).
Main Results:
- Depressive disorder diagnosis strongly associated with increased arrhythmia and atherosclerosis risk, and lower heart rate variability, persisting after confounder adjustment.
- Positive associations observed between depression PGSs and arrhythmia/atherosclerosis.
- Bipolar disorder showed associations with most CVD traits, diminishing post-adjustment; its PGSs showed no significant links.
- Schizophrenia diagnosis was not directly linked to CVD traits, but its PGSs correlated with increased arrhythmia risk and lower heart rate variability.
- All investigated mental illnesses were linked to lower blood pressure and reduced hypertension risk.
Conclusions:
- Widespread associations exist between mental illness (particularly depressive disorder) and cardiovascular disease, including genetic liability.
- These links persist even after adjusting for significant confounders.
- Further research is needed to clarify the potential causal pathways between mental illness and CVD.
Background:
Individuals with serious mental illness have a markedly shorter life expectancy. A major contributor to premature death is cardiovascular disease (CVD). We investigated associations of (genetic liability for) depressive disorder, bipolar disorder and schizophrenia with a range of CVD traits and examined to what degree these were driven by important confounders.
Methods:
We included participants of the Dutch Lifelines cohort (N = 147 337) with information on self-reported lifetime diagnosis of depressive disorder, bipolar disorder, or schizophrenia and CVD traits. Employing linear mixed-effects models, we examined associations between mental illness diagnoses and CVD, correcting for psychotropic medication, demographic and lifestyle factors. In a subsample (N = 73 965), we repeated these analyses using polygenic scores (PGSs) for the three mental illnesses.
Results:
There was strong evidence that depressive disorder diagnosis is associated with increased arrhythmia and atherosclerosis risk and lower heart rate variability, even after confounder adjustment. Positive associations were also found for the depression PGSs with arrhythmia and atherosclerosis. Bipolar disorder was associated with a higher risk of nearly all CVD traits, though most diminished after adjustment. The bipolar disorder PGSs did not show any associations. While the schizophrenia PGSs was associated with increased arrhythmia risk and lower heart rate variability, schizophrenia diagnosis was not. All mental illness diagnoses were associated with lower blood pressure and a lower risk of hypertension.
Conclusions:
Our study shows widespread associations of (genetic liability to) mental illness (primarily depressive disorder) with CVD, even after confounder adjustment. Future research should focus on clarifying potential causal pathways between mental illness and CVD.
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