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Considering medication exposure in genomic association studies of cognition in psychotic disorders
Seenae Eum1, Scot Kristian Hill2, Jeffrey R Bishop3,4
1Department of Pharmacogenomics, School of Pharmacy, Shenandoah University, Fairfax, VA 22031, USA.
Abstract:
Cognitive dysfunction is a core feature of psychosis-spectrum illnesses, and the characterization of related genetic mechanisms may provide insights regarding the disease pathophysiology. Substantial efforts have been made to determine the genetic component of cognitive symptoms, without clear success. Illness-related moderators and environmental factors such as medications hinder the detection of genomic association with cognition. Polypharmacy is common in psychotic disorders, and the cumulative effects of medication regimens can confound gene-cognition associations. A review of the relative contributions of important pharmacological and genetic relationships identifies that the effects of medications on cognition in psychotic disorders may be at least, if not more, impactful than individual genes, thus underscoring the importance of accounting for medication exposure in gene-cognition association studies.
Insights
Medications significantly impact cognition in psychosis-spectrum illnesses, potentially more than genetics. Accounting for medication exposure is crucial for accurate gene-cognition association studies in these disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Cognitive dysfunction is a primary characteristic of psychosis-spectrum illnesses.
- Understanding the genetic underpinnings of cognitive symptoms is vital for disease pathophysiology insights.
- Previous genetic studies have faced challenges in identifying clear associations with cognitive deficits.
Purpose of the Study:
- To review the contributions of pharmacological and genetic factors to cognitive function in psychosis.
- To highlight the confounding effects of medications on gene-cognition association studies.
- To emphasize the importance of considering medication exposure in genetic research for cognitive disorders.
Main Methods:
- Literature review focusing on gene-cognition associations in psychosis-spectrum disorders.
- Analysis of the impact of illness-related moderators and environmental factors, particularly medications.
- Evaluation of the relative influence of pharmacological regimens versus individual genes on cognition.
Main Results:
- Medication regimens, especially polypharmacy, can significantly confound gene-cognition associations.
- The impact of medications on cognition in psychotic disorders may outweigh that of individual genes.
- Current genetic association studies may be hindered by unaddressed medication effects.
Conclusions:
- Medication effects are a critical confounder in genetic studies of cognition in psychosis.
- Future research must rigorously account for medication exposure to accurately identify genetic contributions to cognitive dysfunction.
- Pharmacological interventions may play a more substantial role in cognitive outcomes than previously recognized in genetic studies.
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