Christine Doherty1, Tyler G Kinzy2, Lisa Ferguson3, Jessica Altemus4, Bruce P Hermann5, Charis Eng6, Imad Najm7, Robyn M Busch8. 1. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. Electronic address: dohertc@ccf.org. 2. Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 3. Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA. Electronic address: fergusl3@ccf.org. 4. Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: aletmuj@ccf.org. 5. Department of Neurology, University of Wisconsin, Madison, WI, USA. Electronic address: hermann@neurology.wisc.edu. 6. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address: engc@ccf.org. 7. Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA; Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: najmi@ccf.org. 8. Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA; Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: buschr@ccf.org.
Abstract
OBJECTIVE: To explore the role of several genetic polymorphisms (APOE ε4, BDNF Met, and COMT Val) in executive functioning performance in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Ninety-three adults (51 female, mean age = 39 years) with TLE completed executive functioning measures as part of a comprehensive preoperative neuropsychological evaluation, including Trail Making Test (Part B), Wisconsin Card Sorting Test (Conceptual Level Responses and Perseverative Errors), Color Word Interference from the Delis Kaplan Executive Function System, and measures of phonemic and semantic verbal fluency. Genotyping of the APOE, BDNF, and COMT genes was conducted using DNA extracted from peripheral blood or brain tissue (from epilepsy surgery). RESULTS: After adjustment for general cognitive ability, COMT Val carriers showed poorer performance on semantic verbal fluency and color word interference than non-carriers, and BDNF Met carriers showed poorer performance on phonemic verbal fluency than those without a Met allele. SIGNIFICANCE: Results suggest that COMT and BDNF polymorphisms are associated with performance on several EF measures in patients with TLE, including tasks assessing verbal fluency and response inhibition and account for up to 16% of the variance in test performance. The APOE polymorphism was not significantly associated with any of the executive function measures analyzed.
OBJECTIVE: To explore the role of several genetic polymorphisms (APOE ε4, BDNF Met, and COMT Val) in executive functioning performance in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Ninety-three adults (51 female, mean age = 39 years) with TLE completed executive functioning measures as part of a comprehensive preoperative neuropsychological evaluation, including Trail Making Test (Part B), Wisconsin Card Sorting Test (Conceptual Level Responses and Perseverative Errors), Color Word Interference from the Delis Kaplan Executive Function System, and measures of phonemic and semantic verbal fluency. Genotyping of the APOE, BDNF, and COMT genes was conducted using DNA extracted from peripheral blood or brain tissue (from epilepsy surgery). RESULTS: After adjustment for general cognitive ability, COMT Val carriers showed poorer performance on semantic verbal fluency and color word interference than non-carriers, and BDNF Met carriers showed poorer performance on phonemic verbal fluency than those without a Met allele. SIGNIFICANCE: Results suggest that COMT and BDNF polymorphisms are associated with performance on several EF measures in patients with TLE, including tasks assessing verbal fluency and response inhibition and account for up to 16% of the variance in test performance. The APOE polymorphism was not significantly associated with any of the executive function measures analyzed.
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