Christine Doherty1, Olivia Hogue2, Darlene P Floden3, Jessica B Altemus4, Imad M Najm5, Charis Eng6, Robyn M Busch7. 1. Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United States of America. Electronic address: dohertc@ccf.org. 2. Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America. Electronic address: hogueo@ccf.org. 3. Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States of America; Department of Psychiatry & Psychology, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States of America. Electronic address: flodend@ccf.org. 4. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America. Electronic address: altemuj@ccf.org. 5. Cleveland Clinic Epilepsy Center, Neurological Institute, Cleveland, OH, United States of America; Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States of America. Electronic address: najmi@ccf.org. 6. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America. Electronic address: engc@ccf.org. 7. Department of Psychiatry & Psychology, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States of America; Cleveland Clinic Epilepsy Center, Neurological Institute, Cleveland, OH, United States of America. Electronic address: buschr@ccf.org.
Abstract
OBJECTIVE: The objective of this study was to determine whether three common genetic polymorphisms [apolipoprotein (APOE) ε4 (rs42938 and rs7412), brain derived neurotrophic factor (BDNF) Met (rs6265), and catechol-O-methyltransferase (COMT) Val (rs4680)] are associated with increased psychiatric symptomatology in individuals with pharmacoresistant epilepsy. METHODS: One hundred forty-eight adults (Mage = 38 years; 53% female) with refractory epilepsy completed self-report measures of mood, anxiety, and/or personality/psychopathology. Mann-Whitney U, t-tests, and Fisher's exact tests were used to determine if APOE4, BDNF Val66Met, or COMT Val158Met are associated with increased psychiatric symptomatology in people with epilepsy. RESULTS: As a group, BDNF Met carriers reported greater symptoms of depression on the Personality Assessment Inventory (PAI) than those without a Met allele (p = 0.004); COMT Val carriers reported greater symptoms on the PAI Schizophrenia (p = 0.007), Antisocial Features (p = 0.04), and Alcohol Problems (p = 0.03) scales than noncarriers. On the individual level, a significantly greater proportion of BDNF Met carriers demonstrated elevated PAI Depression scores compared to those without a Met allele (p = 0.046). There was also a larger proportion of COMT Val carriers with elevated PAI Anxiety scores as compared to those without a Val allele (p = 0.036). SIGNIFICANCE: This retrospective cross-sectional study provides preliminary evidence for a genetic basis of psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population.
OBJECTIVE: The objective of this study was to determine whether three common genetic polymorphisms [apolipoprotein (APOE) ε4 (rs42938 and rs7412), brain derived neurotrophic factor (BDNF) Met (rs6265), and catechol-O-methyltransferase (COMT) Val (rs4680)] are associated with increased psychiatric symptomatology in individuals with pharmacoresistant epilepsy. METHODS: One hundred forty-eight adults (Mage = 38 years; 53% female) with refractory epilepsy completed self-report measures of mood, anxiety, and/or personality/psychopathology. Mann-Whitney U, t-tests, and Fisher's exact tests were used to determine if APOE4, BDNFVal66Met, or COMT Val158Met are associated with increased psychiatric symptomatology in people with epilepsy. RESULTS: As a group, BDNFMet carriers reported greater symptoms of depression on the Personality Assessment Inventory (PAI) than those without a Met allele (p = 0.004); COMTVal carriers reported greater symptoms on the PAI Schizophrenia (p = 0.007), Antisocial Features (p = 0.04), and Alcohol Problems (p = 0.03) scales than noncarriers. On the individual level, a significantly greater proportion of BDNFMet carriers demonstrated elevated PAI Depression scores compared to those without a Met allele (p = 0.046). There was also a larger proportion of COMTVal carriers with elevated PAI Anxiety scores as compared to those without a Val allele (p = 0.036). SIGNIFICANCE: This retrospective cross-sectional study provides preliminary evidence for a genetic basis of psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population.
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