title: WONOEP appraisal: Biomarkers of epilepsy-associated comorbidities.
abstract: Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate with epilepsy-associated comorbidities. A reliable biomarker will allow a more accurate diagnosis and improved treatment of epilepsy-associated comorbidities.
authors.affiliation: Department of Neuroscience, IRCCS-"Mario Negri" Institute for Pharmacological Research, Milano, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Ravizza
authors.affiliation: Department of Medical Pharmacology, Epilepsy Research Center, School of Medicine Marmara University, Istanbul, Turkey.
authors.forename: Filiz Y
authors.initials: FY
authors.lastname: Onat
authors.affiliation: Department of Pediatrics, Neurology and Pharmaceutical Sciences, Children's Hospital Colorado, University of Colorado Schools of Medicine and Pharmacy, Aurora, Colorado, U.S.A.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Brooks-Kayal
authors.affiliation: Inserm U1216, Neuroscience Institute, Grenoble, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Depaulis
authors.affiliation: Laboratory of Developmental Neuroscience, Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, U.S.A.|Montefiore/Einstein Comprehensive Epilepsy Center, Montefiore Medical Center, Bronx, New York, U.S.A.
authors.forename: Aristea S
authors.initials: AS
authors.lastname: Galanopoulou
authors.affiliation: Neurology Division, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.
authors.forename: Andrey
authors.initials: A
authors.lastname: Mazarati
authors.affiliation: Neurology Division, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Numis
authors.affiliation: Neurology Division, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.|Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.
authors.forename: Raman
authors.initials: R
authors.lastname: Sankar
authors.affiliation: Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
mesh_terms: D000818:Animals; D015415:Biomarkers; D015897:Comorbidity; D004827:Epilepsy / Q000453:epidemiology*; D006801:Humans; D001523:Mental Disorders / Q000453:epidemiology*; D009422:Nervous System Diseases / Q000453:epidemiology*; D009446:Neurobiology
chemical_list: D015415:Biomarkers
keywords: Cognition; Depression; Epilepsy; Imaging; Neurobehavioral comorbidities; Polymorphisms