Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression,anxiety and psychosis

作     者：Ana Paula Michelin Michael H J Maes Thitiporn Supasitthumrong Chusak Limotai Andressa Keiko Matsumoto Laura de Oliveira Semeão João Victor de Lima Pedrão Estefânia Gastaldello Moreira Buranee Kanchanatawan Décio Sabbatini Barbosa 

作者机构：Health Sciences CenterState University of LondrinaLondrina 86038-440Brazil Department of PsychiatryFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Department of PsychiatryMedical University of PlovdivPlovdiv 4004Bulgaria IMPACT Strategic Research CenterDeakin UniversityGeelong 3220Australia Chulalongkorn Comprehensive Epilepsy Center of ExcellenceKing Chulalongkorn Memorial HospitalThe Thai Red Cross SocietyBangkok 10330Thailand Division of NeurologyDepartment of MedicineFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand 

出 版 物：《World Journal of Psychiatry》 (世界精神病学杂志)

年 卷 期：2022年第12卷第2期

页      面：308-322页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：Supported by Ratchadapisek Research Funds Faculty of Medicine Chulalongkorn University No.RA60/042(to BK) and No.RA61/050(to MM) 

主　　题：Antioxidants Oxidative stress Neuroimmune Major depression Mood disorders Affective disorders 

摘      要：BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and *** in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric *** To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in *** We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal *** areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for *** least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P0.0001)and psychopathology(P0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not *** severity of TLE was significantly associated with psychopathology ***,PON1 CMPAase activity was inversely associated with Mini Mental State Examination *** The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase *** PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative ***1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.