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

journal contribution
posted on 2023-02-20, 03:22 authored by Ana Paula Michelin, Michael HJ Maes, Thitiporn Supasitthumrong, Chusak Limotai, Andressa Keiko Matsumoto, Laura de Oliveira Semeao, Joao Victor de Lima Pedrao, Estefania Gastaldello Moreira, Buranee Kanchanatawan, Decio Sabbatini Barbosa
BACKGROUND: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase 1 (PON1) status may occur in TLE and these psychiatric conditions. AIM: To examine PON1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in TLE. METHODS: 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 controls. The areas under the receiver operating characteristic curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (± 0.037) for MTS. Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (P < 0.0001) and psychopathology (P < 0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination score. CONCLUSION: 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 activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

History

Journal

WORLD JOURNAL OF PSYCHIATRY

Volume

12

Pagination

308-322

Location

United States

ISSN

2220-3206

eISSN

2220-3206

Language

English

Issue

2

Publisher

BAISHIDENG PUBLISHING GROUP INC