Increased Oxidative Stress Toxicity and Lowered Antioxidant Defenses in Temporal Lobe Epilepsy and Mesial Temporal Sclerosis: Associations with Psychiatric Comorbidities

Abstract

Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), play a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown.Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP) and sulfhydryl (-SH) groups in Depression due to TLE (n=25); Anxiety Disorders due to TLE (n=27); Psychotic Disorder due to TLE (n=25); “pure TLE” (n=27); and healthy controls (n=40).TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899) and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, whilst increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels.These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups play a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology, psychosis, as well as negative and depressive symptoms.

Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: Neurocognitive and Symptom Correlates

“…In addition, those authors reported that the ratio of total peroxides versus antioxidants potential was significantly higher in patients with deficit schizophrenia. Nevertheless, our results show that deficit schizophrenia is accompanied by increased oxidative stress toxicity, which attributable to increased AOPP levels [63,64] and that mesial temporal sclerosis is accompanied by highly increased MDA levels, whereas AOPP levels are less severely disordered [62]. Therefore, it appears that increased protein oxidation without severe lipid peroxidation and aldehyde formation is a more specific OS biomarker profile of deficit schizophrenia.…”

Bioinformatic analysis identifies potential key genes of epilepsy

“…It has been shown that ALDH3B1 plays a critical role in the cellular defense against oxidative stress processes and aldehyde toxicity [ 112 , 113 ]. Oxidative stress toxicity and lowered antioxidant defense are considered as contributing factors in the genesis and progression of epilepsy [ 114 – 116 ], while epileptic seizures, especially recurrent seizures may also increase oxidative stress, which will result in treatment resistance [ 117 – 120 ]. Oxidative stress can lead to the occurrence of lipid peroxidation (LPO) and resulting in plenty of aldehydes, such as 4-hydroxy-2-nonenal (4HNE) [ 121 ].…”

Increased neurotoxicity due to activated immune-inflammatory and nitro-oxidative stress pathways in patients with suicide attempts: a systematic review and meta-analysis

“…22,23 Immune activation is frequently associated with activation of oxidative and nitrosative stress (O&NS) pathways and with lowered levels of key antioxidants such as high-density lipoprotein cholesterol (HDL-c) and vitamins including vitamin D. 24,25 There is now evidence that both O&NS and lowered antioxidant levels play a key role in the pathophysiology of affective disorders and schizophrenia. 26,27 In those disorders, increased nitro-oxidative stress in indicated by elevated levels of lipid hydroperoxides (LOOH) and malondialdehyde (both indicating lipid peroxidation), advanced oxidation protein products (indicating increased oxidation of proteins) and nitric oxide (NO) metabolites (NOx). 27,28 Moreover, both disorders are accompanied by lowered levels of key antioxidants including HDL-c, vitamin D, and albumin.…”

“…26,27 In those disorders, increased nitro-oxidative stress in indicated by elevated levels of lipid hydroperoxides (LOOH) and malondialdehyde (both indicating lipid peroxidation), advanced oxidation protein products (indicating increased oxidation of proteins) and nitric oxide (NO) metabolites (NOx). 27,28 Moreover, both disorders are accompanied by lowered levels of key antioxidants including HDL-c, vitamin D, and albumin. 29 The neurotoxicity theories of mood disorders and schizophrenia consider that the neurotoxic effects of immune and O&NS (IO&NS) pathways cause dysfunctions in gray and white matter functional plasticity (including axon sprouting, synaptogenesis, glial changes, neurogenesis, and myelin formation) thereby explaining the onset of affective disorders and schizophrenia.…”

“…26, 27 In those disorders, increased nitro-oxidative stress in indicated by elevated levels of lipid hydroperoxides (LOOH) and malondialdehyde (both indicating lipid peroxidation), advanced oxidation protein products (indicating increased oxidation of proteins) and nitric oxide (NO) metabolites (NOx). 27, 28 Moreover, both disorders are accompanied by lowered levels of key antioxidants including HDL-c, vitamin D, and albumin. 29…”