Dataset Information

Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by MnSOD Ala-9Val Gene Polymorphism.

ABSTRACT: The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and MnSOD Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients' psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. MnSOD Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by MnSOD Ala-9Val polymorphism.

SUBMITTER: Wang DM

PROVIDER: S-EPMC9598731 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by <i>MnSOD</i> Ala-9Val Gene Polymorphism.

Wang Dong Mei DM Zhu Rong Rong RR Tian Yang Y Uludag Kadir K Chen Jia Jing JJ Zhou Hui Xia HX Wang Li L Kosten Thomas R TR Zhang Xiang Yang XY Zhang Xiang Yang XY

Antioxidants (Basel, Switzerland) 20221004 10

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, <i>MnSOD</i> Ala-9Val polymorphism and co ...[more]

PMID: 36290704

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Project description:ImportanceSchizophrenia is associated with a reduced life expectancy of 15 to 20 years owing to a high prevalence of cardiometabolic disorders. Obesity, a key risk factor for the development of cardiometabolic alterations, is more prevalent in individuals with schizophrenia. Although obesity is linked to the altered reward processing of food cues, no studies have investigated this link in schizophrenia without the confounds of antipsychotics and illness chronicity.ObjectiveTo investigate neural responsivity to food cues in first-episode psychosis without the confounds of antipsychotic medication or illness chronicity.Design, setting, and participantsA case-control study was conducted from January 31, 2015, to September 30, 2018, in London, United Kingdom, of 29 patients with first-episode psychosis who were not taking antipsychotic medication and 28 matched controls.Main outcomes and measuresParticipants completed a food cue paradigm while undergoing a functional magnetic resonance imaging scan. Neural activation was indexed using the blood oxygen level-dependent hemodynamic response. The Dietary Instrument for Nutrition Education was used to measure diet, and the International Physical Activity Questionnaire was used to measure exercise.ResultsThere were no significant differences in age, sex, or body mass index between the 29 patients (25 men and 4 women; mean [SD] age, 26.1 [4.8] years) and 28 controls (22 men and 6 women; mean [SD] age, 26.4 [5.5] years). Relative to controls, patients consumed more saturated fat (t46 = -3.046; P = .004) and undertook less high-intensity (U = 304.0; P = .01) and low-intensity (U = 299.5; P = .005) weekly exercise. There were no group differences in neural responses to food vs nonfood cues in whole-brain or region-of-interest analyses of the nucleus accumbens, insula, or hypothalamus. Body mass index was inversely correlated with the mean blood oxygen level-dependent signal in the nucleus accumbens in response to food vs nonfood cues in controls (R = -0.499; P = .01) but not patients (R = 0.082; P = .70).Conclusions and relevanceRelative to controls, patients with first-episode psychosis who were not taking antipsychotic medication consumed more saturated fat and showed an altered association between body mass index and neural response to food cues in the absence of differences in neural responses to food cues. These findings highlight how maladaptive eating patterns and alterations in the association between body mass index and neural responses to food cues are established early in the course of schizophrenia.

Project description:IntroductionThe MATRICS consensus cognitive battery (MCCB) is the gold standard for neuropsychological assessment in psychotic disorders but is rarely used in low resource settings. This study used the MCCB to determine the prevalence, profile and associations of various exposures with cognitive impairment in Ugandan first-episode psychosis patients.MethodsPatients and matched healthy controls were recruited at Butabika Hospital in Uganda. Clinical variables were first collated, and after the resolution of psychotic symptoms, a neuropsychological assessment of seven cognitive domains was performed using the MCCB. Cognitive impairment was defined as two standard deviations (SD) below the mean in one domain or 1SD below the mean in two domains. Descriptive statistics determined the prevalence and profile of impairment while regression models determined the association between various exposures with cognitive scores while controlling for age, sex and education.ResultsNeuropsychological assessment with the MCCB found the burden of cognitive impairment in first-episode psychosis patients five times that of healthy controls. The visual learning and memory domain was most impaired in first-episode psychosis patients, while it was the working memory domain for the healthy controls. Increased age was associated with impairment in the domains of the speed of processing (p < 0.001) and visual learning and memory (p = 0.001). Cassava-rich diets and previous alternative and complementary therapy use were negatively associated with impairment in the visual learning (p = 0.04) and attention/vigilance domains (p = 0.012), respectively. There were no significant associations between sex, history of childhood trauma, or illness severity with any cognitive domain.ConclusionA significant burden of cognitive impairment in Ugandan first-episode psychosis patients is consistent with prior data from other contexts. However, the profile of and risk factors for impairment differ from that described in such work. Therefore, interventions to reduce cognitive impairment in FEP patients specific to this setting, including dietary modifications, are required.

Dataset Information

Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by MnSOD Ala-9Val Gene Polymorphism.

Publications

Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by <i>MnSOD</i> Ala-9Val Gene Polymorphism.

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