Abstract
A series of studies indicated that iron distribution that partly derives from transferrin-bound iron in the peripheral nervous system in the brain may act in processes such as myelination and brain development. However, the relationship between schizophrenia, its psychotic symptoms, and the transferrin (TF) gene has not been systematically explored. Our study aimed to investigate how a particular polymorphism of the transferrin gene, rs3811655, affects the superoxide dismutase (SOD), malondialdehyde (MDA), psychotic symptoms, cognition, or the mediation model between antioxidant enzymes and cognition via symptoms. A total of 564 patients with chronic schizophrenia and 468 healthy control subjects were recruited. The psychotic symptoms and cognition were assessed by the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Furthermore, the serum SOD, MDA activity, and transferrin gene polymorphism were measured in patients. Our results demonstrated that patients with the G allele possessed more severe negative symptoms, worse cognitive performance with respect to attention, and higher serum Mn-SOD activity. Additionally, the rs3811655 polymorphism may act as a moderator in the association between Cu/Zn-SOD activity and cognition, as well as psychotic symptoms in patients suffering from schizophrenia. According to this study, the single nucleotide polymorphism (SNP) rs3811655 polymorphism may fail to contribute to the susceptibility of schizophrenia in an individual but is involved in the iron-induced oxidative stress disturbance and cognitive impairment in schizophrenia. This deepens our understanding of the critical role of iron-induced oxidative stress that might underlie the pathophysiology of schizophrenia.
Highlights
Schizophrenia patients with severe psychotic symptoms perform poorly in cognitive tasks and cognition, which, in turn, correlates with social and vocational impairment [1].For example, negative and disorganized symptoms are related to poor performance in verbal IQ and concept attainment [1]
In addition to assessing the mediation role of psychotic symptoms on the relations between serum Cu/Zn-superoxide dismutase (SOD)/ Mn-SOD and cognition, we examined whether these mediation models would act differently with the rs3811655 genotype.For the C allele carriers, serum
It was demonstrated that (a) there was no significant correlation between transferrin gene polymorphism and the susceptibility to schizophrenia; (b) rs3811655-G variant was associated with more severe symptoms, worse cognition, and higher SOD activity in schizophrenia; (c) mediation analyses indicated that psychotic symptoms played a fully intermediary role between either Cu/Zn-SOD or Mn-SOD activity and cognition; (d) the mediating role of psychotic symptoms on the relations between
Summary
Schizophrenia patients with severe psychotic symptoms perform poorly in cognitive tasks and cognition, which, in turn, correlates with social and vocational impairment [1].For example, negative and disorganized symptoms are related to poor performance in verbal IQ and concept attainment [1]. Schizophrenia patients with severe psychotic symptoms perform poorly in cognitive tasks and cognition, which, in turn, correlates with social and vocational impairment [1]. Meta-analysis of large cohort studies has proved that prefrontal thickness was significantly correlated with negative symptom severity in schizophrenia after controlling the influences of age, gender, site, and overall illness severity [2]. Twin studies and molecular genetic methods have indicated that the Antioxidants 2022, 11, 125. Antioxidants 2022, 11, 125 link between the majority of the genetic variance in schizophrenia and cognitive performance was small and represents a “weak” association between cognitive impairment and psychosis [3]. As a non-specific indicator of brain malfunction, cognitive deterioration is associated with psychosis, but it is not a trait that can be justified by conventional physiological understanding. It is important to take other disease pathophysiology factors into account
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