[Show abstract][Hide abstract] ABSTRACT: Schizophrenia (SZ) is a brain disorder that has been intensively studied for over a century; yet, its etiology and multifactorial pathophysiology remain a puzzle. However, significant advances have been made in identifying numerous abnormalities in key biochemical systems. One among these is the antioxidant defense system (AODS) and redox signaling. This review summarizes the findings to date in human studies. The evidence can be broadly clustered into three major themes: perturbations in AODS, relationships between AODS alterations and other systems (i.e., membrane structure, immune function, and neurotransmission), and clinical implications. These domains of AODS have been examined in samples from both the central nervous system and peripheral tissues. Findings in patients with SZ include decreased nonenzymatic antioxidants, increased lipid peroxides and nitric oxides, and homeostatic imbalance of purine catabolism. Reductions of plasma antioxidant capacity are seen in patients with chronic illness as well as early in the course of SZ. Notably, these data indicate that many AODS alterations are independent of treatment effects. Moreover, there is burgeoning evidence indicating a link among oxidative stress, membrane defects, immune dysfunction, and multineurotransmitter pathologies in SZ. Finally, the body of evidence reviewed herein provides a theoretical rationale for the development of novel treatment approaches.
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a psychiatric disorder diagnosed by the presence of a number of symptoms with cognitive impairment as a core feature. Long-term antipsychotic treatment is often associated with the emergence of tardive dyskinesia (TD) and the presence of TD is linked to cognitive impairment. This study examined the relationship between TD and cognitive deficits in Chinese patients with schizophrenia.
We recruited 206 chronic patients with TD (n=102) and without TD (n=104) meeting DSM-IV criteria for schizophrenia and 104 control subjects who were matched on age, gender, and education. All the patients completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Symptom Scale (PANSS), and the Abnormal Involuntary Movement Scale (AIMS).
The PANSS total score (p=0.01), N subscore (p=0.006), and AIMS total score (p<0.001) were significantly higher in patients with TD compared to patients without TD. Patients with TD scored lower for visuospatial/constructional, attention, and total index scores (all p<0.001) on the RBANS. AIMS orofacial scores were identified as an independent contributor to RBANS total scores and attention index (p < 0.05), whereas AIMS limb and truncal scores were an independent determinant to the visuospatial/constructional index of RBANS (p<0.05).
TD was associated with greater cognitive impairment in patients with schizophrenia compared to those without TD. The orofacial and limb-trunk TD specifically appeared to be a risk factor or contributor to the different aspects of cognitive deficits in schizophrenia. The association between schizophrenia and TD may be explained in part by oxidative stress.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2013; 46. DOI:10.1016/j.pnpbp.2013.06.013 · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long-term antipsychotic treatment for schizophrenia is often associated with the emergence of tardive dyskinesia (TD), and TD presence is also accompanied by more severe cognitive impairment. Oxidative stress-induced damage may be involved in the development of TD and contribute to cognitive deficits in schizophrenia. We examined the role of oxidative stress in relation to TD and cognitive deficits in schizophrenia using plasma manganese superoxide dismutase (MnSOD) as a biomarker. We recruited 83 male chronic patients with (n=32) and without TD (n=51) meeting DSM-IV criteria for schizophrenia, and 58 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and MnSOD activity for all subjects. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patients. MnSOD activity was lower in patients with TD than non-TD, and either TD or non-TD group had lower MnSOD levels than controls (all p<0.05). Patients with TD had lower RBANS total (p<0.05) and Visuospatial/Constructional subscale scores than non-TD patients (p<0.01), and either TD or non-TD group scored lower than the controls on all RBANS subscales (all p<0.001) except for the Visuospatial/Constructional index. Multiple regression analysis showed that in either TD or non-TD group, MnSOD was an independent contributor to the RBANS total score (both p<0.05). These findings suggest that TD patients suffered oxidative stress and cognition impairment at a more severe level than non-TD patients. Oxidative stress might serve as a functionally linking node between TD development and cognition dysfunction in schizophrenia.
Schizophrenia Research 12/2013; 152(1). DOI:10.1016/j.schres.2013.11.010 · 4.43 Impact Factor
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