Abstract
Cognitive deficits represent a core feature of schizophrenia. Previous studies have demonstrated that plasma asymmetric dimethylarginine (ADMA) was increased in patients with schizophrenia and correlated with cognitive impairments. Atypical antipsychotics can produce cognitive benefits in schizophrenia patients. In this study, we conducted a prospective observation trial to explore whether plasma ADMA may serve as an indicator for evaluating cognitive improvements induced by atypical antipsychotics in patients with schizophrenia. A total of 41 schizophrenia patients with acute exacerbation were enrolled and 29 patients completed this study. These recruited patients were drug-naive or had no exposure to antipsychotics for at least 3 months. Thirty healthy individuals were recruited as a control group. Positive and Negative Syndrome Scale (PANSS) and a neuropsychological battery were used to evaluate schizophrenic symptoms and cognitive function, respectively. Plasma ADMA was measured by high-performance liquid chromatography (HPLC). We found that schizophrenia patients with acute exacerbation had significantly poorer cognitive performances and higher plasma ADMA levels than control individuals (p < 0.05). After 2 months of atypical antipsychotic treatment, patients showed significant improvements in processing speed, working memory, attention, and executive function (all p < 0.01). Plasma ADMA levels in patients after treatment were significantly decreased compared to baseline (2.42 ± 0.84 vs. 1.55 ± 0.34 μmol/L; t = 6.491, p < 0.001). Correlation analysis reveals that there is a significant correlation of the decrease in ADMA with improvements in working memory (r = −0.413, p = 0.026) and attention (r = −0.417, p = 0.025). Collectively, our results suggest that atypical antipsychotics improve cognitive function in schizophrenia patients with acute exacerbation, in parallel with decreased plasma ADMA levels. Plasma ADMA levels may be an indicator of cognitive recovery in schizophrenia.
Highlights
Schizophrenia is a chronic mental disorder with a prevalence of ∼1% in the population worldwide
We found that plasma asymmetric dimethylarginine (ADMA) levels were elevated in schizophrenia patients and increased ADMA correlated with cognitive impairment [17]
We investigated whether [1] eight-week atypical antipsychotic monotherapy improves cognition in schizophrenia patients with acute exacerbation; [2] peripheral ADMA is decreased at the endpoint (8th-week) compared to baseline; and [3] improvement of cognition is correlated with change of ADMA levels
Summary
Schizophrenia is a chronic mental disorder with a prevalence of ∼1% in the population worldwide. A large number of cognitive areas including processing speed, attention, visual memory, verbal learning, working memory, and execute capacity have been reported to be impaired in patients with schizophrenia [3, 4]. They are present before the onset of psychosis and may lead to functional disability, including defects in work and social contact, independent living, as well as skill acquirement [5, 6]. Numerous double-blind, random-controlled clinical studies have shown that, in compared to FGAs, treatment of atypical antipsychotics could greatly promote cognitive capability in patients with schizophrenia [9,10,11]. Overall cognitive ability and specific domains of cognition such as processing speed, memory, and attention were improved after the usage of atypical antipsychotics [10, 12]
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