High serum creatinine is associated with reduction of psychiatric symptoms in female patients with anti-NMDAR encephalitis
Graphical abstract
Introduction
Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the second most common autoimmune encephalitis characterized by prominent neuropsychiatric symptoms [1]. This disorder is mediated by IgG autoantibodies against the GluN1 subunit of the NMDAR [2]. Patients show different clinical symptoms according to the stage of the disorder, and most cases have psychiatric symptoms, usually at illness onset [3].
Serum creatinine(SCR) is a product of creatine and phosphocreatine metabolism, and the creatine-phosphocreatine-creatinine system is described as an efficient energy buffering system that quickly replenishes ATP to maintain stable energy levels when tissues suddenly need to meet high energy demands, especially in the brain and muscles [4]. Creatine and creatinine have anti-apoptotic, anti-excitotoxic, and anti-oxidative properties, both in vitro and vivo [5]. In brain, creatine and creatinine are not only involved in dendritic and axonal elongation [6] but also in promoting neuronal growth and survival [7]. Several studies have emphasized the neuroprotective effect of SCR in several brain-related disorders due to these properties. For example, high SCR is associated with a low presence of amyotrophic lateral sclerosis(ALS) in Chinese populations [8], accordingly, creatine and creatinine could prevent neuronal loss and minimize damage caused by reactive species in mouse models of ALS [9]. Creatine and creatinine provide significant improvement in motor performance and higher overall survival in transgenic mouse models of Huntington’s disease [10], and they could also protect neurons against amyloid-β neurotoxicity which is a feature of Alzheimer’s disease [11]. Furthermore, creatine supplementation has been reported to improve patients’ symptomatology and behavior in patients with chronic schizophrenia [12].
It remains unclear from previous studies whether higher SCR level plays a protective role against psychiatric symptoms in patients with anti-NMDAR encephalitis. In this cross-sectional study, we analyzed the SCR levels in patients with and without psychiatric symptoms, and the potential association between the SCR levels and the incidence of patients with psychiatric symptoms was assessed by multivariate logistic regression analysis.
Section snippets
Ethics and patients
This study was performed according to the 1964 Declaration of Helsinki and later amendments and approved by the Ethics Committee of the Shandong Provincial Hospital affiliated with Shandong University.
We enrolled 69 patients with anti-NMDAR encephalitis (female:male = 39:30) who were hospitalized in the Department of the Neurology at Shandong Provincial Hospital from January 2014 to October 2020. All the participants involved in this study were diagnosed as anti-NMDAR encephalitis for the first
Psychiatric phenotype of anti-NMDAR encephalitis
The P + group accounted for 53.62 % (n = 37), and the P- group accounted for 46.38 % (n = 32) of the 69 patients with anti-NMDAR encephalitis with a clear chronology of symptoms. In the P + group, the most common psychiatric symptom was psychosis (70.27 %, n = 26), and other psychiatric symptoms in anti-NMDAR encephalitis included mood changes (54.05 %, n = 20), catatonia (29.73 %, n = 11), agitation (18.91 %, n = 7) and anxiety (10.81 %, n = 4) (Fig. 2). Similar to our study, one American
Discussion
To the best of our knowledge, our study was the first to analyze the correlation between SCR levels and psychiatric symptoms in anti-NMDAR encephalitis. Our study found the SCR levels in the P + group were significantly lower than those in the P- group. Higher SCR level was associated with lower incidence of psychiatric symptoms, and multivariate logistic regression analyses showed that the association between the SCR levels and psychiatric symptoms still existed after adjustment for age,
Conclusions
In conclusion, our study showed higher SCR level could be a protective factor for psychiatric symptoms in female patients with anti-NMDAR encephalitis.
CRediT authorship contribution statement
Ningning Wang: Conceptualization, Investigation, Data curation, Writing - original draft, Resources. Ziling Zeng: Writing - review & editing, Methodology. Baojie Wang: Project administration. Danqing Qin: Validation. Tingting Wang: Software. Chunjuan Wang: Formal analysis, Visualization. Shougang Guo: Funding acquisition, Writing - review & editing, Supervision, Resources.
Declaration of Competing Interest
The authors declare no financial or other conflicts of interest.
Acknowledgement
This study was supported by the National Natural Science Foundation of China (No. 81671183)
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