Autoimmune antibodies in first-episode psychosis with red flags: A hospital-based case-control study protocol.

Background: Research is increasingly identifying an overlap between psychosis and immunological dysregulation. Certain autoantibodies are being identified in a small but probably relevant subgroup of patients with psychosis. The term "autoimmune psychosis" (AIP) and its corresponding red-flag signs present the opportunity for a new field in psychiatry to promote diagnostic workup and immunomodulating therapy in individual cases. Objectives: The present protocol aims to determine the seroprevalence of autoantibodies in first-episode psychosis (FEPs) using AIP red flag signs, and to explore the frequency of autoantibody subtypes and potential mediating confounders. Methods/design: This is a hospital-based case-control study. All participants will be consecutively selected from the main tertiary psychiatric hospital in Shenzhen City, China. Individuals admitted to the psychiatric ward and diagnosed with FEPs will be enrolled. Based on recent consensus, participants with red flags of AIPs will be defined as cases, while the remainder will be matched as controls. Seropositive antibodies will be detected and verified in cerebrospinal fluid (CSF) samples based on the fixed cell-based assay (CBA) method. The propensity score-adjusted odds ratios will be determined to investigate the key mediating confounders regarding autoantibody subtypes and red flag subsets. Discussion: The results of this study will facilitate the early identification of AIPs in FEP patients using the red flag sign and help identify key mediators that improve the accuracy of diagnostic algorithms. It will have clinical significance to focus on serum antibodies that have been verified in CSF samples, due to its consistency with clinical practices in current psychiatry.

Lateralized brain activities in subcortical vascular mild cognitive impairment with differential Chinese medicine patterns: A resting-state functional magnetic resonance imaging study.

Background: Subcortical vascular mild cognitive impairment (svMCI) is one of the most treatable cognitive impairments, but could be hampered by the high clinical heterogeneities. Further classification by Chinese Medicine (CM) patterns has been proved to stratify its clinical heterogeneities. It remains largely unknown of the spontaneous brain activities regarding deficiency patterns (DPs) and excess patterns (EPs) of svMCI patients based on fMRI data. Objective: We aim to provide neuroimaging evidence of altered resting-state brain activities associated with DPs and EPs in svMCI patients. Methods: Thirty-seven svMCI patients (PAs) and 23 healthy controls (CNs) were consecutively enrolled. All patients were categorized into either the EP group (n = 16) and the DP group (n = 21) based on a quantitative CM scale. The fractional amplitude of low-frequency fluctuation (fALFF) value was used to make comparisons between different subgroups. Results: The DP group showed significant differences of fALFF values in the right middle frontal gyrus and the right cerebellum, while the EP group showed significant differences in the left orbitofrontal gyrus and the left cerebellum, when compared with the CN group. When compared with the EP group, the DP group had markedly increased fALFF values in the left superior temporal gyrus, right middle temporal gyrus and brainstem. The decreased fALFF values was shown in the right anterior cingulate and paracingulate gyri. Among the extensive areas of frontotemporal lobe, the Montreal Cognitive Assessment (MoCA) scores were significantly correlated with the reduced fALFF value of the right middle frontal gyrus and the left orbitofrontal gyrus. Conclusion: Our results indicated that the DPs and EPs presented the lateralization pattern in the bilateral frontal gyrus, which will probably benefit the future investigation of the pathogenesis of svMCI patients.

Association Between Late-Onset Leukoencephalopathy With Vanishing White Matter and Compound Heterozygous EIF2B5 Gene Mutations: A Case Report and Review of the Literature.

Leukoencephalopathy with vanishing white matter (LVWM) is an autosomal recessive disease. Ovarioleukodystrophy is defined as LVWM in females showing signs or symptoms of gradual ovarian failure. We present a 38-year-old female with ovarioleukodystrophy who showed status epilepticus, gait instability, slurred speech, abdominal tendon hyperreflexia, and ovarian failure. Abnormal EEG, characteristic magnetic resonance, and unreported EIF2B5 compound heterozygous mutations [c.1016G>A (p.R339Q) and c.1157G>A (p.G386D)] were found. Furthermore, the present report summarizes 20 female patients with adult-onset ovarioleukodystrophy and EIF2B5 gene mutations. In conclusion, a new genetic locus for LVWM was discovered. Compared with previous cases, mutations at different EIF2B5 sites might have different clinical manifestations and obvious clinical heterogeneity.

Psychotic Symptoms as the Initial Presentation of a Long-Lasting Misdiagnosed Anti-GAD65 Autoimmune Encephalitis: An Emblematic Case and Literature Review.

Objective: To present a long-lasting misdiagnosed case of anti-GAD65 autoimmune encephalitis (AE) and promote the early identification of reversible psychotic symptoms in AE. Methods: The case report was generated through detailed assessment of clinical characteristics, cerebral magnetic resonance images, and laboratory results. Meanwhile, a literatures review related to the topic was conducted. Results: Psychotic symptoms could be presented in the early stage of anti-GAD65 autoimmune encephalitis. Even though there exists a transdisciplinary gap that hinder the timely recognition of early psychiatric symptoms as components of organic disease, a few strategies could be introduced to enable the earlier recognition and appropriate treatment. Conclusions: Our report intends to raise awareness to promote the early identification of immune-mediated "symptomatic" forms of psychosis.

Monoclonal Antibody Therapy in Neuromyelitis Optica Spectrum Disorders: a Meta-analysis of Randomized Control Trials.

Background: To update the efficacy and safety data of monoclonal antibodies for the treatment of neuromyelitis optica spectrum disorders (NMOSD) and explore the differences in the effect of treatment between patients seropositive and seronegative for AQP4-IgG. METHODS: PubMed, Embase, and the Cochrane Library published up to July 2020 were searched for randomized controlled trials (RCTs) of monoclonal antibodies treatment (mAb) in patients with NMOSD. The primary outcome was the hazard ratio (HR) for relapse. The secondary outcomes included Expanded Disability Status Scale (EDSS) changes from baseline, adverse events (AEs), and serious adverse events (SAEs). A random-effects model was applied for the effect of heterogeneity among trials. RESULTS: We included 603 patients (monoclonal antibody group, n=382, and control group, n=221) from seven RCTs. There were fewer relapses in the mAb group (HR=0.32, 95% CI: 0.23-0.46, p<0.001), as well as in the AQP4-IgG-seropositive patients (HR=0.18, 95% CI: 0.10-0.32, p<0.001), but not in AQP4-IgG-seronegative NMOSD. Similar results were observed when considering satralizumab only. The mAb had no impact on the changes in EDSS scores from baseline (WMD=-0.21, 95% CI: -0.50-0.09, p=0.176). The mAb did not lead to a higher frequency of AEs (OR=1.18, 95% CI: 0.70-1.98, p=0.529) or SAEs (OR=0.99, 95% CI: 0.63-1.56, p=0.975) compared with the control group. CONCLUSIONS: Compared to the control arm, monoclonal antibody therapy showed a significantly better outcome in restraining the HR for relapse among patients with NMOSD but insignificant effects in NMOSD patients with seronegative APQ4-IgG. The safety profile in each arm had no significant difference.

Cortical Alterations Are Associated with Depression in Subcortical Vascular Mild Cognitive Impairment Revealed by Surface-Based Morphometry.

BACKGROUND: Late-life depression often coexists with vascular cognitive impairment and affects the quality of life for elders. However, little is known about cortical morphometric interactions between subcortical vascular mild cognitive impairment (svMCI) and concomitant mild depressive symptoms at the early stage. OBJECTIVE: We aimed to investigate cortical alterations of svMCI with and without depressive symptoms and determine whether these parameters are associated with depression symptoms and/or cognitive impairments. METHODS: Surface based morphometry was performed on 18 svMCI patients with depressive symptoms (svMCI + D), 16 svMCI patients without depressive symptoms (svMCI-D), and 23 normal controls (NC). RESULTS: Compared to NC, both svMCI + D and svMCI-D patients exhibited significantly decreased surface area (SA) in many cortical areas. Interestingly, svMCI + D patients showed significantly increased rather than decreased SA in right lateral occipital gyrus (LOG.R), and a consistent trend of increased SA in these areas compared to svMCI-D. In addition, the svMCI + D showed increased gray matter volume of left pericalcarine (periCAL.L) than svMCI-D, whereas svMCI-D showed decreased gray matter volume of periCAL.L than NC. Further correlation analyses revealed that the SA of left superior temporal gyrus (STG.L) and right lateral orbital part of frontal gyrus (lorbFG.R) were significantly correlated with Hamilton depression rating scale of svMCI + D. CONCLUSION: In conclusion, these results extend our insight into svMCI and add weight to reevaluation of concomitant early stage depressive symptoms. Moreover, we suggest that LOG.R∖periCAL.L∖STG.L∖lorbFG.R might serve as sensitive and trait-dependent biomarkers to detect concomitant depressive symptoms in svMCI patients.

Hydroxysafflor Yellow A Exerts Anti-Inflammatory Effects Mediated by SIRT1 in Lipopolysaccharide-Induced Microglia Activation.

Abnormal microglia activation causes sever neuroinflammation, contributing to the development of many diseases, yet the mechanism remains incompletely unknown. In current study, we identified that Hydroxysafflor yellow A (HYA), a chalcone glycoside derived from Carthamus tinctorius L effectively attenuates LPS-induced inflammation response in primary microglia via regulating the expression of inflammatory genes and remodeling the polarization of microglia. We also reported the effects of HYA on improving lipopolysaccharide (LPS)-stimulated mitochondrial dysfunction and oxidative stress for the first time. Interestingly, we found that HYA could serves as an effective SIRT1 activator. Deficiency of SIRT1 abrogates the protective effects of HYA against LPS-induced response. Overall, our data suggest HYA, a novel SIRT1 activator, could serve as an effective approach to treat LPS-induced neurodegenerative diseases.

Astragalus polysaccharide alleviates cognitive impairment and ß-amyloid accumulation in APP/PS1 mice via Nrf2 pathway.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its etiology and pathogenesis are not fully understood. Astragalus polysaccharide (APS) has many pharmacological activities, but there are few reports about its role in AD. Using the common AD model APP/PS1 mice, it was found that the expression of Keap1 (a negative regulatory factor of Nrf2), the protein level of cytoplasmic Nrf2 and the content of MDA were increased significantly, while the mRNA level of Nrf2, the expression of Nrf2 in nucleus and the contents of SOD and GSH-Px were decreased significantly. APS treatment significantly increased the expression of Nrf2 in the nucleus but decreased its expression in the cytoplasm, and restored the expression levels of Keap1, SOD, GSH-Px and MDA. When APP/PS1 mice were treated with APS and injected with Nrf2 siRNA, the down-regulation of Nrf2 expression significantly blocked the regulation of APS on oxidative stress. Continuing to test the physiological function of AD mice showed that the spatial learning and memory abilities of APP/PS1 mice were impaired, the apoptosis of brain cells and the content of ß-amyloid (Aß) were significantly increased. APS treatment significantly improved the cognitive ability of APP/PS1 mice, reduced apoptosis and the accumulation of Aß, but the above effects of APS were blocked by Nrf2 siRNA injection. Therefore, APS can activate Nrf2 pathway to improve the physiological function of AD mice, which may have important clinical application value.

The Neuroprotective Effects of Danggui-Shaoyao San on Vascular Cognitive Impairment: Involvement of the Role of the Low-Density Lipoprotein Receptor-Related Protein.

Effective drugs for treating dementia are still rare. Danggui-Shaoyao San (DSS), a traditional Chinese medicine, has been widely used in oriental countries for the treatment of various gynecological diseases. Many studies reported that DSS could ameliorate cognitive impairment. In this study, we aimed to investigate the underlying mechanism of DSS on vascular cognitive impairment (VCI) rats. Chronic cerebral hypoperfusion (CCH) is one of the main causes of VCI. CCH resulted in a chain of pathological process, including neuroinflammation, neuronal apoptosis, and oxidative stress. The most widely used animal model of VCI is permanent bilateral common carotid artery occlusion in rats. In this research, we determined whether DSS attenuated cognitive impairment by targeting I kappa B kinase (IKK)/nuclear factor of kappa B (NF-κB) signal pathway in VCI rats. Morris water maze and fear conditioning tests results indicated that DSS [7.2 g/(kg·d)] could improve learning and memory ability in VCI rats. We also found DSS significantly elevated the levels of low-density lipoprotein receptor-related protein 1 (LRP1) in the brain of VCI rats and this might indirectly target the IKK/NF-κB signal pathway to exert inhibitory effect on neuroinflammation, neuronal apoptosis, and oxidative stress in VCI rats. The present researches indicated that DSS might attenuate cognitive impairment by targeting IKK/NF-κB signal pathway in VCI rats and DSS might be a promising agent on VCI.

Structural and Functional Disruptions in Subcortical Vascular Mild Cognitive Impairment With and Without Depressive Symptoms.

Many previous studies have revealed structural and functional abnormalities in patients with the subcortical vascular mild cognitive impairment (svMCI). Although depression symptoms were suggested to serve as a potential marker of conversion to dementia in patients with svMCI, whether these disruptions or other new findings will be identified in the svMCI comorbid with depression symptoms has not been established. In the current study, we combined voxel-based morphometry (VBM) and the resting-state functional magnetic resonance imaging (fMRI) to investigate the structural and functional disruptions in the svMCI with and without depression symptoms using a cohort of 18 svMCI with depression symptoms (svMCI+D), 17 svMCI without depression symptoms (svMCI-D), and 23 normal controls (NC). As a result, we identified significantly decreased gray matter density in the left parahippocampus (ParaHIPP.L), the right hippocampus (HIPP.R), and the right middle cingulate cortex (MCC.R) in both svMCI+D and svMCI-D compared to NC. Most importantly, we also identified increased gray matter density in the MCC.R accompanied by increased resting-state functional connectivity (RSFC) with right parahippocampus (ParaHIPP.R) in the svMCI+D compared to svMCI-D. Moreover, the gray matter density of MCC.R and ParaHIPP.L was correlated with cognitive impairments and depression symptoms in the svMCI, respectively. In conclusion, these results extended previous studies and added weight to considerations of depression symptoms in the svMCI. Moreover, we suggested that a processing loop associated with HIPP, ParaHIPP, and MCC might underlie the mechanism of depression symptoms in the svMCI.