Cerebrotendinous xanthomatosis presenting with schizophrenia-like disorder: A case report.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disorder caused by mutations in CYP27A1. Psychiatric manifestations in CTX are rare and nonspecific, and they often lead to considerable diagnostic and treatment delay. CASE SUMMARY: A 33-year-old female patient admitted to the psychiatric ward for presentation of delusions, hallucinations, and behavioral disturbance is reported. The patient presented with cholestasis, cataract, Achilles tendon xanthoma, and cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood. After the characteristic CTX findings on imaging were obtained, a pathological examination of the Achilles tendon xanthoma was refined. Re-placement therapy was then initiated after the diagnosis was clarified by genetic analysis. During hospitalization in the psychiatric ward, the nonspecific psychiatric manifestations of the patient posed difficulty in diagnosis. After the patient's history of CTX was identified, the patient was diagnosed with organic schizophrenia-like disorder, and psychotic symptoms were controlled by replacement therapy combined with antipsychotic medication. CONCLUSION: Psychiatrists should be aware of CTX, its psychiatric manifestations, and clinical features and avoid misdiagnosis of CTX for timely intervention.

Altered brain regional homogeneity is associated with cognitive dysfunction in first-episode drug-naive major depressive disorder: A resting-state fMRI study.

BACKGROUND: Our study aimed to explore the abnormal spontaneous brain activity by regional homogeneity (ReHo) and its association with cognitive function to understand the neuropathology of major depressive disorder (MDD). METHODS: ReHo was used to investigate brain activities of 60 patients with first-episode drug-naive MDD and 60 healthy controls (HCs). Partial correlation analysis was conducted on altered ReHo values and the severity of symptoms and cognitive deficits. Moreover, support vector machine analysis was used to evaluate the accuracy of abnormal ReHo values in distinguishing patients with MDD from HCs. RESULTS: Compared with HCs, patients with MDD showed significantly increased ReHo values in the right cerebellum crus2 and right thalamus and decreased ReHo values in the right angular gyrus (AG) and right precuneus (PCUN). The ReHo values in right cerebellum crus2 and right AG were positively associated with working memory and visual learning, respectively. Furthermore, the combination of ReHo values in the right cerebellum crus2 and right PCUN discriminated the patients with MDD from HCs with specificity, sensitivity, and accuracy of 0.9688, 0.6250, and 0.90, respectively. LIMITATIONS: The design of repeated cross-sectional surveys does not allow analyses of within individual changes. CONCLUSIONS: Our study revealed that the pathophysiology mechanism of cognitive deficits in MDD may be related to abnormal spontaneous brain activity. Moreover, the combination of ReHo values in the right cerebellum crus2 and right PCUN can be used to discriminate patients with MDD from HCs effectively.

Cold atmospheric pressure plasma: A potential physical therapy for rheumatoid arthritis hyperplastic synovium.

The most significant pathological change in rheumatoid arthritis (RA) is synovial hyperplasia within the joint. The production of a series of degrading enzymes and oxidative stress caused by synovial hyperplasia lead to severe bone and cartilage damage in rheumatoid joints. The core effector cell in hyperplastic synovium is fibroblast-like synovium cells, which can invade cartilage, cause inflammation, destroy joints, and show tumor-like anti-apoptosis characteristics. This study focused on the effect of cold atmospheric pressure plasma on proliferative synovium, and the results showed that no synovial hyperplasia, angiogenesis, or inflammatory infiltration was observed after cold atmospheric pressure plasma (CAP) treatment. The molecular and cellular mechanisms also reveal the spontaneous reactive oxygen species (ROS) cascade inducing apoptosis in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells. This study proposes a potential physical therapy method for treating proliferative synovium and also provides ideas for the application of CAP in other types of tumor diseases.

Mutation of the attractin gene impairs working memory in rats.

OBJECTIVE: Attractin (ATRN) is a widely expressed member of the cell adhesion and guidance protein family in humans that is closely related to cellular immunity and neurodevelopment. However, while previous studies in our laboratory have confirmed the effect of ATRN mutations on long-term memory, its specific role and the molecular mechanism by which it influences spatial cognition are poorly understood. METHODS: This study aimed to examine the effect of ATRN mutations on working memory in water maze with a novel ATRN-mutant rat generated by the CRISPR/Cas9 system; the mutation involved the substitution of the 505th amino acid, glycine (G), with cysteine (C), namely, a mutation from GGC to TGC. The changes in myelin basic protein (MBP) expression in rats were also analyzed with the western blot. RESULTS: The ATRN-G505C(KI/KI) rats exhibited significant increases in the required latency and distance traveled to locate the escape platform in a Morris water maze test of working memory. In addition, the expression of MBP was reduced in ATRN-mutant rats, as shown in the western blot analysis. CONCLUSION: Our results indicate that ATRN gene mutations may directly lead to the impairment of working memory in the water maze; this impairment may be due to the inhibition of MBP expression, which in turn affects the spatial cognition.

Identifying and revealing different brain neural activities of cognitive subtypes in early course schizophrenia.

Background: Cognitive subtypes of schizophrenia may exhibit different neurobiological characteristics. This study aimed to reveal the underlying neurobiological features between cognitive subtypes in the early course of schizophrenia (ECS). According to prior studies, we hypothesized to identify 2-4 distinct cognitive subtypes. We further hypothesized that the subtype with relatively poorer cognitive function might have lower brain spontaneous neural activity than the subtype with relatively better cognitive function. Method: Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Resting-state functional magnetic resonance imaging scanning was conducted for each individual. There were 155 ECS individuals and 97 healthy controls (HCs) included in the subsequent analysis. Latent profile analysis (LPA) was used to identify the cognitive subtypes in ECS individuals, and amplitude of low-frequency fluctuations (ALFFs) was used to measure brain spontaneous neural activity in ECS individuals and HCs. Results: LPA identified two cognitive subtypes in ECS individuals, containing a severely impaired subtype (SI, n = 63) and a moderately impaired subtype (MI, n = 92). Compared to HCs, ECS individuals exhibited significantly increased ALFF in the left caudate and bilateral thalamus and decreased ALFF in the bilateral medial prefrontal cortex and bilateral posterior cingulate cortex/precuneus (PCC/PCu). In ECS cognitive subtypes, SI showed significantly higher ALFF in the left precentral gyrus (PreCG) and lower ALFF in the left PCC/PCu than MI. Furthermore, ALFFs of left PreCG were negatively correlated with several MCCB cognitive domains in ECS individuals, while ALFF of left PCC/PCu presented opposite correlations. Conclusion: Our findings suggest that differences in the brain spontaneous neural activity of PreCG and PCC/PCu might be the potential neurobiological features of the cognitive subtypes in ECS, which may deepen our understanding of the role of PreCG and PCC/PCu in the pathogenesis of cognitive impairment in schizophrenia.

Abnormal network homogeneity of default-mode network and its relationships with clinical symptoms in antipsychotic-naïve first-diagnosis schizophrenia.

Schizophrenia is a severe mental disorder affecting around 0.5-1% of the global population. A few studies have shown the functional disconnection in the default-mode network (DMN) of schizophrenia patients. However, the findings remain discrepant. In the current study, we compared the intrinsic network organization of DMN of 57 first-diagnosis drug-naïve schizophrenia patients with 50 healthy controls (HCs) using a homogeneity network (NH) and explored the relationships of DMN with clinical characteristics of schizophrenia patients. Receiver operating characteristic (ROC) curves analysis and support vector machine (SVM) analysis were applied to calculate the accuracy of distinguishing schizophrenia patients from HCs. Our results showed that the NH values of patients were significantly higher in the left superior medial frontal gyrus (SMFG) and right cerebellum Crus I/Crus II and significantly lower in the right inferior temporal gyrus (ITG) and bilateral posterior cingulate cortex (PCC) compared to those of HCs. Additionally, negative correlations were shown between aberrant NH values in the right cerebellum Crus I/Crus II and general psychopathology scores, between NH values in the left SMFG and negative symptom scores, and between the NH values in the right ITG and speed of processing. Also, patients' age and the NH values in the right cerebellum Crus I/Crus II and the right ITG were the predictors of performance in the social cognition test. ROC curves analysis and SVM analysis showed that a combination of NH values in the left SMFG, right ITG, and right cerebellum Crus I/Crus II could distinguish schizophrenia patients from HCs with high accuracy. The results emphasized the vital role of DMN in the neuropathological mechanisms underlying schizophrenia.

Remission of symptoms is not equal to functional recovery: Psychosocial functioning impairment in major depression.

The ultimate goal of depression treatment is to achieve functional recovery. Psychosocial functioning is the main component of functional impairment in depressed patients. The concept of psychosocial functioning has an early origin; however, its concept and connotation are still ambiguous, which is the basic and key problem faced by the relevant research and clinical application. In this study, we start from the paradox of symptoms remission and functional recovery, describe the concept, connotation, and characteristics of psychosocial functioning impairment in depressed patients, and re-emphasize its importance in depression treatment to promote research and clinical applications related to psychosocial functioning impairment in depressed patients to achieve functional recovery.

Association of Reduced Local Activities in the Default Mode and Sensorimotor Networks with Clinical Characteristics in First-diagnosed Episode of Schizophrenia.

The neurodevelopmental hypothesis states that schizophrenia is a brain disease. Exploring abnormal brain activities can improve understanding of the neural pathologic mechanism of clinical characteristics and determine subjective biomarkers to differentiate patients with schizophrenia from healthy controls. We collected clinical characteristics (i.e., demographics, positive and negative syndrome scale (PANSS) scores, and cognitive scores) and magnetic resonance imaging (MRI) data from 57 first-diagnosed drug-naïve patients with schizophrenia and 50 healthy controls. The fractional amplitude of low-frequency fluctuation (fALFF) was used to detect local activities. Partial correlation analysis was applied to estimate the relationship between abnormal regions and clinical characteristics. The support vector machine (SVM) analysis was used to calculate the accuracy of classification in abnormal regions. In our study, the fALFF values in the right postcentral gyrus, left precentral gyrus/postcentral gyrus, left postcentral gyrus/superior parietal lobule, bilateral supplementarymotor area, bilateral paracentral lobule, and bilateral precuneus were decreased in patients with schizophrenia and associated with clinical characteristics. However, the related patterns of cognition of patients were different from those of healthy controls. Additionally, the combination of fALFF values in the bilateral paracentral lobule and right postcentral gyrus might distinguish patients with schizophrenia from healthy controls with high accuracy (98.13%), specificity (98.00%), and sensitivity (98.25%). Our study suggests that reduced local activities in the default mode network and sensorimotor network may be regarded as neural underpinnings of clinical characteristics and may discriminate patients with schizophrenia from healthy controls.

Altered regional homogeneity and cognitive impairments in first-episode schizophrenia: A resting-state fMRI study.

BACKGROUND: Patients with schizophrenia consistently present pervasive cognitive deficits, but the neurobiological mechanism of cognitive impairments remains unclear. By analyzing regional homogeneity (ReHo) of resting-state functional Magnetic Resonance Imaging, this study aimed to explore the association between brain functional alterations and cognitive deficits in first-episode schizophrenia (FES) with a relatively large sample. METHODS: A total of 187 patients with FES and 100 healthy controls from 3 independent cohorts underwent resting-state functional magnetic resonance scans. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive function. Partial correlation analysis was performed between abnormal ReHo values and the severity of symptoms and cognitive deficits. RESULTS: Compared with healthy controls, ReHo values increased in right superior frontal cortex and decreased in right anterior cingulate cortex (ACC), left middle occipital gyrus (MOG), left cuneus, right posterior cingulate cortex (PCC), and right superior occipital gyrus in schizophrenia patients. ReHo values in ACC, PCC and superior occipital gyrus were correlated with PANSS scores. In addition, ReHo values in ACC and MOG were negatively correlated with working memory; left cuneus was positively correlated with multiple cognitive domains (speed of processing, attention/vigilance and social cognition); PCC was positively correlated with verbal learning; right superior occipital gyrus was positively correlated with speed of processing and social cognition. CONCLUSION: In conclusion, we found widespread ReHo alterations and cognitive dysfunction in FES. And the pathophysiology mechanism of a wide range of cognitive deficits may be related to abnormal spontaneous brain activity.

Attractin Participates in Schizophrenia by Affecting Testosterone Levels.

Attractin (ATRN) is a widely expressed glycoprotein that is involved in energy homeostasis, neurodevelopment, and immune response. It is encoded by a gene spanning 180 kb on chromosome 20p13, a region previously implicated in schizophrenia by linkage studies. To address a possible role of ATRN in disorders of the central nervous system, we created an atrn knockout zebrafish line and performed behavioral tests. Adult atrn-/- zebrafish exhibited more pronounced attack behavior relative to wild-type control zebrafish in a tracking analysis. Biochemical analysis revealed elevated testosterone levels in atrn-/- zebrafish. At the gene expression level, we noted an upregulation of cyp51 and hsd17b7, key proteins in testosterone synthesis in the brains of both adult and larvae of atrn-/- zebrafish. In order to further elucidate the relationship between testosterone and behavioral syndromes, we then compared testosterone levels of 9,008 psychiatric patients and 247 healthy controls from the same catchment area. Of all subjects examined, male subjects with schizophrenia exhibited lower testosterone levels compared with controls. In contrast, female subjects with a diagnosis of schizophrenia or bipolar disorder featured higher testosterone levels than did same sex controls. Purposeful sampling of extreme groups showed reduced ATRN expression in a subset of these subjects. Finally, we identified 14 subjects with ATRN mutations. All of whom displayed abnormal testosterone levels. In summary, the interplay of ATRN and testosterone may help to explain sexual dimorphisms in selected behavioral phenotypes.

Enhanced Prefrontal Regional Homogeneity and Its Correlations With Cognitive Dysfunction/Psychopathology in Patients With First-Diagnosed and Drug-Naive Schizophrenia.

Background: Schizophrenia, regarded as a neurodevelopmental disorder, is characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Investigating the spontaneous brain activity in patients with schizophrenia can help us understand the underlying pathophysiologic mechanism of schizophrenia. However, results concerning abnormal neural activities and their correlations with cognitive dysfunction/psychopathology of patients with schizophrenia were inconsistent. Methods: We recruited 57 first-diagnosed and drug-naive patients with schizophrenia and 50 matched healthy controls underwent magnetic resonance imaging. The Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery were used to assess the psychopathology/cognitive dysfunction. Regional homogeneity (ReHo) was used to explore neural activities. Correlation analyses were calculated between abnormal ReHo values and PANSS scores/standardized cognitive scores. Lastly, support vector machine analyses were conducted to evaluate the accuracy of abnormal ReHo values in distinguishing patients with schizophrenia from healthy controls. Results: Patients with schizophrenia showed cognitive dysfunction, and increased ReHo values in the right gyrus rectus, right inferior frontal gyrus/insula and left inferior frontal gyrus/insula compared with those of healthy controls. The ReHo values in the right inferior frontal gyrus/insula were positively correlated with negative symptom scores and negatively correlated with Hopkins verbal learning test-revised/verbal learning. Our results showed that the combination of increased ReHo values in the left inferior frontal gyrus/insula and right gyrus rectus had 78.5% (84/107) accuracy, 85.96% (49/57) sensitivity, and 70.00% specificity, which were higher than other combinations. Conclusions: Hyperactivities were primarily located in the prefrontal regions, and increased ReHo values in the right inferior frontal gyrus/insula might reflect the severity of negative symptoms and verbal learning abilities. The combined increases of ReHo values in these regions might be an underlying biomarker in differentiating patients with schizophrenia from healthy controls.

Identifying Resting-State Multifrequency Biomarkers via Tree-Guided Group Sparse Learning for Schizophrenia Classification.

The fractional amplitude of low-frequency fluctuations (fALFF) has been widely used as potential clinical biomarkers for resting-state functional-magnetic-resonance-imaging-based schizophrenia diagnosis. How-ever, previous studies usually measure the fALFF with specific bands from 0.01 to 0.08 Hz, which cannot fully delineate the complex variations of spontaneous fluctuations in the resting-state brain. In addition, fALFF data are intrinsically constrained by the brain structure, but most of the traditional methods have not consider it in feature selection. For addressing these problems, we propose a model to classify schizophrenia in multifrequency bands with tree-guided group sparse learning. In detail, we first acquire the fALFF data in multifrequency bands (i.e., slow-5: 0.01-0.027 Hz, slow-4: 0.027-0.073 Hz, slow-3: 0.073-0.198 Hz, and slow-2: 0.198-0.25 Hz). Then, we divide the whole brain into different candidate patches and select those significant patches related to schizophrenia using random forest-based important score. Moreover, we use tree-structured sparse learning method for feature selection with the above patch spatial constraint. Finally, considering biomarkers from multifrequency bands can reflect complementary information among multiple-frequency bands, we adopt the multikernel learning method to combine features of multifrequency bands for classification. Our experimental results show that these biomarkers from multifrequency bands can achieve a classification accuracy of 91.1% on 17 schizophrenia patients and 17 healthy controls, further demonstrating that the multifrequency bands analysis can better account for classification of schizophrenia.

Distinguishing Between Treatment-Resistant and Non-Treatment-Resistant Schizophrenia Using Regional Homogeneity.

Background: Patients with treatment-resistant schizophrenia (TRS) and non-treatment-resistant schizophrenia (NTRS) respond to antipsychotic drugs differently. Previous studies demonstrated that patients with TRS or NTRS exhibited abnormal neural activity in different brain regions. Accordingly, in the present study, we tested the hypothesis that a regional homogeneity (ReHo) approach could be used to distinguish between patients with TRS and NTRS. Methods: A total of 17 patients with TRS, 17 patients with NTRS, and 29 healthy controls (HCs) matched in sex, age, and education levels were recruited to undergo resting-state functional magnetic resonance imaging (RS-fMRI). ReHo was used to process the data. ANCOVA followed by post-hoc t-tests, receiver operating characteristic curves (ROC), and correlation analyses were applied for the data analysis. Results: ANCOVA analysis revealed widespread differences in ReHo among the three groups in the occipital, frontal, temporal, and parietal lobes. ROC results indicated that the optimal sensitivity and specificity of the ReHo values in the left postcentral gyrus, left inferior frontal gyrus/triangular part, and right fusiform could differentiate TRS from NTRS, TRS from HCs, and NTRS from HCs were 94.12 and 82.35%, 100 and 86.21%, and 82.35 and 93.10%, respectively. No correlation was found between abnormal ReHo and clinical symptoms in patients with TRS or NTRS. Conclusions: TRS and NTRS shared most brain regions with abnormal neural activity. Abnormal ReHo values in certain brain regions might be applied to differentiate TRS from NTRS, TRS from HC, and NTRS from HC with high sensitivity and specificity.