Serum proteomics analysis of drug-naïve patients with generalised anxiety disorder: Tandem mass tags and multiple reaction monitoring.

OBJECTIVES: The prevalence of generalised anxiety disorder (GAD) is high. However, the underlying mechanisms remain elusive. Proteomics techniques can be employed to assess the pathological mechanisms involved in GAD. METHODS: Twenty-two drug-naive GAD patients were recruited, their serum samples were used for protein quantification and identified using Tandem Mass Tag and Multiple Reaction Monitoring (MRM). Machine learning models were employed to construct predictive models for disease occurrence by using clinical scores and target proteins as input variables. RESULTS: A total of 991 proteins were differentially expressed between GAD and healthy participants. Gene Ontology analysis revealed that these proteins were significantly associated with stress response and biological regulation, suggesting a significant implication in anxiety disorders. MRM validation revealed evident disparities in 12 specific proteins. The machine learning model found a set of five proteins accurately predicting the occurrence of the disease at a rate of 87.5%, such as alpha 1B-glycoprotein, complement component 4 A, transferrin, V3-3, and defensin alpha 1. These proteins had a functional association with immune inflammation. CONCLUSIONS: The development of generalised anxiety disorder might be closely linked to the immune inflammatory stress response.

Altered Functional Connectivity in Working Memory Network After Acute Sleep Deprivation.

Acute sleep deprivation (SD) has a detrimental effect on working memory (WM). However, prior functional magnetic resonance imaging (fMRI) studies have failed to reach consistent results on brain functions underlying WM decline after acute SD. Thus, we aimed to identify convergent patterns of abnormal brain functions due to WM decline after acute SD. A coordinate-based activation likelihood estimation (ALE) meta-analysis of task-state fMRI studies testing the effects of acute SD on WM was performed to construct WM network. Then 26 healthy subjects with regular sleep performed the n-back task and underwent resting-state fMRI scanning before and after 24 h of SD. The functional connectivity (FC) among these brain regions and correlations with WM performance were calculated. The ALE results displayed that SD subjects performing WM-related tasks had consistent hypoactivation in the occipital lobe, left middle occipital gyrus, parietal lobe, precuneus, inferior parietal lobule, right sub-gyral, right cuneus, right limbic lobe, and right posterior cingulate. Consistent hyperactivation was showed in the left cerebrum, including the lingual gyrus, posterior lobe, cuneus, temporal lobe, and fusiform gyrus. These identified brain regions as the seeds to construct WM network. The increased FC between the left declive and right sub-gyral, left cuneus and left lingual gyrus, and left cuneus and right post cingulate were found. Furthermore, the impaired WM performance negatively correlated with increased FC. Taken together, our findings highlight that the altered FC in WM network may be the underlying mechanisms of WM decline after acute SD.

Altered Functional Connectivity of Large-Scale Brain Networks in Psychogenic Erectile Dysfunction Associated with Cognitive Impairments.

Purpose: Several studies have demonstrated that psychogenic erectile dysfunction (pED) patients potentially suffer from cognitive dysfunction. Despite that previous neuroimaging studies have reported abnormal functional connections of brain areas associated with cognitive function in pED, the underlying mechanisms of cognitive dysfunction in pED remain elusive. This study aims to investigate the underlying mechanisms of cognitive dysfunction by analyzing large-scale brain networks. Patients and Methods: A total of 30 patients with pED and 30 matched healthy controls (HCs) were recruited in this study and scanned by resting-state functional magnetic resonance imaging. The Dosenbach Atlas was used to define large-scale networks across the brain. The resting-state functional connectivity (FC) within and between large-scale brain networks was calculated to compare pED patients with HCs. The relationship among cognitive performances and altered FC of large-scale brain networks was further explored in pED patients. Results: Our results showed that the decreased FC within visual network, and between visual network and default mode network, visual network and frontoparietal network, and ventral attention and default mode network were found in pED patients. Furthermore, there was a positive correlation between immediate memory score and FC within visual network. The visuospatial score was negatively correlated with decreased FC between ventral attention network and default mode network. Conclusion: Taken together, our findings revealed the relationship between cognitive impairments and altered FC between large-scale brain networks in pED patients, providing the new evidence about the neural mechanisms of cognitive dysfunction in pED patients.

Altered functional connectivity after acute sleep deprivation reveals potential locations for noninvasive brain stimulation techniques.

BACKGROUNDS: Non-invasive brain stimulation (NIBS) techniques are emerging as efficacious treatments for sleep deprivation (SD). However, the stimulation location of NIBS (e.g. transcranial magnetic stimulation and transcranial direct current stimulation) on intervening acute SD is limited in previous studies. In this study, we aimed to investigate potentially effective targets of NIBS on intervening acute SD. METHODS: We firstly performed a meta-analysis of 95 functional magnetic resonance imaging studies to find SD-related brain regions as regions of interest (ROI). Subsequently, we used resting-state functional connectivity analysis in 32 young individuals suffering from 24 h SD to identify brain surface regions associated with the ROIs. Finally, we applied 10-20 system coordinates to locate scalp sites for NIBS corresponding to the brain surface regions. RESULTS: We identified the bilateral dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, left supplementary motor area, precentral, right precuneus, bilateral inferior parietal gyrus, right middle temporal gyrus, and superior frontal gyrus as potential targets of NIBS for intervening SD. The 10-20 system coordinates corresponding to these brain surface regions were identified as potential sites for NIBS. CONCLUSIONS: In conclusion, we identified several potential targets which could provide alternative stimulation locations for the use of NIBS on young patients suffering from acute SD.

Altered White Matter Structural Network Connectivity Associated with Cognitive Declines in Psychogenic Erectile Dysfunction.

It has been reported that individuals with psychogenic erectile dysfunction (pED) potentially suffer from cognitive declines. Despite that increasing neuroimaging studies have demonstrated abnormalities of cerebral structural changes in pED, the association between altered white matter (WM) structural network and cognitive impairments remains unclear. Hence, this study aimed to explore the relationship between WM structural network connectivity and cognitive performance in patients with pED. Forty pED patients and 33 healthy controls (HCs) were recruited to perform cognitive assessments, and diffusion tensor imaging scans. We firstly constructed the WM structural network and applied the machine learning method to identify the important features. Then, we examined group differences in cognitive assessments, WM structural network connectivity within the identified features, and associations between altered WM structural network connectivity and cognitive scores in pED patients. From 26,896 features of DTI data, 24 important features were identified by K-Nearest Neighbor classification with a satisfactory accuracy (78%). Compared with HCs, we found that pED patients showed higher fractional anisotropy (FA) values between left transverse temporal sulcus and left supramarginal gyrus, and lower FA values between left suborbital sulcus and left para-hippocampal part of the medial occipito-temporal gyrus in pED patients. Furthermore, the increased FA between left transverse temporal sulcus and left supramarginal gyrus was observed to be negatively associated with impaired delayed memory. Overall, our findings provide new insights into WM network alterations associated with impaired cognitive functions in pED, which may unravel the potential neural mechanisms underlying the cognitive impairments of pED patients.

Protective Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment in MK801-Induced Schizophrenia Model.

BACKGROUND: Cognitive dysfunction is a core feature of schizophrenia that strongly correlates to the patients' difficulties in independent living and occupational functioning. Synaptic dysfunction may result in cognitive and behavioral changes similar to what have been identified in schizophrenia. Shi-Zhen-An-Shen Decoction (SZASD) is the empirical formula of traditional Chinese medicine adopted in treating psychiatric symptoms, especially the cognitive impairment in schizophrenia patients, with proven efficacy in the long term of clinical practice in Beijing Anding Hospital, Capital Medical University. However, the mechanisms of SZASD on the cognitive improvement in schizophrenia is still unclear. Here, we aim to investigate the underlying mechanisms of the impact of SZASD on the cognitive impairment in MK801-induced schizophrenia-like rats. METHODS: Six rat groups (n = 12 per group) were subjected to different treatments for 14 days. All the six groups were injected intraperitoneally with a given volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days for modelling. And the rats in the SZASD-treated groups and the clozapine-treated group were given SZASD (low, middle, and high doses) or clozapine, respectively, by intragastric administration. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19th day for biological analysis. RESULTS: Behavioral tests indicated that SZASD mitigated the aberrant motor activity and improved schizophrenia-like rats' spatial reference memory and sensory gating ability. Furthermore, SZASD significantly increased the expressions of PSD95, BDNF, and synapsin I in the hippocampus of MK801-induced schizophrenia-like rats. CONCLUSIONS: Our findings suggest that SZASD may ameliorate cognitive impairment by restoring the levels of synaptic proteins in the hippocampus.

The altered intrinsic functional connectivity after acupuncture at shenmen (HT7) in acute sleep deprivation.

Introduction: Accumulating evidence has shown that acupuncture could significantly improve the sleep quality and cognitive function of individuals suffering from insufficient sleep. Numerous animal studies have confirmed the effects and mechanisms of acupuncture on acute sleep deprivation (SD). However, the role of acupuncture on individuals after acute SD remains unclear. Methods: In the current study, we recruited 30 healthy subjects with regular sleep. All subjects received resting-state fMRI scans during the rested wakefulness (RW) state and after 24 h of total SD. The scan after 24 h of total SD included two resting-state fMRI sessions before and after needling at Shenmen (HT7). Both edge-based and large-scale network FCs were calculated. Results: The edge-based results showed the suprathreshold edges with abnormal between-network FC involving all paired networks except somatosensory motor network (SMN)-SCN between the SD and RW state, while both decreased and increased between-network FC of edges involving all paired networks except frontoparietal network (FPN)-subcortical network (SCN) between before and after acupuncture at HT7. Compared with the RW state, the large-scale brain network results showed decreased between-network FC in SMN-Default Mode Network (DMN), SMN-FPN, and SMN-ventral attention network (VAN), and increased between-network FC in Dorsal Attention Network (DAN)-VAN, DAN-SMN between the RW state and after 24 h of total SD. After acupuncture at HT7, the large-scale brain network results showed decreased between-network FC in DAN-VAN and increased between-network FC in SMN-VAN. Conclusion: Acupuncture could widely modulate extensive brain networks and reverse the specific between-network FC. The altered FC after acupuncture at HT7 may provide new evidence to interpret neuroimaging mechanisms of the acupuncture effect on acute SD.

Attention Performance Correlated With White Matter Structural Brain Networks in Shift Work Disorder.

Neuroimaging studies have revealed that shift work disorder (SWD) affected the functional connectivity in specific brain regions and networks. However, topological disruptions in the structural connectivity of the white matter (WM) networks associated with attention function remain poorly understood. In the current study, we recruited 33 patients with SWD and 29 matched healthy subjects. The attention network test (ANT) was employed to investigate the efficiency of alerting, orienting, and executive control networks. The diffusion tensor imaging (DTI) tractography was used to construct the WM structural networks. The graph theory analysis was applied to detect the alterations of topological properties of structural networks. Our results showed lower alerting effect and higher executive effect for patients with SWD. Using the link-based analysis, 15 altered connectivity matrices (lower fiber numbers) were found between the two groups. Meanwhile, the graph theoretical analysis showed that the global efficiency and characteristic path length within SWD patients declined in contrast with the healthy controls. Furthermore, a significantly negative correlation was found between the executive effect and global network efficiency. Our findings provide the new insights into the fundamental architecture of interregional structural connectivity underlying attention deficits in SWD, which may be a potential biomarker for SWD.