Asparagine reduces the risk of schizophrenia: a bidirectional two-sample mendelian randomization study of aspartate, asparagine and schizophrenia.

BACKGROUND: Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. METHODS: This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. RESULTS: No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483-3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987-1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999-1.011, P-value = 0.132). CONCLUSION: This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Concomitant functional impairment and reorganization in the linkage between the cerebellum and default mode network in patients with type 2 diabetes mellitus.

BACKGROUND: Increasing evidence shows that the default mode network (DMN) and cerebellum are prone to structural and functional abnormalities in patients with type 2 diabetes mellitus (T2DM). However, the type of change in the functional connection between the DMN and cerebellum is still unknown. METHODS: In this study, seed-based functional connectivity (FC) analysis was used to examine the intrinsic FC of the cerebellum-DMN between healthy controls (HCs) and T2DM patients. Pearson correlation analysis was used to explore the relationship between clinical variables and changes in FC. RESULTS: Compared with HCs, T2DM patients showed significantly increased FC of the left crus I-left medial superior frontal gyrus, left crus I-right medial superior frontal gyrus, and right crus I-left medial orbitofrontal cortex. Compared with HCs, T2DM patients showed decreased FC of the lobule IX-the right angular gyrus. Moreover, diabetes duration was positively correlated with increased FC of the left crus I-right medial superior frontal gyrus (r=0.438, P=0.007). CONCLUSIONS: Concomitant functional impairment and reorganization in the linkage between the cerebellum and DMN in patients with T2DM may be a biomarker of early brain damage that can help us better understand the pathogenesis of cognitive impairment in T2DM.

Pathological Between-Network Positive Connectivity in Early Type 2 Diabetes Patients Without Cerebral Small Vessel Diseases.

BACKGROUND AND PURPOSE: Previous neuroimaging studies have demonstrated type 2 diabetes (T2D)-related brain structural and functional changes are partly associated with cognitive decline. However, less is known about the underlying mechanisms. Chronic hyperglycemia and microvascular complications are the two of most important risk factors related to cognitive decline in diabetes. Cerebral small vessel diseases (CSVDs), such as those defined by lacunar infarcts, white matter hyperintensities (WMHs) and microhemorrhages, are also associated with an increased risk of cognitive decline and dementia. In this study, we examined brain magnetic resonance imaging (MRI) changes in patients in the early stages of T2D without CSVDs to focus on glucose metabolism factors and to avoid the interference of vascular risk factors on T2D-related brain damage. METHODS: T2D patients with disease durations of less than 5 years and without any signs of CSVDs (n = 34) were compared with healthy control subjects (n = 24). Whole-brain region-based functional connectivity was analyzed with network-based statistics (NBS), and brain surface morphology was examined. In addition, the Montreal Cognitive Assessment (MoCA) was conducted for all subjects. RESULTS: At the whole-brain region-based functional connectivity level, thirty-three functional connectivities were changed in T2D patients relative to those in controls, mostly manifested as pathological between-network positive connectivity and located mainly between the sensory-motor network and auditory network. Some of the connectivities were positively correlated with blood glucose level, insulin resistance, and MoCA scores in the T2D group. The network-level analysis showed between-network hyperconnectivity in T2D patients, but no significant changes in within-network connectivity. In addition, there were no significant differences in MoCA scores or brain morphology measures, including cortical thickness, surface area, mean curvature, and gray/white matter volume, between the two groups. CONCLUSION: The findings indicate that pathological between-network positive connectivity occurs in the early stages of T2D without CSVDs. The abnormal connectivity may indicate that the original balance of mutual antagonistic/cooperative relationships between the networks is broken, which may be a neuroimaging basis for predicting cognitive decline in early T2D patients.

Changes in default mode network connectivity in different glucose metabolism status and diabetes duration.

AIMS/HYPOTHESES: It is now generally accepted that diabetes increases the risk for cognitive impairment, but the precise mechanisms are poorly understood. In recent years, resting-state functional magnetic resonance imaging (rs-fMRI) is increasingly used to investigate the neural basis of cognitive dysfunction in type 2 diabetes (T2D) patients. Alterations in brain functional connectivity may underlie diabetes-related cognitive dysfunction and brain damage. The aim of this study was to investigate the changes in default mode network (DMN) connectivity in different glucose metabolism status and diabetes duration. METHODS: We used a seed-based fMRI analysis to investigate positive and negative DMN connectivity in four groups (39 subjects with normal glucose metabolism [NGM], 23 subjects with impaired glucose metabolism [IGM; i.e., prediabetes], 59 T2D patients with a diabetes duration of <10 years, and 24 T2D patients with a diabetes duration of ≥10 years). RESULTS: Negative DMN connectivity increased and then regressed with deteriorating glucose metabolism status and extending diabetes duration. DMN connectivity showed a significant correlation with diabetes duration. CONCLUSION/INTERPRETATION: This study suggests that DMN connectivity may exhibit distinct patterns in different glucose metabolism status and diabetes duration, providing some potential neuroimaging evidence for early diagnosis and further understanding of the pathophysiological mechanisms of diabetic brain damage.

Investigation of cerebral iron deposition in aged patients with ischemic cerebrovascular disease using susceptibility-weighted imaging.

OBJECTIVE: The aim of this study was to investigate focal iron deposition level in the brain in patients with ischemic cerebrovascular disease and its correlation with cerebral small vessel disease imaging markers. PATIENTS AND METHODS: Seventy-four patients with first-ever transient ischemic attack (median age: 69 years; 30 males and 44 females) and 77 patients with positive ischemic stroke history (median age: 72 years; 43 males and 34 females) were studied retrospectively. On phase image of susceptibility-weighted imaging and regions of interest were manually drawn at the bilateral head of the caudate nucleus, lenticular nucleus (LN), thalamus (TH), frontal white matter, and occipital white matter. The correlation between iron deposition level and the clinical and imaging variables was also investigated. RESULTS: Iron deposition level at LN was significantly higher in patients with previous stroke history. It linearly correlated with the presence and number of cerebral microbleeds (CMBs) but not with white matter hyperintensity and lacunar infarct. Multiple linear regression analysis showed that deep structure CMBs were the most relevant in terms of iron deposition at LN. CONCLUSION: Iron deposition at LN may increase in cases of more severe ischemia in aged patients with transient ischemic attack, and it may be an imaging marker for CMB of ischemic origin.

Contrast-enhanced ultrasound and computerized tomography perfusion imaging of a liver fibrosis-early cirrhosis in dogs.

BACKGROUND AND AIM: To assess liver fibrosis stages in a liver fibrosis-early cirrhosis model in dogs, the clinical efficiency of contrast-enhanced ultrasound (CEUS) and computed tomography (CT) perfusion imaging were compared. METHODS: Hepatic vein arriving time (HVAT), hepatic artery arriving time, and hepatic artery to vein transit time (HA-VTT) were measured on CEUS. Total liver perfusion (TLP), portal vein perfusion (PVP), hepatic artery perfusion, and hepatic perfusion index (HPI) were measured on CT perfusion imaging. Histologic examination of liver specimens of the animals was performed to assess the fibrosis stage. RESULTS: For assessment of liver fibrosis, the area under the receiver operating characteristic curve of CEUS indexes HVAT and HA-VTT were 0.865 and 0.930, respectively; the perfusion CT indexes TLP, PVP, and HPI were 0.797, 0.800, and 0.220, respectively; the serological index hyaluronic acid was 0.793. While for assessment of early cirrhosis, the area under the receiver operating characteristic curve of CEUS indexes HVAT and HA-VTT were 0.915 and 0.948, respectively; the perfusion CT indexes TLP, PVP, and HPI were 0.737, 0.765, and 0.218, respectively; the serological index hyaluronic acid was 0.627. CONCLUSIONS: This study showed that both CEUS and CT perfusion imaging have the potential to be complementary imaging tools in the evaluation of liver fibrosis. While CEUS is the better choice and the index HA-VTT can be considered as non-invasive semi-quantitative indexes for diagnosing liver fibrosis and early cirrhosis.

[Diagnostic value of liver CT for acute necrotizing pancreatitis].

OBJECTIVE: To determine diagnostic value of liver CT for acute necrotizing pancreatitis. METHODS: A total of 130 patients with the acute necrotizing pancreatitis underwent abdominal helical contrast CT scanning, whose pancreatitis was graded and the live CT values were measured. RESULTS: Altogether 111 patients had decreased liver CT value.Twenty-seven patients with decreased liver CT value were in Grade I, 54 in Grade II, 21 in Grade III, and 9 in Grade IV. There was a negative correlation between CT grades of the liver and CT value of acute necrotizing pancreatitis (r = -0.279, P = 0.008). CONCLUSION: The CT value of liver density has diagnostic value in acute necrotizing pancreatitis.