Functional Changes of White Matter Are Related to Human Pain Sensitivity during Sustained Nociception.

Pain is considered an unpleasant perceptual experience associated with actual or potential somatic and visceral harm. Human subjects have different sensitivity to painful stimulation, which may be related to different painful response pattern. Excellent studies using functional magnetic resonance imaging (fMRI) have found the effect of the functional organization of white matter (WM) on the descending pain modulatory system, which suggests that WM function is feasible during pain modulation. In this study, 26 pain sensitive (PS) subjects and 27 pain insensitive (PIS) subjects were recruited based on cold pressor test. Then, all subjects underwent the cold bottle test (CBT) in normal (26 degrees temperature stimulating) and cold (8 degrees temperature stimulating) conditions during fMRI scan, respectively. WM functional networks were obtained using K-means clustering, and the functional connectivity (FC) was assessed among WM networks, as well as gray matter (GM)-WM networks. Through repeated measures ANOVA, decreased FC was observed between the GM-cerebellum network and the WM-superior temporal network, as well as the WM-sensorimotor network in the PS group under the cold condition, while this difference was not found in PIS group. Importantly, the changed FC was positively correlated with the state and trait anxiety scores, respectively. This study highlighted that the WM functional network might play an integral part in pain processing, and an altered FC may be related to the descending pain modulatory system.

Dynamic functional thalamocortical dysconnectivity in schizophrenia correlates to antipsychotics response.

Although many studies have showed abnormal thalamocortical networks in patients with schizophrenia (SCZ), the dynamic functional thalamocortical connectivity of individuals with SCZ and the effect of antipsychotics on this connectivity have not been investigated. Drug-naïve first-episode individuals with SCZ and healthy controls were recruited. Patients were treated with risperidone for 12 weeks. Resting-state functional magnetic resonance imaging was acquired at baseline and week 12. We identified six functional thalamic subdivisions. The sliding window strategy was used to determine the dynamic functional connectivity (dFC) of each functional thalamic subdivision. Individuals with SCZ displayed decreased or increased dFC variance in different thalamic subdivisions. The baseline dFC between ventral posterior-lateral (VPL) portions and right dorsolateral superior frontal gyrus (rdSFG) correlated with psychotic symptoms. The dFC variance between VPL and right medial orbital superior frontal gyrus (rmoSFG) or rdSFG decreased after 12-week risperidone treatment. The decreased dFC variance between VPL and rmoSFG correlated with the reduction of PANSS scores. Interestingly, the dFC between VPL and rmoSFG or rdSFG decreased in responders. The dFC variance change of VPL and the averaged whole brain signal correlated with the risperidone efficacy. Our study demonstrates abnormal variability in thalamocortical dFC may be implicated in psychopathological symptoms and risperidone response in individuals with schizophrenia, suggesting that thalamocortical dFC variance may be correlated to the efficacy of antipsychotic treatment.Registration: ClinicalTrials.gov Identifier: NCT00435370. https://www.clinicaltrials.gov/ct2/show/NCT00435370?term=NCT00435370&draw=2&rank=1.

Sex differences in factors influencing hospital-acquired pneumonia in schizophrenia patients receiving modified electroconvulsive therapy.

Background: Sex differences may be presented in the clinical features or symptoms of schizophrenia patients but also affect the occurrence of hospital-acquired pneumonia (HAP). Modified electroconvulsive therapy (mECT) is a common treatment method for schizophrenia, used in combination with antipsychotics. This retrospective research explores the sex difference in HAP affecting patients with schizophrenia who have received mECT treatment during hospitalization. Methods: We included schizophrenia inpatients treated with mECT and antipsychotics between January 2015 and April 2022. Blood-related and demographic data collected on admission were analyzed. Influencing factors of HAP in male and female groups were assessed separately. Results: A total of 951 schizophrenia patients treated with mECT were enrolled in the study, including 375 males and 576 females, of which 62 patients experienced HAP during hospitalization. The risk period of HAP in these patients was found to be the first day after each mECT treatment and the first three sessions of mECT treatment. Statistically significant differences in the incidence of HAP were identified in male vs. female groups, with an incidence in men about 2.3 times higher than that in women (P < 0.001). Lower total cholesterol (Z = -2.147, P = 0.032) and the use of anti-parkinsonian drugs (χ2 = 17.973, P < 0.001) were found to be independent risk factors of HAP in male patients, while lower lymphocyte count (Z = -2.408, P = 0.016), hypertension (χ2 = 9.096, P = 0.003), and use of sedative-hypnotic drugs (χ2 = 13.636, P < 0.001) were identified in female patients. Conclusion: Influencing factors of HAP in schizophrenia patients treated with mECT have gender differences. The first day after each mECT treatment and the first three sessions of mECT treatment were identified to have the greatest risk for HAP development. Therefore, it would be imperative to monitor clinical management and medications during this period according to these gender differences.

Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis.

OBJECTIVE: Studies have shown that oxidative stress (OS) is related to the pathophysiology of schizophrenia (SCZ), but whether antipsychotics can induce OS has not been investigated well. Moreover, antipsychotics have differential effects on the OS level modulation, i.e., different types of antipsychotics have different effects on the cellular antioxidants or pro-oxidants. METHODS: We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and investigated the OS indicators including both enzymatic and nonenzymatic markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), vitamin C, etc., of SCZ patients at baseline and follow-up of mono-medication. RESULTS: Twenty studies met the inclusion criteria, with a total of 1162 patients enrolled at baseline, and 1105 patients completed the follow-up. OS markers were changed after a period of antipsychotic treatment in SCZ patients. The GPx activity and MDA level decreased in the whole blood (P<0.05), also the serum MDA level decreased (P<0.05). For the first-episode SCZ patients, the activity of GPx and the level of MDA decreased, while the level of vitamin C increased (all P<0.05). The levels of MDA in patients receiving atypical antipsychotics decreased (P<0.05), while the level of GSH in patients with typical antipsychotics decreased (P=0.05). CONCLUSION: Antipsychotic medication may cause changes in the levels of OS markers in different blood samples of SCZ patients. However, the available studies might not be sufficient to reveal the underlying facts accurately due to the poor quality of experimental designs in the published literature.

Vascular feature as a modulator of the aging brain.

The cerebral functional reorganization and declined cognitive function of aging might associate with altered vascular features. Here, we explored the altered cerebral hierarchical functional network of 2 conditions (task-free and naturalistic stimuli) in older adults and its relationship with vascular features (systemic microvascular and perfusion features, measured by magnetic resonance imaging) and behavior. Using cerebral gradient analysis, we found that compressive gradient of resting-state mainly located on the primary sensory-motor system and transmodal regions in aging, and further compress in these regions under the continuous naturalistic stimuli. Combining cerebral functional gradient, vascular features, and cognitive performance, the more compressive gradient in the resting-state, the worse vascular state, the lower cognitive function in older adults. Further modulation analysis demonstrated that both vascular features can regulate the relationship between gradient scores in the insula and behavior. Interestingly, systemic microvascular oxygenation also can modulate the relationship between cerebral gradient and cerebral perfusion. Furthermore, the less alteration of the compressive gradient with naturalistic stimuli came with lower cognitive function. Our findings demonstrated that the altered cerebral hierarchical functional structure in aging was linked with changed vascular features and behavior, offering a new framework for studying the physiological mechanism of functional connectivity in aging.

Non-antipsychotic medicines and modified electroconvulsive therapy are risk factors for hospital-acquired pneumonia in schizophrenia patients.

Background: Hospital-acquired pneumonia (HAP) has a significant and detrimental impact on schizophrenia patients. Non-antipsychotic medicines and modified electroconvulsive therapy (MECT) are frequently used in conjunction with antipsychotics to treat schizophrenia. Whether non-antipsychotic medicines or MECT are risk factors for HAP in schizophrenia treated with antipsychotics is still unknown. Methods: Patients with schizophrenia who were admitted to the Fourth People's Hospital of Chengdu between January 2015 and April 2022 were included in this retrospective cohort study. Individuals with HAP were 1:1 matched to individuals without HAP (non-HAP) using propensity score matching (PSM). The risk factors for HAP were analyzed by comparing the two groups. Results: A total of 7,085 schizophrenia patients were included in this study, with a mean age of 39.77 ± 14.45 years. 193 patients developed HAP on an average of 22.26 ± 21.68 days after admission with an incidence of 2.73%. After 1:1 PSM, 192 patients from each group (HAP and non-HAP) were included. The HAP group had significantly more patients with MECT and taking benzodiazepines, antidepressants, mood stabilizers, and anti-parkinsonians both before and after PSM by Bonferroni correction (P < 0.001). Multivariate logistic regression analysis showed that, combined with antipsychotics, non-antipsychotic medicines including benzodiazepines (OR = 3.13, 95%CI = 1.95-5.03, P < 0.001), mood stabilizers (OR =3.33, 95%CI =1.79-6.20, P < 0.001) and MECT (OR =2.58, 95%CI =1.49-4.46, P = 0.001) were associated with a significantly increased incidence of HAP. Conclusion: The incidence of HAP in schizophrenia patients in our cohort was 2.73%. MECT and non-antipsychotic medicines, including benzodiazepines and mood stabilizers were risk factors for HAP in schizophrenia patients treated with antipsychotics.

Function-structure coupling: White matter functional magnetic resonance imaging hyper-activation associates with structural integrity reductions in schizophrenia.

White matter (WM) microstructure deficit may be an underlying factor in the brain dysconnectivity hypothesis of schizophrenia using diffusion tensor imaging (DTI). However, WM dysfunction is unclear in schizophrenia. This study aimed to investigate the association between structural deficits and functional disturbances in major WM tracts in schizophrenia. Using functional magnetic resonance imaging (fMRI) and DTI, we developed the skeleton-based WM functional analysis, which could achieve voxel-wise function-structure coupling by projecting the fMRI signals onto a skeleton in WM. We measured the fractional anisotropy (FA) and WM low-frequency oscillation (LFO) and their couplings in 93 schizophrenia patients and 122 healthy controls (HCs). An independent open database (62 schizophrenia patients and 71 HCs) was used to test the reproducibility. Finally, associations between WM LFO and five behaviour assessment categories (cognition, emotion, motor, personality and sensory) were examined. This study revealed a reversed pattern of structure and function in frontotemporal tracts, as follows. (a) WM hyper-LFO was associated with reduced FA in schizophrenia. (b) The function-structure association was positive in HCs but negative in schizophrenia patients. Furthermore, function-structure dissociation was exacerbated by long illness duration and severe negative symptoms. (c) WM activations were significantly related to cognition and emotion. This study indicated function-structure dys-coupling, with higher LFO and reduced structural integration in frontotemporal WM, which may reflect a potential mechanism in WM neuropathologic processing of schizophrenia.