Abstract
Past work on relatively small, single-site studies using regional volumetry, and more recently machine learning methods, has shown that widespread structural brain abnormalities are ...prominent in schizophrenia. However, to be clinically useful, structural imaging biomarkers must integrate high-dimensional data and provide reproducible results across clinical populations and on an individual person basis. Using advanced multi-variate analysis tools and pooled data from case–control imaging studies conducted at 5 sites (941 adult participants, including 440 patients with schizophrenia), a neuroanatomical signature of patients with schizophrenia was found, and its robustness and reproducibility across sites, populations, and scanners, was established for single-patient classification. Analyses were conducted at multiple scales, including regional volumes, voxelwise measures, and complex distributed patterns. Single-subject classification was tested for single-site, pooled-site, and leave-site-out generalizability. Regional and voxelwise analyses revealed a pattern of widespread reduced regional gray matter volume, particularly in the medial prefrontal, temporolimbic and peri-Sylvian cortex, along with ventricular and pallidum enlargement. Multivariate classification using pooled data achieved a cross-validated prediction accuracy of 76% (AUC = 0.84). Critically, the leave-site-out validation of the detected schizophrenia signature showed accuracy/AUC range of 72–77%/0.73–0.91, suggesting a robust generalizability across sites and patient cohorts. Finally, individualized patient classifications displayed significant correlations with clinical measures of negative, but not positive, symptoms. Taken together, these results emphasize the potential for structural neuroimaging data to provide a robust and reproducible imaging signature of schizophrenia. A web-accessible portal is offered to allow the community to obtain individualized classifications of magnetic resonance imaging scans using the methods described herein.
Schizophrenia is a serious neuropsychiatric disorder, yet a clear pathophysiology has not been identified. To date, neither the objective biomarkers for diagnosis nor specific medications for the ...treatment of schizophrenia are clinically satisfactory. It is well accepted that lipids are essential to maintain the normal structure and function of neurons in the brain and that abnormalities in neuronal lipids are associated with abnormal neurodevelopment in schizophrenia. However, lipids and lipid-like molecules have been largely unexplored in contrast to proteins and their genes in schizophrenia. Compared with the gene- and protein-centric approaches, lipidomics is a recently emerged and rapidly evolving research field with particular importance for the study of neuropsychiatric disorders such as schizophrenia, in which even subtle aberrant alterations in the lipid composition and concentration of the neurons may disrupt brain functioning. In this review, we aimed to highlight the lipidomics of the brain, retina, and biofluids in both human and animal studies, discuss aberrant lipid alterations in correlation with schizophrenia, and propose future directions from the biological landscape towards potential clinical applications in schizophrenia. Recent studies are in support of the concept that aberrations in some lipid species e.g. phospholipids, polyunsaturated fatty acids (PUFAs) lead to structural alterations and, in turn, impairments in the biological function of membrane-bound proteins, the disruption of cell signaling molecule accessibility, and the dysfunction of neurotransmitter systems. In addition, abnormal lipidome alterations in biofluids are linked to schizophrenia, and thus they hold promise in the discovery of biomarkers for the diagnosis of schizophrenia.
•The first study to identify genes associated with voxel-mirrored homotopic connectivity (VMHC) alterations in patients with schizophrenia using the transcription-neuroimaging association analysis ...approach.•This study determined the biological functions of the identified genes, as well as the cell types, brain regions and developmental stages in which they were enriched.•We also found cognitive processes related to VMHC alterations in schizophrenia.•The findings offer novel insights into the genetic mechanisms of schizophrenia-related VMHC alterations.
It has been revealed that abnormal voxel-mirrored homotopic connectivity (VMHC) is present in patients with schizophrenia, yet there are inconsistencies in the relevant findings. Moreover, little is known about their association with brain gene expression profiles. In this study, transcription-neuroimaging association analyses using gene expression data from Allen Human Brain Atlas and case-control VMHC differences from both the discovery (meta-analysis, including 9 studies with a total of 386 patients and 357 controls) and replication (separate group-level comparisons within two datasets, including a total of 258 patients and 287 controls) phases were performed to identify genes associated with VMHC alterations. Enrichment analyses were conducted to characterize the biological functions and specific expression of identified genes, and Neurosynth decoding analysis was performed to examine the correlation between cognitive-related processes and VMHC alterations in schizophrenia. In the discovery and replication phases, patients with schizophrenia exhibited consistent VMHC changes compared to controls, which were correlated with a series of cognitive-related processes; meta-regression analysis revealed that illness duration was negatively correlated with VMHC abnormalities in the cerebellum and postcentral/precentral gyrus. The abnormal VMHC patterns were stably correlated with 1287 genes enriched for fundamental biological processes like regulation of cell communication, nervous system development, and cell communication. In addition, these genes were overexpressed in astrocytes and immune cells, enriched in extensive cortical regions and wide developmental time windows. The present findings may contribute to a more comprehensive understanding of the molecular mechanisms underlying VMHC alterations in patients with schizophrenia.
Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are ...growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.
Widespread white matter (WM) abnormalities have been found in patients with schizophrenia. Corpus callosum (CC) is the key area that connects the left and right brain hemispheres. However, the ...results of studies considering different subregions of the CC as regions of interest in patients with schizophrenia have been inconsistent. To obtain a more consistent evaluation of the diffusion characteristics change of the corpus callosum (CC) related to schizophrenia. A meta-analysis involving fractional anisotropy (FA) values in the CC of 729 schizophrenic subjects and 682 healthy controls from 22 studies was conducted. Overall FA values in the CC of the schizophrenic group were less than that of the healthy control group weighted mean difference (WMD) = -0.021,P< 0.001. So were the FA values in the genus region (WMD = -0.019, P< 0.001) and the splenium region (WMD = -0.020, P< 0.001) of the CC respectively. The FA reduction was also significant in subjects with chronic schizophrenia (WMD = -0.032, P< 0.001) and first-episode schizophrenia (WMD = -0.014, P = 0.001). In present study, we demonstrated an overall FA decrease in the CC of schizophrenic patients. In the two subgroup analyses of the genu vs splenium region and chronic vs first-episode schizophrenia, the decrease of all groups was significant. Further studies with more homogenous populations and standardized DTI protocols are needed to confirm and extend these findings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Depression is related to recurrence of atrial fibrillation after catheter ablation.•The association is independent of atrial fibrillation type and follow-up duration.•The association is independent ...of conventional factors of left atrial dimension.
: The influence of depression on the recurrence of atrial fibrillation (AF) after catheter ablation remains unclear. We performed a meta-analysis to evaluate the association between depression and AF recurrence after catheter ablation.
: Cohort studies that evaluated depression at baseline and correlated depression with AF recurrence after catheter ablation were identified by searching the PubMed and Embase databases. Heterogeneity was determined using the Cochrane's Q test and calculating the I2 statistic. A random-effect model was applied to incorporate the potential influence of heterogeneity.
: Our analysis included seven cohort studies with 1,070 AF patients who underwent catheter ablation by circumferential pulmonary vein isolation. No significant heterogeneity was detected among the included studies (p for Cochrane's Q test = 0.20, I2 = 29%). Pooled results showed that depression before procedure was independently associated with increased risk of AF recurrence after catheter ablation (adjusted relative risk RR: 2.24, 95% confidence interval CI: 1.75 - 2.88, p < 0.001). Sensitivity analyses, conducted by omitting one study at a time, retrieved similar results (RR: 2.06 - 2.53, p all < 0.05). Predefined subgroup analyses showed that the association between depression and AF recurrence after catheter ablation was consistent regardless of the study characteristics, including study location, study design, patient number, type of AF, follow-up duration, adjustment of left atrial dimension, and quality score.
: This analysis included a limited number of studies and various instruments applied to measure depression.
: Depression is an independent risk factor of AF recurrence after catheter ablation.
Background/Aims: Gastric cancer (GC) is an important health problem. Classification based on molecular subtypes may help to determine the prognosis of patients with GC. Tumor invasion and metastasis ...are important factors affecting the prognosis of cancer. We aimed to identify genes related to tumor invasion and metastasis, which may serve as indicators of good GC prognosis. Methods: Tumor tissues and adjacent normal tissues were collected from 105 patients with primary GC who were treated by undergoing radical surgery. Samples were used for tissue microarray analysis. Identified genes with altered expression were further analyzed using the Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression levels of THBS2, COL1A2 and SPP1 were analyzed by RT-PCR, western blot and immunohistochemistry. The overall survival curves of patients with high and low expression of each gene of interest were plotted and compared. Results: Forty-three genes were identified. THBS2, COL1A2 and SPP1 were selected for further analysis. Altered expression levels of THBS2, COL1A2 and SPP1 in tumor tissues were confirmed. Patients with low THBS2 expression had a better prognosis; the expression of COL1A2 and SPP1 might not affect the prognosis of patients with GC. Conclusion: THBS2, but not COL1A2 and SPP1, may serve as an indicator of GC prognosis.
•Connections are established between antipsychotics and sudden cardiac death (SCD).•Prediction and management of SCD in users of antipsychotics are challenging.•The risk for SCD in users of ...antipsychotics can be assessed.•New wearable devices may detect early signs of antipsychotic-related SCD.
Sudden cardiac death (SCD) is relatively uncommon, yet it is a deadly consequence of some antipsychotic medications in patients with psychiatric disorders. The widespread concerns about the adverse cardiac effects associated with antipsychotics and their unpredictable nature have led to a restriction on the use of some antipsychotic medications. Recent progress has been made in the identification of important genetic factors that may contribute to the adverse complication of antipsychotic drugs, suggesting that high-risk individuals can be identified prior to initiating therapy. In addition, some high-tech smart wearable medical devices have recently been developed, allowing users to record and analyze the electrocardiogram (ECG) in couple with artificial intelligence (AI) technologies, and notifying of irregular heart rhythms or arrhythmias, a medical condition well documented in most SCD cases. In this literature review, we summarize recent advances in understanding the link between SCD and antipsychotic drug usage, as well as in utilizing wearable medical devices for monitoring of cardiac arrhythmias. New strategies for improving the care of patients receiving antipsychotic medications are proposed. As it is now possible to evaluate the risk of SCD in patients on antipsychotic medications, preventative measures and close monitoring may be used to detect the early signs of adverse cardiac events and SCD.
Auditory verbal hallucinations (AVHs) are experienced by approximately 25% of patients with borderline personality disorder (BPD). Despite the high incidence, the pathological features of AVH in BPD ...remain unclear. This study aimed to investigate whole-brain functional connectivity (FC), as measured by functional connectivity density (FCD), and its relationship with AVH in BPD. 65 pharmacotherapy treatment-naïve female BPD patients (30 with AVH and 35 without AVH), and 35 female healthy controls were investigated. Functional magnetic resonance imaging (fMRI) data were collected to assess whole-brain FC and functional connectivity density mapping (FCDM) was applied to the fMRI data to compute FCD features. Compared to the healthy controls, both BPD groups (BPD–AVH and BPD without AVH) exhibited significantly higher gFCD values in the bilateral prefrontal lobe, bilateral orbital lobule, and bilateral insula, and significantly lower gFCD values in the SMA, right anterior temporal lobule, and the ACC. These altered regions were significantly associated with AVH in the BPD subjects. Moreover, higher gFCD values were observed in the left posterior temporal lobule and posterior frontal lobule. Aberrant alterations also emerged in the left posterior temporal lobule and posterior frontal lobule, mainly in Broca and Wernicke regions. Nevertheless, there was no significant correlation between gFCD values and the severity of AVH as measured by the AVH scores. In summary, we have identified aberrations in the FC and brain metabolism of the aforementioned neural circuits/networks, which may provide new insights into BPD–AVH and facilitate the development of therapeutic approaches for treating AVH in BPD patients.
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