Disturbed hypothalamus-pituitary-adrenal axis function, which leads to excessive and prolonged hypercortisolemia, is a core feature of major depressive disorder (MDD). However, the relationships between depression, brain structure and function, and cortisol levels are unclear. The current study examined the whole-brain functional connectivity pattern of patients with MDD and evaluated the association between functional connectivity and serum cortisol levels in MDD. A total of 93 unmedicated patients with MDD and 139 healthy control subjects underwent resting-state functional magnetic resonance imaging. Voxel-wise whole-brain connectivity was analyzed by using a graph theory approach: functional connectivity strength (FCS). A seed-based resting-state functional connectivity analysis was further performed to investigate abnormal functional connectivity patterns of those regions with changed FCS. Morning blood samples were drawn for cortisol measurements in some subjects (including 53 MDD patients and 30 controls). The MDD patients had a significantly lower FCS in the left posterior lobes of the cerebellum (mainly lobule Crus II) (p < 0.05, TFCE corrected). The seed-based functional connectivity analysis revealed decreased functional connectivity between the left posterior cerebellum and the left medial orbitofrontal cortex (OFC) (p < 0.05, TFCE corrected). Moreover, the functional connectivity between the left posterior cerebellum and the left medial OFC were significantly positively correlated with the serum cortisol levels in MDD patients. Our results suggest that cerebellar dysconnectivity, in particular distributed cerebellar-OFC functional connectivity, may be associated with serum cortisol levels in MDD patients.
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http://dx.doi.org/10.1016/j.jpsychires.2018.08.025 | DOI Listing |
Nat Methods
January 2025
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China.
Background: One of the etiologic components of degenerative spinal illnesses is intervertebral disc degeneration (IVDD), and the accompanying lower back pain is progressively turning into a significant public health problem. Important pathologic characteristics of IVDD include inflammation and acidic microenvironment, albeit it is unclear how these factors contribute to the disease.
Purpose: To clarify the functions of inflammation and the acidic environment in IVDD, identify the critical connections facilitating glycolytic crosstalk and nucleus pulposus cells (NPCs) pyroptosis, and offer novel approaches to IVDD prevention and therapy.
Nat Commun
January 2025
MRC Laboratory of Medical Sciences, London, UK.
Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.
View Article and Find Full Text PDFMethods Enzymol
January 2025
Department of Chemistry, Washington University in St. Louis, MO, United States. Electronic address:
Adenosine-to-inosine (A-to-I) editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a prevalent post-transcriptional modification that is vital for numerous biological functions. Given that this modification impacts global gene expression, RNA localization, and innate cellular immunity, dysregulation of A-to-I editing has unsurprisingly been linked to a variety of cancers and other diseases. However, our current understanding of the underpinning mechanisms that connect dysregulated A-to-I editing and disease processes remains limited.
View Article and Find Full Text PDFJ Adv Res
January 2025
Proteomics and Metabolomics Unit, Basic Research Department, Children's Cancer Hospital, 57357 Cairo, (CCHE-57357), Egypt; Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University, 41522 Ismailia, Egypt. Electronic address:
Introduction: Gut microbiota alterations have been implicated in Autism Spectrum Disorder (ASD), yet the mechanisms linking these changes to ASD pathophysiology remain unclear.
Objectives: This study utilized a multi-omics approach to uncover mechanisms linking gut microbiota to ASD by examining microbial diversity, bacterial metaproteins, associated metabolic pathways and host proteome.
Methods: The gut microbiota of 30 children with severe ASD and 30 healthy controls was analyzed.
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