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BMC Medicine Jul 2023Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure and cognitive function, but it remains unclear...
BACKGROUND
Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure and cognitive function, but it remains unclear whether COVID-19 causes brain structural changes and which specific brain regions are affected. Herein, we conducted a Mendelian randomization (MR) study to investigate this causal relationship and to identify specific brain regions vulnerable to COVID-19.
METHODS
Genome-wide association study (GWAS) data for COVID-19 phenotypes (28,900 COVID-19 cases and 3,251,161 controls) were selected as exposures, and GWAS data for brain structural traits (cortical thickness and surface area from 51,665 participants and volume of subcortical structures from 30,717 participants) were selected as outcomes. Inverse-variance weighted method was used as the main estimate method. The weighted median, MR-Egger, MR-PRESSO global test, and Cochran's Q statistic were used to detect heterogeneity and pleiotropy.
RESULTS
The genetically predicted COVID-19 infection phenotype was nominally associated with reduced cortical thickness in the caudal middle frontal gyrus (β = - 0.0044, p = 0.0412). The hospitalized COVID-19 phenotype was nominally associated with reduced cortical thickness in the lateral orbitofrontal gyrus (β = - 0.0049, p = 0.0328) and rostral middle frontal gyrus (β = - 0.0022, p = 0.0032) as well as with reduced cortical surface area of the middle temporal gyrus (β = - 10.8855, p = 0.0266). These causal relationships were also identified in the severe COVID-19 phenotype. Additionally, the severe COVID-19 phenotype was nominally associated with reduced cortical thickness in the cuneus (β = - 0.0024, p = 0.0168); reduced cortical surface area of the pericalcarine (β = - 2.6628, p = 0.0492), superior parietal gyrus (β = - 5.6310, p = 0.0408), and parahippocampal gyrus (β = - 0.1473, p = 0.0297); and reduced volume in the hippocampus (β = - 15.9130, p = 0.0024).
CONCLUSIONS
Our study indicates a suggestively significant association between genetic predisposition to COVID-19 and atrophy in specific functional regions of the human brain. Patients with COVID-19 and cognitive impairment should be actively managed to alleviate neurocognitive symptoms and minimize long-term effects.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; COVID-19; Brain; Cognition
PubMed: 37468885
DOI: 10.1186/s12916-023-02952-1 -
Frontiers in Immunology 2023The brains of COVID-19 patients are affected by the SARS-CoV-2 virus, and these effects may contribute to several COVID-19 sequelae, including cognitive dysfunction... (Review)
Review
The brains of COVID-19 patients are affected by the SARS-CoV-2 virus, and these effects may contribute to several COVID-19 sequelae, including cognitive dysfunction (termed "long COVID" by some researchers). Recent advances concerning the role of neuroinflammation and the consequences for brain function are reviewed in this manuscript. Studies have shown that respiratory SARS-CoV-2 infection in mice and humans is associated with selective microglial reactivity in the white matter, persistently impaired hippocampal neurogenesis, a decrease in the number of oligodendrocytes, and myelin loss. Brain MRI studies have revealed a greater reduction in grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus, associated with a greater reduction in global brain size, in those with SARS-CoV-2 and a greater cognitive decline. COVID-19 can directly infect endothelial cells of the brain, potentially promoting clot formation and stroke; complement C3 seems to play a major role in this process. As compared to controls, the brain tissue of patients who died from COVID-19 have shown a significant increase in the extravasation of fibrinogen, indicating leakage in the blood-brain barrier; furthermore, recent studies have documented the presence of IgG, IgM, C1q, C4d, and C5b-9 deposits in the brain tissue of COVID-19 patients. These data suggest an activation of the classical complement pathway and an immune-mediated injury to the endothelial cells. These findings implicate both the classical and alternative complement pathways, and they indicate that C3b and the C5b-9 terminal complement complex (membrane attack complex, MAC) are acting in concert with neuroinflammatory and immune factors to contribute to the neurological sequelae seen in patients with COVID.
Topics: Humans; Mice; Animals; Complement Membrane Attack Complex; Endothelial Cells; SARS-CoV-2; COVID-19; Brain
PubMed: 37533859
DOI: 10.3389/fimmu.2023.1216457 -
Neuron Feb 2024In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal cortex (EC). Why these initially appear in...
In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal cortex (EC). Why these initially appear in disparate locations is not understood. Using task-based fMRI and multimodal PET imaging, we assess the impact of local AD pathology on network-to-network interactions. We show that AD pathologies flip interactions between the default mode network (DMN) and the medial temporal lobe (MTL) from inhibitory to excitatory. The DMN is hyperexcited with increasing levels of Aβ, which drives hyperexcitability within the MTL and this directed hyperexcitation of the MTL by the DMN predicts the rate of tau accumulation within the EC. Our results support a model whereby Aβ induces disruptions to local excitatory-inhibitory balance in the DMN, driving hyperexcitability in the MTL, leading to tau accumulation. We propose that Aβ-induced disruptions to excitatory-inhibitory balance is a candidate causal route between Aβ and remote EC-tau accumulation.
Topics: Humans; tau Proteins; Default Mode Network; Alzheimer Disease; Amyloid beta-Peptides; Entorhinal Cortex; Magnetic Resonance Imaging; Positron-Emission Tomography
PubMed: 38096815
DOI: 10.1016/j.neuron.2023.11.014 -
Frontiers in Endocrinology 2023Previous studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the...
BACKGROUND
Previous studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the impact of NAFLD on cerebral cortical structure and specific affected brain regions remains unclear. Therefore, we aimed to explore the potential causal relationship between NAFLD and cerebral cortical structure.
METHODS
We conducted a Mendelian randomization (MR) study using genetic predictors of alanine aminotransferase (ALT), NAFLD, and percent liver fat (PLF) and combined them with genome-wide association study (GWAS) summary statistics from the ENIGMA Consortium. Several methods were used to assess the effect of NAFLD on full cortex and specific brain regions, along with sensitivity analyses.
RESULTS
At the global level, PLF nominally decreased SA of full cortex; at the functional level, ALT presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars orbitalis, and TH of pericalcarine cortex. Besides, NAFLD presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars triangularis and TH of pericalcarine cortex, but increased TH of entorhinal cortex, lateral orbitofrontal cortex and temporal pole. Furthermore, PLF presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of cuneus and lingual gyrus, but increased TH of entorhinal cortex.
CONCLUSION
NAFLD is suggestively associated with atrophy in specific functional regions of the human brain.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Mendelian Randomization Analysis; Genome-Wide Association Study; Magnetic Resonance Imaging; Cerebral Cortex
PubMed: 38027213
DOI: 10.3389/fendo.2023.1276576 -
Current Opinion in Psychiatry Nov 2023Bullying is a common adversity affecting many children and adolescents. It has been shown to negatively impact the psychological well being not only of targets of... (Review)
Review
PURPOSE OF REVIEW
Bullying is a common adversity affecting many children and adolescents. It has been shown to negatively impact the psychological well being not only of targets of bullying, but also that of bullying perpetrators and those witnessing bullying. Bullying is linked to depression and poorer mental health and functioning among children and adolescents. Given the high prevalence of bullying among children and adolescents and the negative mental health sequelae of bullying, this is an area of urgent public health concern. This narrative review brings forth recent research findings in this arena, which could help shape public health policies for addressing and preventing bullying.
RECENT FINDINGS
Recent findings demonstrate an association of bullying among children and adolescents with depression, nonsuicidal self-injury, sleep loss, reduced health-related quality of life, poorer rates of graduation from high school and later mental health problems. A recent systematic review also showed an association of peer-victimization among children and adolescents with activation of amygdala, left parahippocampal gyrus and fusiform gyrus, and alterations in other brain areas.
SUMMARY
Evidence indicates that bullying in childhood and adolescence is associated with higher odds of developing mental health problems; therefore, early identification and timely intervention is crucial.
Topics: Child; Humans; Adolescent; Quality of Life; Bullying; Mental Health; Brain; Peer Group
PubMed: 37781982
DOI: 10.1097/YCO.0000000000000900 -
Nature Communications Oct 2023Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic...
Hippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic memory. Supra-theta rhythms of hippocampal CA1 are coordinated by local interactions as well as inputs from the entorhinal cortex (EC) and CA3 inputs. However, theta-nested gamma-band activity in the medial septum (MS) suggests that the MS may control supra-theta CA1 oscillations. To address this, we performed multi-electrode recordings of MS and CA1 activity in rodents and found that MS neuron firing showed strong phase-coupling to theta-nested supra-theta episodes and predicted changes in CA1 beta-to-gamma oscillations on a cycle-by-cycle basis. Unique coupling patterns of anatomically defined MS cell types suggested that indirect MS-to-CA1 pathways via the EC and CA3 mediate distinct CA1 gamma-band oscillations. Optogenetic activation of MS parvalbumin-expressing neurons elicited theta-nested beta-to-gamma oscillations in CA1. Thus, the MS orchestrates hippocampal network activity at multiple temporal scales to mediate memory encoding and retrieval.
Topics: Hippocampus; Neurons; Entorhinal Cortex; Theta Rhythm; Parvalbumins; Action Potentials; CA1 Region, Hippocampal
PubMed: 37816713
DOI: 10.1038/s41467-023-41746-0