scholarly journals Cytokines and schizophrenia revisited: a two-sample multi-marker Mendelian randomization approach

2019 ◽  
Author(s):  
Hongyan Ren ◽  
Yajing Meng ◽  
Yamin Zhang ◽  
Qiang Wang ◽  
Wei Deng ◽  
...  
Keyword(s):  
Brain Structure ◽  
Mendelian Randomization ◽  
Gray Matter Volume ◽  
Causal Link ◽  
Structure And Function ◽  
Underlying Structure ◽  
Level Data ◽  
Brain Structure And Function ◽  
And Function ◽  
Immune Changes

AbstractBackgroundSchizophrenia is a complex mental disorder with recent evidence suggesting a critical immune component underpinning its pathophysiology. Two-sample Mendelian randomization (MR) provided an opportunity to probe the immune changes in schizophrenia by harnessing the increasing availability of summary-level data from large GWAS consortia.ObjectiveTo map the extensive immune response of schizophrenia in terms of cytokines/chemokines and to explore the effect of cytokines induced by schizophrenia (SCZ-induced cytokines) on the brain structure and functionSources and methodsUsing the summary-level data generated from GWAS of schizophrenia, cytokines in the peripheral blood and imaging-derived phenotypes (IDPs), we performed two rounds of two-sample MR analysis; the identified cytokines from first round of analysis (schizophrenia => cytokines) were modeled for its underlying structure and subsequent clustering analysis further grouped SCZ-induced cytokines based on their genetic similarities. The multi-phenotype summary statistics of each cytokine module were then used as instrumental variables (IVs) for the second round of MR analysis to detect their effect on brain structure and function.ResultsThe first round of MR analysis identified nine cytokines, the highlight of which includes IL18 (OR = 1.292, P = 8.37 × 10−42) and TNFa (OR = 0.721, P = 7.33 × 10−6), to be causally associated with schizophrenia. These SCZ-induced cytokines could be clustered into three modules. The second round of MR analysis (cytokine module => IDPs) indicated that module B (SCGFb-IP10-CTACK-IL6) significantly increased the level of IDPs including IDP_T1_SIENAX_peripheral_grey_normalised_volume (β = 0.0453, P = 4.40×1010), IDP_dMRI_TBSS_MD_Posterior_corona_radiata_R (β= 0.0584, P = 8.89× 10−16) and IDP_dMRI_TBSS_MD_Cingulum_hippocampus_R (β = 0.0563, P = 9.88× 10−15), with module C (IL18-GROa-TNFa) increasing the level of IDP_dMRI_TBSS_L2_Posterior_thalamic_radiation_R (β= 0.0341, P = 2.67× 10−6).ConclusionOur study, for the first time, mapped the causal link from schizophrenia to the comprehensive immune responses, and the findings suggest immune networks play a role in pathophysiology of schizophrenia by mediating the deviations of total gray matter volume and white matter fibers possibly in the mesolimbic system.

scholarly journals Daily Morning Blue Light Therapy for Post-mTBI Sleep Disruption: Effects on Brain Structure and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Adam C. Raikes ◽  
Natalie S. Dailey ◽  
Brittany Forbeck ◽  
Anna Alkozei ◽  
William D. S. Killgore
Keyword(s):  
Functional Connectivity ◽  
Brain Structure ◽  
Daytime Sleepiness ◽  
Gray Matter Volume ◽  
Light Therapy ◽  
Structure And Function ◽  
Sleep Disruption ◽  
Matter Volume ◽  
Brain Structure And Function ◽  
And Function

Background: Mild traumatic brain injuries (mTBIs) are associated with novel or worsened sleep disruption. Several studies indicate that daily morning blue light therapy (BLT) is effective for reducing post-mTBI daytime sleepiness and fatigue. Studies demonstrating changes in brain structure and function following BLT are limited. The present study's purpose is to identify the effect of daily morning BLT on brain structure and functional connectivity and the association between these changes and self-reported change in post-mTBI daytime sleepiness.Methods: A total of 62 individuals recovering from a mTBI were recruited from two US cities to participate in a double-blind placebo-controlled trial. Eligible individuals were randomly assigned to undergo 6 weeks of 30 min daily morning blue or placebo amber light therapy (ALT). Prior to and following treatment all individuals completed a comprehensive battery that included the Epworth Sleepiness Scale as a measure of self-reported daytime sleepiness. All individuals underwent a multimodal neuroimaging battery that included anatomical and resting-state functional magnetic resonance imaging. Atlas-based regional change in gray matter volume (GMV) and region-to-region functional connectivity from baseline to post-treatment were the primary endpoints for this study.Results: After adjusting for pre-treatment GMV, individuals receiving BLT had greater GMV than those receiving amber light in 15 regions of interest, including the right thalamus and bilateral prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with greater GMV in 74 ROIs, covering many of the same general regions. Likewise, BLT was associated with increased functional connectivity between the thalamus and both prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with increased functional connectivity between attention and cognitive control networks as well as decreased connectivity between visual, motor, and attention networks (all FDR corrected p < 0.05).Conclusions: Following daily morning BLT, moderate to large increases in both gray matter volume and functional connectivity were observed in areas and networks previously associated with both sleep regulation and daytime cognitive function, alertness, and attention. Additionally, these findings were associated with improvements in self-reported daytime sleepiness. Further work is needed to identify the personal characteristics that may selectively identify individuals recovering from a mTBI for whom BLT may be optimally beneficial.

scholarly journals The gut microbiome is associated with brain structure and function in schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shijia Li ◽  
Jie Song ◽  
Pengfei Ke ◽  
Lingyin Kong ◽  
Bingye Lei ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Brain Structure ◽  
Gray Matter Volume ◽  
Low Frequency ◽  
Alpha Diversity ◽  
Brain Regions ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
The Right ◽  
And Function

AbstractThe effect of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we used 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZ) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was significantly higher in SZ patients than in NCs. Additionally, the analysis of MRI data revealed that several brain regions showed significantly lower gray matter volume (GMV) and regional homogeneity (ReHo) but significantly higher amplitude of low-frequency fluctuation in SZ patients than in NCs. Moreover, the alpha diversity of the gut microbiota showed a strong linear relationship with the values of both GMV and ReHo. In SZ patients, the ReHo indexes in the right STC (r = − 0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = − 0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = − 0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with the abundance of the genus Roseburia. Our results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function. This study provides insights into the underlying neuropathology of SZ.

scholarly journals Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chia-Chun Hung ◽  
Yi-Hsuan Liu ◽  
Chu-Chung Huang ◽  
Cheng-Ying Chou ◽  
Chun-Ming Chen ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Gray Matter ◽  
Brain Structure ◽  
Functional Organization ◽  
Gray Matter Volume ◽  
Structure And Function ◽  
Control Group ◽  
Matter Volume ◽  
Brain Structure And Function ◽  
And Function

Abstract Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

The Gut Microbiome Was Associated With Brain Structure and Function in Schizophrenia

2021 ◽  
Author(s):  
Shijia Li ◽  
Jie Song ◽  
Pengfei Ke ◽  
Lingyin Kong ◽  
Bingye Lei ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Brain Structure ◽  
Gray Matter Volume ◽  
Low Frequency ◽  
Alpha Diversity ◽  
Brain Regions ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
The Right ◽  
And Function

Abstract The effects of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, our knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we leveraged 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZs) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was increased in SZs compared to NCs. Additionally, the MRI results revealed that several brain regions showed lower gray matter volume (GMV) and regional homogeneity (ReHo), but increased amplitude of low-frequency fluctuation (ALFF) in SZs than in NCs. Statistical analyses were performed to explore the associations between microbial shifts and brain structure and function. Alpha diversity of gut microbiota showed a strong linear relationship with GMV and ReHo. Moreover, we found that lower ReHo indexes in the right STC (r = -0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = -0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = -0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with a lower abundance of the genus Roseburia. This study suggests that the potential role of the gut microbiome in schizophrenia (SZ) is related to the alteration of brain structure and function, suggesting a new direction for studying the pathology of SZ.

scholarly journals The genetics of circulating BDNF: towards understanding the role of BDNF in brain structure and function in middle and old ages

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Shuo Li ◽  
Galit Weinstein ◽  
Habil Zare ◽  
Alexander Teumer ◽  
Uwe Völker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Polymorphism ◽  
Brain Structure ◽  
Mendelian Randomization ◽  
Structure And Function ◽  
Bdnf Gene ◽  
Brain Structure And Function ◽  
And Function

Abstract Brain-derived neurotrophic factor (BDNF) plays an important role in brain development and function. Substantial amounts of BDNF are present in peripheral blood, and may serve as biomarkers for Alzheimer’s disease incidence as well as targets for intervention to reduce Alzheimer’s disease risk. With the exception of the genetic polymorphism in the BDNF gene, Val66Met, which has been extensively studied with regard to neurodegenerative diseases, the genetic variation that influences circulating BDNF levels is unknown. We aimed to explore the genetic determinants of circulating BDNF levels in order to clarify its mechanistic involvement in brain structure and function and Alzheimer’s disease pathophysiology in middle-aged and old adults. Thus, we conducted a meta-analysis of genome-wide association study of circulating BDNF in 11 785 middle- and old-aged individuals of European ancestry from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES), the Framingham Heart Study (FHS), the Rotterdam Study and the Study of Health in Pomerania (SHIP-Trend). Furthermore, we performed functional annotation analysis and related the genetic polymorphism influencing circulating BDNF to common Alzheimer’s disease pathologies from brain autopsies. Mendelian randomization was conducted to examine the possible causal role of circulating BDNF levels with various phenotypes including cognitive function, stroke, diabetes, cardiovascular disease, physical activity and diet patterns. Gene interaction networks analysis was also performed. The estimated heritability of BDNF levels was 30% (standard error = 0.0246, P-value = 4 × 10−48). We identified seven novel independent loci mapped near the BDNF gene and in BRD3, CSRNP1, KDELC2, RUNX1 (two single-nucleotide polymorphisms) and BDNF-AS. The expression of BDNF was associated with neurofibrillary tangles in brain tissues from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP). Seven additional genes (ACAT1, ATM, NPAT, WDR48, TTC21A, SCN114 and COX7B) were identified through expression and protein quantitative trait loci analyses. Mendelian randomization analyses indicated a potential causal role of BDNF in cardioembolism. Lastly, Ingenuity Pathway Analysis placed circulating BDNF levels in four major networks. Our study provides novel insights into genes and molecular pathways associated with circulating BDNF levels and highlights the possible involvement of plaque instability as an underlying mechanism linking BDNF with brain neurodegeneration. These findings provide a foundation for a better understanding of BDNF regulation and function in the context of brain aging and neurodegenerative pathophysiology.

scholarly journals Sequence Variation Associated with SLC12A5 Gene Expression Is Linked to Brain Structure and Function in Healthy Adults

2019 ◽  
Vol 29 (11) ◽  
pp. 4654-4661 ◽  
Author(s):  
Michael D Gregory ◽  
J Shane Kippenhan ◽  
Joseph H Callicott ◽  
Daniel Y Rubinstein ◽  
Venkata S Mattay ◽  
...  
Keyword(s):  
Working Memory ◽  
Brain Structure ◽  
Gray Matter Volume ◽  
Memory Task ◽  
Structural Mri ◽  
Structure And Function ◽  
Mmp9 Expression ◽  
Dorsolateral Prefrontal ◽  
Brain Structure And Function ◽  
And Function

Abstract A single-nucleotide polymorphism in the promoter region of the Matrix Metalloproteinase-9 (MMP9) gene, rs3918242, has been shown to affect MMP9 expression in macrophages and was associated with schizophrenia by two independent groups. However, rs3918242's effects on MMP9 expression were not replicable in cell lines or brain tissue. Additionally, publically available data indicate that rs3918242 genotype is related not to MMP9 expression, but rather to expression of SLC12A5, a nearby gene coding for a K+/Cl- cotransporter, whose expression has also been related to schizophrenia. Here, we studied brain structure and function in healthy participants stratified by rs3918242 genotype using structural MRI (N = 298), functional MRI during an N-back working memory task (N = 554), and magnetoencephalography (MEG) during the same task (N = 190). We found rs3918242 was associated with gray matter volume (GMV) in the insula and dorsolateral prefrontal cortex bilaterally, closely replicated in discovery and replication samples; and with inferior parietal lobule (IPL) GMV when the samples were meta-analytically combined. Additionally, using both fMRI and MEG, rs3918242 was associated with right IPL working memory-related activation, replicated in two cohorts and across imaging modalities. These convergent results provide further impetus for examinations of the relationship of SLC12A5 with brain structure and function in neuropsychiatric disease.

Effects Of Exercise-induced Hypohydration On Brain Structure And Function, A MRI Study

2017 ◽  
Vol 49 (5S) ◽  
pp. 824 ◽  
Author(s):  
X. r. Tan ◽  
Ivan C. C. Low ◽  
Mary C. Stephenson ◽  
T. Kok ◽  
Heinrich W. Nolte ◽  
...  
Keyword(s):  
Brain Structure ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
Exercise Induced ◽  
Mri Study ◽  
And Function

Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on Brain Structure and Function: A study at 4T

2011 ◽  
Vol 32 (6) ◽  
pp. 814-822 ◽  
Author(s):  
Linda L. Chao ◽  
Linda Abadjian ◽  
Jennifer Hlavin ◽  
Deiter J. Meyerhoff ◽  
Michael W. Weiner
Keyword(s):  
Brain Structure ◽  
Gulf War ◽  
Structure And Function ◽  
Gulf War Illness ◽  
Low Level ◽  
Brain Structure And Function ◽  
And Function
Sign in / Sign up

Export Citation Format

Share Document