scholarly journals Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

2016 ◽  
Author(s):  
LM Reus ◽  
X Shen ◽  
J Gibson ◽  
E Wigmore ◽  
L Ligthart ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Regions ◽  
Uk Biobank ◽  
Imaging Data ◽  
Brain Volumes ◽  
Polygenic Risk ◽  
Subcortical Brain ◽  
The Impact ◽  
Subcortical Volumes

AbstractMajor depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data compromised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). Our, findings however, indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. In the current study, we found little or no evidence for genetic overlap between major psychiatric disorders and structural brain measures. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.

scholarly journals Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Steluta Grama ◽  
Isabella Willcocks ◽  
John J. Hubert ◽  
Antonio F. Pardiñas ◽  
Sophie E. Legge ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Specific Gene ◽  
Whole Genome ◽  
Uk Biobank ◽  
Abnormal Behaviour ◽  
Brain Volumes ◽  
Polygenic Risk ◽  
Subcortical Brain ◽  
Gene Sets ◽  
The Uk

Abstract Research has shown differences in subcortical brain volumes between participants with schizophrenia and healthy controls. However, none of these differences have been found to associate with schizophrenia polygenic risk. Here, in a large sample (n = 14,701) of unaffected participants from the UK Biobank, we test whether schizophrenia polygenic risk scores (PRS) limited to specific gene-sets predict subcortical brain volumes. We compare associations with schizophrenia PRS at the whole genome level (‘genomic’, including all SNPs associated with the disorder at a p-value threshold < 0.05) with ‘genic’ PRS (based on SNPs in the vicinity of known genes), ‘intergenic’ PRS (based on the remaining SNPs), and genic PRS limited to SNPs within 7 gene-sets previously found to be enriched for genetic association with schizophrenia (‘abnormal behaviour,’ ‘abnormal long-term potentiation,’ ‘abnormal nervous system electrophysiology,’ ‘FMRP targets,’ ‘5HT2C channels,’ ‘CaV2 channels’ and ‘loss-of-function intolerant genes’). We observe a negative association between the ‘abnormal behaviour’ gene-set PRS and volume of the right thalamus that survived correction for multiple testing (ß = −0.031, pFDR = 0.005) and was robust to different schizophrenia PRS p-value thresholds. In contrast, the only association with genomic PRS surviving correction for multiple testing was for right pallidum, which was observed using a schizophrenia PRS p-value threshold < 0.01 (ß = −0.032, p = 0.0003, pFDR = 0.02), but not when using other PRS P-value thresholds. We conclude that schizophrenia PRS limited to functional gene sets may provide a better means of capturing differences in subcortical brain volume than whole genome PRS approaches.

The Relationship Between Isolated Hypertension with Brain Volumes in UK Biobank

2021 ◽  
Author(s):  
Danielle Newby ◽  
Laura Winchester ◽  
William Sproviero ◽  
Marco Fernandes ◽  
Upamanyu Ghose ◽  
...  
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Brain Mri ◽  
Uk Biobank ◽  
Brain Health ◽  
Brain Volumes ◽  
Dementia Risk ◽  
Diastolic Hypertension ◽  
The Impact ◽  
The Relationship

Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertension, such as, isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure or systolic-diastolic hypertension using the largest cohort of healthy individuals. Using the UK Biobank cohort, we carried out a cross-sectional study using 29775 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models adjusted for multiple confounders to compare a variety of global, sub cortical and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic-diastolic hypertension. The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller grey matter but larger white matter microstructures and macrostructures compared to normotensives. However, isolated hypertensives had larger total grey matter and smaller white matter traits when comparing these regions with participants with systolic-diastolic hypertension.These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic-diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.

scholarly journals Associations Between Brain Volumes and Cognitive Tests with Hypertensive Burden in UK Biobank

2021 ◽  
pp. 1-17
Author(s):  
Danielle Newby ◽  
Laura Winchester ◽  
William Sproviero ◽  
Marco Fernandes ◽  
Di Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
White Matter ◽  
Small Sample ◽  
Self Report ◽  
Cognitive Tests ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Brain Volumes ◽  
Multiple Measures ◽  
The Impact

Background: Mid-life hypertension is an established risk factor for cognitive impairment and dementia and related to greater brain atrophy and poorer cognitive performance. Previous studies often have small sample sizes from older populations that lack utilizing multiple measures to define hypertension such as blood pressure, self-report information, and medication use; furthermore, the impact of the duration of hypertension is less extensively studied. Objective: To investigate the relationship between hypertension defined using multiple measures and length of hypertension with brain measure and cognition. Methods: Using participants from the UK Biobank MRI visit with blood pressure measurements (n = 31,513), we examined the cross-sectional relationships between hypertension and duration of hypertension with brain volumes and cognitive tests using generalized linear models adjusted for confounding. Results: Compared with normotensives, hypertensive participants had smaller brain volumes, larger white matter hyperintensities (WMH), and poorer performance on cognitive tests. For total brain, total grey, and hippocampal volumes, those with greatest duration of hypertension had the smallest brain volumes and the largest WMH, ventricular cerebrospinal fluid volumes. For other subcortical and white matter microstructural regions, there was no clear relationship. There were no significant associations between duration of hypertension and cognitive tests. Conclusion: Our results show hypertension is associated with poorer brain and cognitive health however, the impact of duration since diagnosis warrants further investigation. This work adds further insights by using multiple measures defining hypertension and analysis on duration of hypertension which is a substantial advance on prior analyses—particularly those in UK Biobank which present otherwise similar analyses on smaller subsets.

scholarly journals Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank

2020 ◽  
Author(s):  
Xingxing Zhu ◽  
Joey Ward ◽  
Breda Cullen ◽  
Donald M. Lyall ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Cortical Thickness ◽  
Brain Structure ◽  
Anterior Cingulate ◽  
White Matter Integrity ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Matter Volume

AbstractBackgroundAnhedonia is a core symptom of multiple psychiatric disorders and has been associated with changes in brain structure. Genome-wide association studies suggest that anhedonia is heritable with a polygenic architecture but few studies have explored the association between genetic loading for anhedonia - indexed by polygenic risk scores for anhedonia (PRS-anhedonia) - and structural brain imaging phenotypes. We investigated how anhedonia and polygenic risk for anhedonia were associated with brain structure within the UK Biobank cohort.MethodsBrain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness and white matter integrity) were analysed in relation to the self-reported anhedonia phenotype and PRS-anhedonia for 17,492 participants (8,506 males and 8,986 females; mean age = 62.81 years, SD = 7.43), using linear mixed models and including mediation analyses.ResultsState anhedonia was significantly associated with smaller total grey matter volume (GMV), smaller volumes in thalamus and nucleus accumbens; as well as reduced cortical thickness within the paracentral gyrus, the opercular part of inferior frontal gyrus and the rostral anterior cingulate cortex. PRS-anhedonia was associated with reduced total GMV, increased total white matter volume and reduced white matter integrity; in addition to reduced cortical thickness within the parahippocampal cortex, the superior temporal gyrus and the insula cortex.ConclusionsBoth the state anhedonia phenotype and PRS-anhedonia were associated with differences in multiple brain structures/areas, including within reward-related circuits. These differences may represent vulnerability markers for psychopathology across a range of psychiatric disorders.

scholarly journals Retrospective analysis of hemispheric structural network change as a function of location and size of glioma

2020 ◽  
Author(s):  
Shawn D’Souza ◽  
Lisa Hirt ◽  
David R Ormond ◽  
John A Thompson
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Temporal Lobe ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Structural Network ◽  
Tumour Location ◽  
The Impact ◽  
Tractography Data ◽  
Diffusion Tensor Imaging Tractography

Abstract Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.

scholarly journals Relationship Between Verbal Fluency Performance, Fight Exposure, and Subcortical Region Brain Volumes in Professional Fighters

2019 ◽  
Vol 34 (5) ◽  
pp. 735-735
Author(s):  
L Bennett ◽  
C Bernick ◽  
S Banks
Keyword(s):  
Verbal Fluency ◽  
Brain Structures ◽  
Brain Regions ◽  
Health Study ◽  
Semantic Fluency ◽  
Cognitive Changes ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Subcortical Region ◽  
Subcortical Brain Structures

Abstract Purpose Verbal fluency performance has been shown to be sensitive to preclinical cognitive changes in neurodegenerative diseases and may detect early, trauma-related cognitive and volumetric changes amongst professional fighters. Baseline verbal fluency performance and volumes of relevant subcortical brain structures were expected to decline as number of professional fights (NoPF) increased, while controlling for education. Methods Baseline letter and semantic fluency performance, NoPF, and structural brain imaging from 548 active and retired fighters who participated in the Professional Fighters Brain Health Study were considered. ANCOVAs were conducted to assess differences in verbal fluency performance by NOPF, while controlling for years of education. Number of professional fights were stratified into low (0-20 fights), medium (21-40 fights), and high (41 or more fights). Results Semantic fluency performance differed across the three levels of NoPF (F(2, 542)=4.56; p<.02). In addition, significant positive correlations between semantic fluency performance and volumes in the following regions were observed: left thalamus, left putamen, left pallidum, bilateral caudates, bilateral amygdalae, bilateral hippocampi, and bilateral accumbens (all p’s<.05). In contrast, letter fluency performance was not significantly associated with NoPF or volumes of relevant subcortical brain structures (all p’s>.05). Conclusion Semantic fluency may be low-cost, easy-to-administer harbinger of emerging cognitive dysfunction and lower volumes in related subcortical brain regions. Additional assessment of clinical utility is necessary.

scholarly journals Review of Twin and Family Studies on Neuroanatomic Phenotypes and Typical Neurodevelopment

2007 ◽  
Vol 10 (5) ◽  
pp. 683-694 ◽  
Author(s):  
J. Eric Schmitt ◽  
Lisa T. Eyler ◽  
Jay N. Giedd ◽  
William S. Kremen ◽  
Kenneth S. Kendler ◽  
...  
Keyword(s):  
Brain Structure ◽  
Emotional Regulation ◽  
Behavioral Genetics ◽  
Genetic Relationships ◽  
Twin Studies ◽  
Brain Regions ◽  
Phenotypic Variance ◽  
Imaging Data ◽  
Brain Volumes ◽  
Large Brain

AbstractThis article reviews the extant twin studies employing magnetic resonance imaging data (MRI), with an emphasis on studies of populationbased samples. There have been approximately 75 twin reports using MRI, with somewhat under half focusing on typical brain structure. Of these, most are samples of adults. For large brain regions such as lobar volumes, the heritabilities of large brain volumes are consistently high, with genetic factors accounting for at least half of the phenotypic variance. The role of genetics in generating individual differences in the volumes of small brain regions is less clear, mostly due to a dearth of information, but rarely because of disagreement between studies. Multivariate analyses show strong genetic relationships between brain regions. Cortical regions involved in language, executive function, and emotional regulation appear to be more heritable than other areas. Studies of brain shape also show significant, albeit lower, genetic effects on population variance. Finally, there is evidence of significant genetically mediated relationships between intelligence and brain structure. At present, the majority of twin imaging studies are limited by sample sizes small by the standards of behavioral genetics; nevertheless the literature at present represents a pioneering effort in the pursuit of answers to many challenging neurobiological questions.

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