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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xingxing Zhu ◽  
Joey Ward ◽  
Breda Cullen ◽  
Donald M. Lyall ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Association Studies ◽  
Anterior Cingulate ◽  
White Matter Integrity ◽  
Grey Matter Volume ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Matter Volume

AbstractAnhedonia is a core symptom of multiple psychiatric disorders and has been associated with alterations 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. Here, we investigated how anhedonia and PRS-anhedonia were associated with brain structure within the UK Biobank cohort. Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness (CT) and white matter integrity) were analysed using linear mixed models in relation to anhedonia and PRS-anhedonia in 19,592 participants (9225 males; mean age = 62.6 years, SD = 7.44). We found that state anhedonia was significantly associated with reduced total grey matter volume (GMV); increased total white matter volume (WMV); smaller volumes in thalamus and nucleus accumbens; reduced CT within the paracentral cortex, the opercular part of inferior frontal gyrus, precentral cortex, insula and rostral anterior cingulate cortex; and poorer integrity of many white matter tracts. PRS-anhedonia was associated with reduced total GMV; increased total WMV; reduced white matter integrity; and reduced CT within the parahippocampal cortex, superior temporal gyrus and insula. Overall, both state anhedonia and PRS-anhedonia were associated with individual differences in multiple brain structures, including within reward-related circuits. These associations may represent vulnerability markers for psychopathology relevant to a range of psychiatric disorders.

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 Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joey Ward ◽  
Laura M. Lyall ◽  
Richard A. I. Bethlehem ◽  
Amy Ferguson ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Genetic Correlations ◽  
Grey Matter Volume ◽  
Obsessive Compulsive ◽  
Major Depressive ◽  
Compulsive Disorder ◽  
Matter Volume ◽  
Genome Wide

AbstractAnhedonia is a core symptom of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of state anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including orbito-frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of state anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this phenotype as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for state anhedonia influences brain structure, including in regions associated with reward and pleasure processing.

scholarly journals Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure

2019 ◽  
Author(s):  
Joey Ward ◽  
Laura M. Lyall ◽  
Richard A. I. Bethlehem ◽  
Amy Ferguson ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Genetic Correlations ◽  
Grey Matter Volume ◽  
Obsessive Compulsive ◽  
Major Depressive ◽  
Compulsive Disorder ◽  
Matter Volume ◽  
Genome Wide

AbstractAnhedonia is a core feature of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including nucleus accumbens, caudate and medial frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this trait as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for anhedonia influences brain structure, particularly in regions associated with reward and pleasure processing.

scholarly journals Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank imaging data

2016 ◽  
Author(s):  
Xueyi Shen ◽  
Lianne M. Reus ◽  
Simon R. Cox ◽  
Mark J. Adams ◽  
David C. Liewald ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
White Matter ◽  
Depressive Disorder ◽  
Grey Matter ◽  
White Matter Integrity ◽  
Grey Matter Volume ◽  
Uk Biobank ◽  
Imaging Data ◽  
Major Depressive ◽  
Matter Volume

AbstractPrevious reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n=1157) and white matter integrity (n=1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments. Whilst we found no significant differences in subcortical volumes, significant reductions were found in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) (β=-0.182, p=0.005). We also found reductions in FA in association/commissural fibres (β=-0.184, pcorrected=0.010) and thalamic radiations (β=-0.159, pcorrected=0.020). Tract-specific FA reductions were also found in the left superior longitudinal fasciculus (β=-0.194, pcorrected=0.025), superior thalamic radiation (β=-0.224, pcorrected=0.009) and forceps major (β=-0.193, pcorrected=0.025) in depression (all betas standardised). Our findings provide further evidence for disrupted white matter integrity in MDD.

scholarly journals Associations of cigarette smoking with gray and white matter in the UK Biobank

2019 ◽  
Author(s):  
Joshua Gray ◽  
Matthew Thompson ◽  
Chelsie Benca-Bachman ◽  
Max Michael Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Gray Matter ◽  
Brain Structure ◽  
Mean Diffusivity ◽  
Medial Lemniscus ◽  
Uk Biobank ◽  
Matter Volume ◽  
Increased Risk ◽  
The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

scholarly journals Genome-wide association studies of brain structure and function in the UK Biobank

2017 ◽  
Author(s):  
Lloyd T. Elliott ◽  
Kevin Sharp ◽  
Fidel Alfaro-Almagro ◽  
Sinan Shi ◽  
Karla Miller ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Brain Structure ◽  
Association Studies ◽  
Structure And Function ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
Brain Structure And Function ◽  
And Function

SummaryThe genetic basis of brain structure and function is largely unknown. We carried out genome-wide association studies of 3,144 distinct functional and structural brain imaging derived phenotypes in UK Biobank (discovery dataset 8,428 subjects). We show that many of these phenotypes are heritable. We identify 148 clusters of SNP-imaging associations with lead SNPs that replicate at p<0.05, when we would expect 21 to replicate by chance. Notable significant and interpretable associations include: iron transport and storage genes, related to changes in T2* in subcortical regions; extracellular matrix and the epidermal growth factor genes, associated with white matter micro-structure and lesion volume; genes regulating mid-line axon guidance development associated with pontine crossing tract organisation; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide new insight into the genetic architecture of the brain with relevance to complex neurological and psychiatric disorders, as well as brain development and aging. The full set of results is available on the interactive Oxford Brain Imaging Genetics (BIG) web browser.

scholarly journals Allostatic load as a predictor of grey matter volume and white matter integrity in old age: The Whitehall II MRI study

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Enikő Zsoldos ◽  
Nicola Filippini ◽  
Abda Mahmood ◽  
Clare E. Mackay ◽  
Archana Singh-Manoux ◽  
...  
Keyword(s):  
White Matter ◽  
Old Age ◽  
Allostatic Load ◽  
Grey Matter ◽  
White Matter Integrity ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Mri Study

scholarly journals Reproducible Risk Loci and Psychiatric Comorbidities in Anxiety: Results from ~200,000 Million Veteran Program Participants

2019 ◽  
Author(s):  
Daniel F. Levey ◽  
Joel Gelernter ◽  
Renato Polimanti ◽  
Hang Zhou ◽  
Zhongshan Cheng ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Psychiatric Disorders ◽  
Complex Traits ◽  
Association Studies ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Continuous Trait ◽  
Genome Wide ◽  
Program Sample

AbstractWe used GWAS in the Million Veteran Program sample (nearly 200,000 informative individuals) using a continuous trait for anxiety (GAD-2) to identify 5 genome-wide significant (GWS) signals for European Americans (EA) and 1 for African Americans. The strongest findings were on chromosome 3 (rs4603973, p=7.40×10−11) near the SATB1 locus, a global regulator of gene expression and on chromosome 6 (rs6557168, p=1.04×10−9) near ESR1 which encodes estrogen receptor α. A locus identified on chromosome 7 near MADIL1 (p=1.62×10−8) has been previously identified in GWAS of bipolar disorder and of schizophrenia and may represent a risk factor for psychiatric disorders broadly. SNP-based heritability was estimated to be ~6% for GAD-2. We also GWASed for self-reported anxiety disorder diagnoses (N=224,330) and identified two GWS loci, one (rs35546597, MAF=0.42, p=1.88×10−8) near the AURKB locus, and the other (rsl0534613, MAF=0.41, p=4.92×10−8) near the IQCHE and MADIL1 locus identified in the GAD-2 analysis. We demonstrate reproducibility by replicating our top findings in the summary statistics from the Anxiety NeuroGenetics Study (ANGST) and a UK Biobank neuroticism GWAS. We also replicated top findings from a large UK Biobank preprint, demonstrating stability of GWAS findings in complex traits once sufficient power is attained. Finally, we found evidence of significant genetic overlap between anxiety and major depression using polygenic risk scores, but also found that the main anxiety signals are independent of those for MDD. This work presents novel insights into the neurobiological risk underpinning anxiety and related psychiatric disorders.SignificanceAnxiety disorders are common and often disabling. They are also frequently co-morbid with other mental disorders such as major depressive disorder (MDD); these disorders may share commonalities in their underlying genetic architecture. Using one of the largest homogenously phenotyped cohorts available, the Million Veteran Program sample, we investigated common variants associated with anxiety in genome-wide association studies (GWASes), using survey results from the GAD-2 anxiety scale (as a continuous trait, n=199,611), and self-reported anxiety disorder diagnosis (as a binary trait, n=224,330). This largest GWAS to date for anxiety and related traits identified numerous novel significant associations, several of which are replicated in other datasets, and allows inference of underlying biology.

Associations of Diet Quality with Midlife Brain Volume: Findings from the UK Biobank Cohort Study

2021 ◽  
pp. 1-12
Author(s):  
Helen Macpherson ◽  
Sarah A. McNaughton ◽  
Karen E. Lamb ◽  
Catherine M. Milte
Keyword(s):  
Mediterranean Diet ◽  
Diet Quality ◽  
Brain Structure ◽  
Grey Matter ◽  
Brain Volume ◽  
Life Stage ◽  
Grey Matter Volume ◽  
Uk Biobank ◽  
Matter Volume ◽  
Diet Score

Background: Higher quality diets may be related to lower dementia rates. Midlife is emerging as a critical life stage for a number of dementia risk factors. Objective: This study examines whether diet quality is related to brain structure during midlife, and if this differs by sex. Methods: This study used data from 19184 UK Biobank participants aged 40–65 years. Diet quality was assessed using three dietary indices including the Mediterranean Diet Score (MDS), Healthy Diet Score (HDS), and Recommended Food Score (RFS). MRI brain measures included total, grey, white and hippocampal volume. Linear regression examined associations between diet quality and brain volume, controlling for potential confounders. Results: Better quality diet across all indices was significantly related to larger grey matter volume: MDS β= 429.7 (95%CI: 65.2, 794.2); HDS β= 700.1 (348.0, 1052.1); and RFS β= 317.1 (106.8, 527.3). Higher diet scores were associated with greater total volume: HDS β= 879.32 (286.13, 1472.50); RFS β= 563.37 (209.10, 917.65); and white matter volume: RFS β= 246.31 (20.56, 472.05), with the exception of Mediterranean diet adherence. Healthy eating guidelines and dietary variety associations with total and grey matter volume were more prominent in men. Conclusion: Findings suggest that diet quality is associated with brain structure during midlife, potentially decades prior to the onset of dementia.

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