scholarly journals Cortical and Subcortical Brain Volumes Partially Mediate the Association between Dietary Composition and Behavioral Disinhibition: A UK Biobank Study

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3542
Author(s):  
Daan van Rooij ◽  
Lizanne Schweren ◽  
Huiqing Shi ◽  
Catharina A Hartman ◽  
Jan K Buitelaar
Keyword(s):  
Brain Volume ◽  
Adult Population ◽  
Dietary Quality ◽  
Outcome Variable ◽  
Behavioral Disinhibition ◽  
Dietary Composition ◽  
Uk Biobank ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Dietary Components

Behavioral disinhibition is observed to be an important characteristic of many neurodevelopmental and psychiatric disorders. Recent studies have linked dietary quality to levels of behavioral inhibition. However, it is currently unclear whether brain factors might mediate this. The current study investigates whether cortical and subcortical brain volumes mediate part of the association between dietary composition and behavioral disinhibition. A total of 15,258 subjects from the UK Biobank project were included in the current study. Dietary composition and behavioral disinhibition were based on Principle Component Analyses of self-reported dietary composition). As a further data reduction step, cortical and subcortical volume segmentations were input into an Independent Component Analysis. The resulting four components were used as mediator variables in the main mediation analyses, where behavioral disinhibition served as the outcome variable and dietary components as predictors. Our results show: (1) significant associations between all dietary components and brain volume components; (2) brain volumes are associated with behavioral disinhibition; (3) the mediation models show that part of the variance in behavioral disinhibition explained by dietary components (for healthy diet, restricted diet, and high-fat dairy diet) is mediated through the frontal-temporal/parietal brain volume component. These results are in part confirming our hypotheses and offer a first insight into the underlying mechanisms linking dietary composition, frontal-parietal brain volume, and behavioral disinhibition in the general adult population.

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.

scholarly journals Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank

2019 ◽  
Vol 25 (4) ◽  
pp. 854-862 ◽  
Author(s):  
Anthony Warland ◽  
Kimberley M. Kendall ◽  
Elliott Rees ◽  
George Kirov ◽  
Xavier Caseras
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Uk Biobank ◽  
Brain Volumes ◽  
Genomic Copy Number ◽  
Subcortical Brain ◽  
Genomic Copy ◽  
The Uk

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 Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank

2018 ◽  
Author(s):  
Anthony Warland ◽  
Kimberley M Kendall ◽  
Elliott Rees ◽  
George Kirov ◽  
Xavier Caseras
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Risk Groups ◽  
Clinical Samples ◽  
Uk Biobank ◽  
Subcortical Structures ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Heritable Disorder ◽  
The Uk

AbstractSchizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations have been observed between neuroanatomical phenotypes and known genetic risk factors for schizophrenia. We tested subcortical brain volume differences between 49 unaffected participants carrying at least one of the 12 copy number variants associated with schizophrenia in UK Biobank and 9,063 individuals who did not carry any of the 93 copy number variants reported to be pathogenic. Our results show that CNV carriers have reduced volume in some of the subcortical structures previously shown to be reduced in schizophrenia. Moreover, these associations were partially accounted for by the association between pathogenic copy number variants and cognitive impairment, which is one of the features of schizophrenia.

scholarly journals Evaluating the effect of birth weight on brain volumes and depression: An observational and genetic study using UK Biobank cohort

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Jing Ye ◽  
Cuiyan Wu ◽  
Xiaomeng Chu ◽  
Yan Wen ◽  
Ping Li ◽  
...  
Keyword(s):  
Birth Weight ◽  
Gray Matter ◽  
Mediation Analysis ◽  
Brain Volume ◽  
Mediation Effect ◽  
Risk Scores ◽  
Uk Biobank ◽  
Phenotypic Data ◽  
Brain Volumes ◽  
Mediation Effects

Abstract Background. Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear. Methods. The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations. Result. We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014). Conclusions. Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.

scholarly journals Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use

2021 ◽  
pp. 1-9
Author(s):  
Emma Logtenberg ◽  
Martin F. Overbeek ◽  
Joëlle A. Pasman ◽  
Abdel Abdellaoui ◽  
Maartje Luijten ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Genetic Variants ◽  
Brain Volume ◽  
Hippocampal Volume ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Causal Nature ◽  
Relationship Of

Background Structural variation in subcortical brain regions has been linked to substance use, including the most commonly used substances nicotine and alcohol. Pre-existing differences in subcortical brain volume may affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. Aims We assess the causal nature of the complex relationship of subcortical brain volume with smoking and alcohol use, using bi-directional Mendelian randomisation. Method Mendelian randomisation uses genetic variants predictive of a certain ‘exposure’ as instrumental variables to test causal effects on an ‘outcome’. Because of random assortment at meiosis, genetic variants should not be associated with confounders, allowing less biased causal inference. We used summary-level data of genome-wide association studies of subcortical brain volumes (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus; n = 50 290) and smoking and alcohol use (smoking initiation, n = 848 460; cigarettes per day, n = 216 590; smoking cessation, n = 378 249; alcoholic drinks per week, n = 630 154; alcohol dependence, n = 46 568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results There was strong evidence that liability to alcohol dependence decreased amygdala and hippocampal volume, and smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and likely mental health, warranting more recognition in public health efforts.

scholarly journals Stereological Investigation of Regional Brain Volumes after Acute and Chronic Cuprizone-Induced Demyelination

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1024 ◽  
Author(s):  
Tanja Hochstrasser ◽  
Sebastian Rühling ◽  
Kerstin Hecher ◽  
Kai H. Fabisch ◽  
Uta Chrzanowski ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Brain Volume ◽  
Internal Capsule ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Male Mice ◽  
Neuroprotective Effects ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Underlying Mechanisms

Brain volume measurement is one of the most frequently used biomarkers to establish neuroprotective effects during pre-clinical multiple sclerosis (MS) studies. Furthermore, whole-brain atrophy estimates in MS correlate more robustly with clinical disability than traditional, lesion-based metrics. However, the underlying mechanisms leading to brain atrophy are poorly understood, partly due to the lack of appropriate animal models to study this aspect of the disease. The purpose of this study was to assess brain volumes and neuro-axonal degeneration after acute and chronic cuprizone-induced demyelination. C57BL/6 male mice were intoxicated with cuprizone for up to 12 weeks. Brain volume, as well as total numbers and densities of neurons, were determined using design-based stereology. After five weeks of cuprizone intoxication, despite severe demyelination, brain volumes were not altered at this time point. After 12 weeks of cuprizone intoxication, a significant volume reduction was found in the corpus callosum and diverse subcortical areas, particularly the internal capsule and the thalamus. Thalamic volume loss was accompanied by glucose hypermetabolism, analyzed by [18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography. This study demonstrates region-specific brain atrophy of different subcortical brain regions after chronic cuprizone-induced demyelination. The chronic cuprizone demyelination model in male mice is, thus, a useful tool to study the underlying mechanisms of subcortical brain atrophy and to investigate the effectiveness of therapeutic interventions.

scholarly journals The Association of Age at Diagnosis of Hypertension With Brain Structure and Incident Dementia in the UK Biobank

Hypertension ◽  
2021 ◽  
Author(s):  
Xianwen Shang ◽  
Edward Hill ◽  
Zhuoting Zhu ◽  
Jiahao Liu ◽  
B. Zongyuan Ge ◽  
...  
Keyword(s):  
Gray Matter ◽  
Brain Volume ◽  
Multivariable Analysis ◽  
Brain Magnetic Resonance Imaging ◽  
Hospital Inpatient ◽  
Uk Biobank ◽  
Brain Volumes ◽  
Increased Risk ◽  
The Uk ◽  
Diagnosis Of Hypertension

Little is known about whether the association of hypertension with brain volume and dementia is modified by an individual’s age at their diagnosis of hypertension. Our analysis was based on the UK Biobank with baseline data collected between 2006 and 2010. Brain magnetic resonance imaging was used to measure brain volumes between 2014 and 2019. Dementia was ascertained using hospital inpatient, mortality, and self-reported data until 2021. We randomly selected a control participant for each hypertensive participant stratified by hypertension diagnosis age using propensity score. The cohort comprised 11 399 individuals with hypertension and 11 399 controls for the brain volume analysis and 124 053 individuals with hypertension and 124 053 controls for the dementia analysis. Individuals with hypertension diagnosed at ages <35 (β (95% CI, −10.83 [−19.27 to −2.39] mL), 35 to 44 (−6.82 [−12.18 to −1.46] mL), and 45 to 54 years (−3.77 [−6.91 to −0.64] mL) had smaller total brain volume compared with the corresponding controls in the multivariable analysis. Similarly, hypertension diagnosed in early- and mid-life was independently associated with smaller volumes of gray matter, peripheral cortical gray matter, and white matter. Over a median follow-up of 11.9 years, 4626 cases of incident all-cause dementia were documented. Individuals with hypertension diagnosed at 35 to 44 years of age only (hazard ratio [95% CI]: 1.61 [1.31–1.99]) had a higher risk of all-cause dementia compared with the corresponding controls after adjustment for covariates. Hypertension diagnosed in young adulthood or mid-life, but not late life is associated with smaller brain volumes and an increased risk of dementia.

scholarly journals Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1790
Author(s):  
Samuel Berkins ◽  
Helgi Birgir Schiöth ◽  
Gull Rukh
Keyword(s):  
Vitamin B12 ◽  
Brain Structure ◽  
Vitamin B6 ◽  
Significant Interaction ◽  
Longitudinal Design ◽  
Folate Intake ◽  
Dietary Vitamin ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Depression Status

Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.

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