scholarly journals Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior

2021 ◽  
Author(s):  
Ronald de Vlaming ◽  
Eric A.W. Slob ◽  
Philip R Jansen ◽  
Alain Dagher ◽  
Philipp D. Koellinger ◽  
...  
Keyword(s):  
Grey Matter ◽  
Behavioral Outcomes ◽  
Genetic Correlations ◽  
Brain Morphology ◽  
Grey Matter Volume ◽  
Behavioral Traits ◽  
And Behavior ◽  
The Brain ◽  
Genomic Relatedness ◽  
Shared Genetic

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce multivariate genomic-relatedness restricted maximum likelihood (MGREML) and provide estimates of the heritability of grey-matter volume in 74 regions of interest (ROIs) in the brain. We map genetic correlations between these ROIs and health-relevant behavioral outcomes including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs.

scholarly journals Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ronald de Vlaming ◽  
Eric A. W. Slob ◽  
Philip R. Jansen ◽  
Alain Dagher ◽  
Philipp D. Koellinger ◽  
...  
Keyword(s):  
Genetic Correlation ◽  
Gray Matter Volume ◽  
Genetic Correlations ◽  
Brain Morphology ◽  
Computationally Efficient ◽  
Individual Level ◽  
Level Data ◽  
The Uk ◽  
And Behavior ◽  
The Brain

AbstractHuman variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets.

scholarly journals Sex differences in neural correlates of common psychopathological symptoms in early adolescence

2021 ◽  
pp. 1-11
Author(s):  
Francesca Biondo ◽  
Charlotte Nymberg Thunell ◽  
Bing Xu ◽  
Congying Chu ◽  
Tianye Jia ◽  
...  
Keyword(s):  
Internalizing Symptoms ◽  
Grey Matter ◽  
Neural Correlates ◽  
Brain Regions ◽  
Female Adolescents ◽  
Grey Matter Volume ◽  
Community Based ◽  
Psychopathological Symptom ◽  
Strengths And Difficulties ◽  
The Brain

Abstract Background Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence. Methods Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ). Results We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls. Conclusions Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.

scholarly journals Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior

2009 ◽  
Vol 106 (17) ◽  
pp. 7203-7208 ◽  
Author(s):  
Pei-Yu Wang ◽  
Anna Protheroe ◽  
Andrew N. Clarkson ◽  
Floriane Imhoff ◽  
Kyoko Koishi ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Reproductive Tract ◽  
Behavioral Traits ◽  
Spinal Motor Neurons ◽  
Müllerian Inhibiting Substance ◽  
Males And Females ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain ◽  
Mullerian Inhibiting Substance

Many behavioral traits and most brain disorders are common to males and females but are more evident in one sex than the other. The control of these subtle sex-linked biases is largely unstudied and has been presumed to mirror that of the highly dimorphic reproductive nuclei. Sexual dimorphism in the reproductive tract is a product of Müllerian inhibiting substance (MIS), as well as the sex steroids. Males with a genetic deficiency in MIS signaling are sexually males, leading to the presumption that MIS is not a neural regulator. We challenge this presumption by reporting that most immature neurons in mice express the MIS-specific receptor (MISRII) and that male Mis−/− and Misrii−/− mice exhibit subtle feminization of their spinal motor neurons and of their exploratory behavior. Consequently, MIS may be a broad regulator of the subtle sex-linked biases in the nervous system.

scholarly journals Shared genetic etiology between cortical brain morphology and tobacco, alcohol, and cannabis use

2021 ◽  
Author(s):  
Jill A. Rabinowitz ◽  
Adrian I. Campos ◽  
Jue-Sheng Ong ◽  
Luis M. García-Marín ◽  
Sarael Alcauter ◽  
...  
Keyword(s):  
Substance Use ◽  
Surface Area ◽  
Brain Structure ◽  
Genetic Correlations ◽  
Cannabis Use ◽  
Brain Morphology ◽  
Equation Modeling ◽  
Genetic Etiology ◽  
Genetic Overlap ◽  
Shared Genetic

ABSTRACTGenome-wide association studies (GWAS) have independently identified hundreds of genomic regions associated with brain morphology and substance use. However, the genetic overlap between brain structure and substance use has not been characterized. Here we leverage GWAS summary data of 71 brain imaging measures and alcohol, tobacco, and cannabis use to investigate their genetic overlap using LD score regression. We also used genomic structural equation modeling to model a ‘substance use common genetic factor’ and examined its genetic overlap with brain structure. After accounting for multiple testing, we identified eight significant negative genetic correlations, including between alcoholic drinks per week and average cortical thickness and intracranial volume with the age of smoking initiation; and five positive genetic correlations, including between insula surface area and lifetime cannabis use, and between the common factor with pericalcarine surface area. Our findings highlight a shared genetic etiology between variation in cortical brain morphology and substance use.

scholarly journals INFLUENCE OF PSYCHOTIC EPISODES ON GREY MATTER VOLUME CHANGES IN PATIENTS WITH SCHIZOPHRENIA

2020 ◽  
Author(s):  
Antonija Ružić Baršić ◽  
Gordana Rubeša ◽  
Diana Mance ◽  
Damir Miletić ◽  
Lea Gudelj ◽  
...  
Keyword(s):  
Grey Matter ◽  
Disease Duration ◽  
Severe Illness ◽  
Grey Matter Volume ◽  
Healthy Controls ◽  
Voxel Based Morphometry ◽  
Matter Volume ◽  
Multiple Regions ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Background: Schizophrenia is a severe illness whose clinical course is characterized by various numbers of psychotic episodes (PE). The neurotoxic hypothesis (NH) of schizophrenia assumes that psychosis is biologically toxic. The aim of the study was to investigate whether schizophrenia patients (SP) with multiple PE have greater grey matter volume (GMV) reduction compared to SP with fewer PE.Subjects and methods: We enrolled 106 adult SP and 63 healthy controls. Demographic and clinical data were collected and statistically analysed for all included subjects. Magnetic resonance imaging (MRI) of the brain was acquired on a 1.5 T scanner. SP were grouped according to the number of PE into a group with up to 3 PE (SCHG-1) and with 4 or more PE (SCHG-2). SCHG-1 was further subdivided into two groups regarding to disease duration (DD). Voxel based morphometry (VBM) analyses were performed between SP groups as well as between SP groups and the healthy controls group (HCG).Results: No relevant GMV differences were detected between SP groups. Comparison between HCG and SCHG-1 showed only 3 regions with reduced GMV, while multiple regions with reduced GMV were detected when comparing HCG and SCHG-2. Conclusions: GMV reduction in schizophrenia varies depending on the number of PE when compared to HCG, regardless of disease duration (DD), but PE is not the only contributing factor that leads to neurotoxicity.

scholarly journals Human brain anatomy reflects separable genetic and environmental components of socioeconomic status

2021 ◽  
Author(s):  
Hyeokmoon Kweon ◽  
Gokhan Aydogan ◽  
Alain Dagher ◽  
Danilo Bzdok ◽  
Christian C Ruff ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Grey Matter ◽  
Brain Regions ◽  
Grey Matter Volume ◽  
Brain Anatomy ◽  
Additive Effects ◽  
Common Genetic Variation ◽  
Matter Volume ◽  
Underlying Causes ◽  
The Brain

Recent studies report that socioeconomic status (SES) correlates with brain structure. Yet, such findings are variable and little is known about underlying causes. We present a well-powered voxel-based analysis of grey matter volume (GMV) across levels of SES, finding many small SES effects widely distributed across the brain, including cortical, subcortical and cerebellar regions. We also construct a polygenic index of SES to control for the additive effects of common genetic variation related to SES, which attenuates observed SES-GMV relations, to different degrees in different areas. Remaining variance, which may be attributable to environmental factors, is substantially accounted for by body mass index, a marker for lifestyle related to SES. In sum, SES affects multiple brain regions through measurable genetic and environmental effects.

scholarly journals Insight from animal models of environmentally driven epigenetic changes in the developing and adult brain

2016 ◽  
Vol 28 (4pt2) ◽  
pp. 1229-1243 ◽  
Author(s):  
Tiffany S. Doherty ◽  
Tania L. Roth
Keyword(s):  
Central Nervous System ◽  
Animal Models ◽  
Behavioral Outcomes ◽  
Adult Brain ◽  
Epigenetic Changes ◽  
Behavioral Deficits ◽  
The Central Nervous System ◽  
Brain And Behavior ◽  
And Behavior ◽  
The Brain

AbstractThe efforts of many neuroscientists are directed toward understanding the appreciable plasticity of the brain and behavior. In recent years, epigenetics has become a core of this focus as a prime mechanistic candidate for behavioral modifications. Animal models have been instrumental in advancing our understanding of environmentally driven changes to the epigenome in the developing and adult brain. This review focuses mainly on such discoveries driven by adverse environments along with their associated behavioral outcomes. While much of the evidence discussed focuses on epigenetics within the central nervous system, several peripheral studies in humans who have experienced significant adversity are also highlighted. As we continue to unravel the link between epigenetics and phenotype, discerning the complexity and specificity of epigenetic changes induced by environments is an important step toward understanding optimal development and how to prevent or ameliorate behavioral deficits bred by disruptive environments.

scholarly journals Shared Genetic Etiology between Cortical Brain Morphology and Tobacco, Alcohol, and Cannabis Use

2021 ◽  
Author(s):  
Jill A Rabinowitz ◽  
Adrian I Campos ◽  
Jue-Sheng Ong ◽  
Luis M García-Marín ◽  
Sarael Alcauter ◽  
...  
Keyword(s):  
Surface Area ◽  
Brain Structure ◽  
Genetic Variants ◽  
Genetic Factor ◽  
Genetic Correlations ◽  
Cannabis Use ◽  
Brain Morphology ◽  
Genetic Etiology ◽  
Genetic Overlap ◽  
Shared Genetic

Abstract Genome-wide association studies (GWAS) have identified genetic variants associated with brain morphology and substance use behaviors (SUB). However, the genetic overlap between brain structure and SUB has not been well characterized. We leveraged GWAS summary data of 71 brain imaging measures and alcohol, tobacco, and cannabis use to investigate their genetic overlap using linkage disequilibrium score regression. We used genomic structural equation modeling to model a “common SUB genetic factor” and investigated its genetic overlap with brain structure. Furthermore, we estimated SUB polygenic risk scores (PRS) and examined whether they predicted brain imaging traits using the Adolescent Behavior and Cognitive Development (ABCD) study. We identified 8 significant negative genetic correlations, including between (1) alcoholic drinks per week and average cortical thickness, and (2) intracranial volume with age of smoking initiation. We observed 5 positive genetic correlations, including those between (1) insula surface area and lifetime cannabis use, and (2) the common SUB genetic factor and pericalcarine surface area. SUB PRS were associated with brain structure variation in ABCD. Our findings highlight a shared genetic etiology between cortical brain morphology and SUB and suggest that genetic variants associated with SUB may be causally related to brain structure differences.

scholarly journals Functional and structural magnetic resonance imaging correlates of fatigue in patients with rheumatoid arthritis

Rheumatology ◽  
2019 ◽  
Vol 58 (10) ◽  
pp. 1822-1830 ◽  
Author(s):  
Neil Basu ◽  
Chelsea M Kaplan ◽  
Eric Ichesco ◽  
Tony Larkin ◽  
Andrew Schrepf ◽  
...  
Keyword(s):  
Grey Matter ◽  
Imaging Study ◽  
Structural Mri ◽  
Grey Matter Volume ◽  
Voxel Based Morphometry ◽  
Neural Imaging ◽  
Dorsal Attention Network ◽  
Mri Changes ◽  
Structural Mode ◽  
The Brain

Abstract Objectives Fatigue is a major burden among patients with RA, yet is poorly understood. We sought to conduct the first imaging study to investigate the neurobiological correlates of fatigue in RA and to improve upon the methodological limitations of previous neuroimaging studies that have investigated this symptom in other populations. Methods Chronically fatigued RA patients were clinically characterized before undertaking a combined functional and structural mode MRI brain scan. The functional sequences were acquired during a fatigue-evoking task, then network-to-whole-brain analyses were undertaken. The structural analyses employed voxel-based morphometry in order to quantify regional grey matter volume. The scan was repeated 6 months later to test reproducibility. Results Fifty-four participants attended both scans [n = 41 female; baseline mean (s.d.) age 54.94 (11.41) years]. A number of significant functional and structural neural imaging correlates of fatigue were identified. Notably, patients who reported higher levels of fatigue demonstrated higher levels of functional connectivity between the Dorsal Attention Network and medial prefrontal gyri, a finding that was reproduced in the repeat scans. Structurally, greater putamen grey matter volumes significantly correlated with greater levels of fatigue. Conclusion Fatigue in RA is associated with functional and structural MRI changes in the brain. The newly identified and reproduced neural imaging correlates provide a basis for future targeting and stratification of this key patient priority.

scholarly journals The Plastic Adaptation to Pathology in Psychiatry. Are Patients with Psychiatric Disorders Pathological Experts?

2018 ◽  
Author(s):  
Ali Amad ◽  
Paul Expert ◽  
Louis-David Lord ◽  
Thomas Fovet ◽  
Pierre A. Geoffroy
Keyword(s):  
Psychiatric Disorders ◽  
Chronic Inflammation ◽  
Grey Matter ◽  
Psychiatric Symptoms ◽  
Brain Connectivity ◽  
Diagnosis And Treatment ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
The Brain ◽  
New Framework

Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.

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