The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single nucleotide polymorphisms-based analyses of 38127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

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Mid-sagittal anatomy in late-onset schizophrenia

Psychological Medicine ◽

10.1017/s0033291799008685 ◽

1999 ◽

Vol 29 (4) ◽

pp. 963-970 ◽

Cited By ~ 15

Author(s):

PERMINDER S. SACHDEV ◽

HENRY BRODATY

Keyword(s):

Corpus Callosum ◽

Late Onset ◽

Brain Structures ◽

Brain Regions ◽

Cross Sectional ◽

Significant Difference ◽

Comparison Groups ◽

Schizophrenic Patients ◽

Independent Replication ◽

And Gender

Background. Of the midline brain structures, abnormalities have been demonstrated in the corpus callosum and cerebellum in young schizophrenic patients. Whether similar abnormalities are also present in late-onset schizophrenia (LOS) is not known.Methods. The mid-sagittal cross-sectional areas of brain regions, in particular the corpus callosum and cerebellum, on magnetic resonance imaging were examined in a group of patients with late-onset schizophrenia (N=25) and contrasted with two comparison groups – early-onset schizophrenia (EOS) (N=2524) and healthy volunteers (NC) (N=2530) matched for age and gender.Results. While the mean corpus callosum area in the LOS group was smaller than in the EOS (by 10·2%) and NC (by 6·2%) groups, the three groups did not differ statistically in the corpus callosum area or the corpus callosum to cerebrum ratios. The cross-sectional cerebellar areas or the cerebellum: cerebrum ratios also did not differ across the groups. The brainstem was smaller in the schizophrenic groups because of smaller cross-sectional areas of the pons, a statistically significant difference which could not be accounted for by any gross lesions on visual inspection.Conclusion. We found no abnormality in the mid-sagittal area of the corpus callosum and cerebellum in our early- or late-onset schizophrenia subjects. The significance of the finding of a smaller pontine cross-sectional area is unclear and speculation on it awaits independent replication using a volumetric measure.

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Brain α-tocopherol concentration is inversely associated with neurofibrillary tangle counts in brain regions affected in earlier Braak stages: A cross-sectional finding in the oldest old

Journal of Aging Research and Lifestyle ◽

10.14283/jarlife.2021.2 ◽

2021 ◽

pp. 1-9

Author(s):

J. Tanprasertsuk ◽

T.M. Scott ◽

M.A. Johnson ◽

L.W. Poon ◽

P.T. Nelson ◽

...

Keyword(s):

Vitamin E ◽

Oldest Old ◽

Neurofibrillary Tangle ◽

Brain Structures ◽

Brain Regions ◽

Phase Iii ◽

Neuritic Plaque ◽

Tocopherol Concentration ◽

Cross Sectional ◽

Braak Staging

Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer’s disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of α- and γ-tocopherol and the severity of AD pathologies – neurofibrillary tangle (NFT) and neuritic plaque (NP) – was investigated. Setting & Participants: Brains from 43 centenarians (≥ 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain α- and γ-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (β = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (β = -2.01, 95% CI [-3.72, -0.30]), hippocampus (β = -2.23, 95% CI [-3.82, -0.64]), and subiculum (β = -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower α-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.

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Large-scale exploration of whole-brain structural connectivity in anorexia nervosa: alterations in the connectivity of frontal and subcortical networks

10.1101/2021.10.05.463197 ◽

2021 ◽

Author(s):

E. Caitlin Lloyd ◽

Karin E. Foerde ◽

Alexandra F. Muratore ◽

Natalie Aw ◽

David Semanek ◽

...

Keyword(s):

Anorexia Nervosa ◽

Graph Theory ◽

Linear Regression ◽

Multiple Linear Regression ◽

Large Scale ◽

Structural Connectivity ◽

Brain Regions ◽

Cross Sectional ◽

Whole Brain ◽

Subcortical Regions

AbstractBackgroundAnorexia nervosa (AN) is characterised by disturbances in cognition and behaviour surrounding eating and weight, which may relate to the structural connectivity of the brain that supports effective information processing and transfer.MethodsDiffusion-weighted MRI data acquired from female patients with AN (n = 148) and female healthy controls (HC; n = 119), aged 12-40 years, were combined across five cross-sectional studies. Probabilistic tractography was completed, and full cortex connectomes describing streamline counts between 84 brain regions generated and harmonised. The network-based statistic tested between-group differences in connectivity strength of brain subnetworks. Whole-brain connectivity of brain regions was indexed using graph theory tools, and compared between groups using multiple linear regression. Associations between structural connectivity variables that differed between groups, and illness severity markers, were explored amongst AN patients using multiple linear regression. Statistical models included age, motion, and study as covariates.OutcomesThe network-based statistic indicated AN patients, relative to HC, had reduced connectivity in a network comprising subcortical regions and greater connectivity between frontal cortical regions (p < 0.05, FWE corrected). Graph theory analyses supported reduced connectivity of subcortical regions, and greater connectivity of left occipital cortex, in patients relative to HC (p < 0.05, permutation corrected). Reduced subcortical network connectivity was associated with lower BMI among the AN group.InterpretationStructural differences in subcortical and cortical networks are present in AN, and may reflect illness mechanisms.FundingGlobal Foundation for Eating Disorders; Klarman Family Foundation; Translating Duke Health Initiative; NIMH (MH099388, MH076195, MH110445, MH105452, MH079397, MH113737).

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The genetic organization of subcortical volumetric change is stable throughout the lifespan

10.1101/2020.06.12.143834 ◽

2020 ◽

Author(s):

Anders M Fjell ◽

Håkon Grydeland ◽

Yunpeng Wang ◽

Inge Amlien ◽

David Bartrés-Faz ◽

...

Keyword(s):

Cerebral Cortex ◽

Cognitive Function ◽

Brain Development ◽

Embryonic Brain ◽

Subcortical Structures ◽

Single Nucleotide ◽

Genetic Organization ◽

Development And Aging ◽

Subcortical Regions ◽

Embryonic Brain Development

AbstractWhile development and aging of the cerebral cortex show a similar topographic organization and are mainly governed by the same genes, it is unclear whether the same is true for subcortical structures, which follow fundamentally different ontogenetic and phylogenetic principles than the cerebral cortex. To test the hypothesis that genetically governed neurodevelopmental processes can be traced in subcortical structures throughout life, we analyzed a longitudinal magnetic resonance imaging dataset (n = 974, age 4-89 years), identifying five clusters of longitudinal change in development. With some exceptions, these clusters followed placement along the cranial axis in embryonic brain development, suggesting continuity in the pattern of change from prenatal stages. Developmental change patterns were conserved through the lifespan and predicted general cognitive function in an age-invariant manner. The results were replicated in longitudinal data from the Lifebrain consortium (n = 756, age 19-83 years). Genetic contributions to longitudinal brain changes were calculated from the Vietnam Era Twin Study of Aging (n = 331 male twins, age 51-60 years), revealing that distinct sets of genes tended to govern change for each developmental cluster. This finding was confirmed with single nucleotide polymorphisms and cross-sectional MRI data from the UK Biobank (n = 20,588, age 40-69), demonstrating significantly higher co-heritability among structures belonging to the same developmental clusters. Together, these results suggest that coordination of subcortical change adheres to fundamental principles of lifespan continuity, genetic organization and age-invariant relationships to cognitive function.Significance statementHere we show that subcortical change during childhood development is organized in clusters. These clusters tend to follow the main gradient of embryonic brain development, and are stable across life. This means that subcortical regions changing together in childhood also change together throughout the rest of life, in accordance with a lifespan perspective on brain development and aging. Twin and single nucleotide polymorphism-based heritability analyses in middle-aged and older adults showed that volume and volume change of regions within each developmental cluster tended to be governed by the same sets of genes. Thus, volumetric changes across subcortical regions are tightly organized, and the coordinated change can be described in a lifespan perspective according to ontogenetic and genetic influences.

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Volumetric MRI analysis of brain structures in patients with history of first and repeated suicide attempts: a cross sectional study

10.21203/rs.3.rs-36981/v2 ◽

2020 ◽

Author(s):

Milda Sarkinaite ◽

Rymante Gleizniene ◽

Virginija Adomaitiene ◽

Kristina Dambrauskiene ◽

Nijole Raskauskiene ◽

...

Keyword(s):

Suicide Attempt ◽

Left Hemisphere ◽

Cortical Thickness ◽

Suicide Attempts ◽

Right Hemisphere ◽

Brain Structures ◽

Brain Regions ◽

Cross Sectional ◽

Suicide Attempters ◽

History Of

Abstract Background Structural brain changes are found in suicide attempters, as well as in patients with mental disorders. It remains unclear whether the suicidal behavior is related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. This cross-sectional study examined volumetric differences in brain regions among patients with history of first and repeated suicide attempts in comparison to healthy controls (HC). Methods The sample consisted of 56 adults, non-psychotic patients without cognitive impairment and any organic brain disorders hospitalized after first suicide attempt (first SA) (n=29) and more than one suicide attempt (SA>1) during the lifetime (n=27); and 54 adult volunteers without history of mental disorder and suicide attempts, designated as HC. The MRI data were collected using 1.5 T Siemens Avanto scanner. Brain cortical thickness, grey and white matter volumes were measured using FreeSurfer 6.0 automatic segmentation technique. Results In comparison to HC, patients with first SA had 3.5, 3.58 and 4.19% significantly lower mean cortical thickness of the superior and rostral middle frontal areas of the left hemisphere and superior frontal area of the right hemisphere, respectively; 4.09, 4.02 and 4.49% lower mean cortical thickness of the inferior, middle and superior temporal areas of the left hemisphere, respectively. In comparison to HC, patients after SA>1 had a significantly lower mean cortical thickness (from 4.02 to 8.33%) in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere; from 3.90 to 6.04% difference in six areas of temporal cortex in both hemispheres. The comparison of hippocampus volume showed a significantly lower mean volume (7.86 to 9.89%) of left and right parts in patients with SA>1, but not in patients with first SA. Conclusions Hospitalized suicide attempters had lower frontal and temporal cortical thickness and smaller parts of hippocampus than HC; these differences were significantly higher in repeated suicide attempters than in patients with first SA. Our findings suggest that repeated suicidal behavior is associated with intensifying atrophy of specific brain structures, independently of diagnosis of depressive disorders.

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Volumetric MRI Analysis of Brain Structures in Patients With History of First and Repeated Suicide Attempts: A Cross Sectional Study

10.21203/rs.3.rs-36981/v1 ◽

2020 ◽

Author(s):

Milda Sarkinaite ◽

Rymante Gleizniene ◽

Virginija Adomaitiene ◽

Kristina Dambrauskiene ◽

Nijole Raskauskiene ◽

...

Keyword(s):

Suicide Attempt ◽

Left Hemisphere ◽

Cortical Thickness ◽

Suicide Attempts ◽

Right Hemisphere ◽

Brain Structures ◽

Brain Regions ◽

Cross Sectional ◽

Suicide Attempters ◽

History Of

Abstract Background: Structural brain changes are found in suicide attempters, as well as in patients with mental disorders. It remains unclear whether the suicidal behavior is related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. This cross-sectional study examined volumetric differences in brain regions among patients with history of first and repeated suicide attempts in comparison to healthy controls (HC).Methods: The sample consisted of 56 adults, non-psychotic patients without cognitive impairment and any organic brain disorders hospitalized after first suicide attempt (first SA) (n=29) and more than one suicide attempt (SA>1) during the lifetime (n=27); and 54 adult volunteers without history of mental disorder and suicide attempts, designated as HC. The MRI data were collected using 1.5 T Siemens Avanto scanner. Brain cortical thickness, grey and white matter volumes were measured using FreeSurfer 6.0 automatic segmentation technique.Results: In comparison to HC, patients with first SA had 3.5, 3.58 and 4.19% significantly lower mean cortical thickness of the superior and rostral middle frontal areas of the left hemisphere and superior frontal area of the right hemisphere, respectively; 4.09, 4.02 and 4.49 % lower mean cortical thickness of the inferior, middle and superior temporal areas of the left hemisphere, respectively. In comparison to HC, patients after SA>1 had a significantly lower mean cortical thickness (from 4.02 to 8.33%) in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere; from 3.90 to 6.04% difference in six areas of temporal cortex in both hemispheres. The comparison of hippocampus volume showed a significantly lower mean volume (7.86 to 9.89%) of left and right parts in patients with SA>1, but not in patients with first SA. Conclusions: Hospitalized suicide attempters had lower frontal and temporal cortical thickness and smaller parts of hippocampus than HC; these differences were significantly higher in repeated suicide attempters than in patients with first SA. Our findings suggest that repeated suicidal behavior is associated with intensifying atrophy of specific brain structures, independently of diagnosis of depressive disorders.

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Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium

10.1101/409649 ◽

2018 ◽

Cited By ~ 4

Author(s):

Edith Hofer ◽

Gennady V. Roshchupkin ◽

Hieab H. H. Adams ◽

Maria J. Knol ◽

Honghuang Lin ◽

...

Keyword(s):

Surface Area ◽

Meta Analysis ◽

Genetic Correlations ◽

Brain Regions ◽

Aging Research ◽

Genomic Epidemiology ◽

Discovery Sample ◽

Genome Wide ◽

Development And Aging ◽

Pathway Analyses

AbstractCortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

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Altered cortico-subcortical network after adolescent alcohol exposure mediates behavioral deficits in flexible decision-making

10.1101/2021.03.12.435040 ◽

2021 ◽

Author(s):

Alexander Gómez-A ◽

Carol A. Dannenhoffer ◽

Amanda Elton ◽

SungHo Lee ◽

Woomi Ban ◽

...

Keyword(s):

Decision Making ◽

Functional Connectivity ◽

Behavioral Flexibility ◽

Alcohol Exposure ◽

Brain Structures ◽

Brain Regions ◽

Resting State Functional Connectivity ◽

Mediation Analyses ◽

Adolescent Alcohol ◽

Subcortical Regions

AbstractBehavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and functional connectivity in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.

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Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Nature Communications ◽

10.1038/s41467-020-18367-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Edith Hofer ◽

◽

Gennady V. Roshchupkin ◽

Hieab H. H. Adams ◽

Maria J. Knol ◽

...

Keyword(s):

Sonic Hedgehog ◽

Genetic Correlations ◽

Brain Regions ◽

Aging Research ◽

Genomic Epidemiology ◽

Discovery Sample ◽

Genome Wide ◽

Psychiatric Conditions ◽

Development And Aging ◽

The Uk

Abstract Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

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Personality's Correlates of Adult Development and Aging

European Psychologist ◽

10.1027//1016-9040.8.3.131 ◽

2003 ◽

Vol 8 (3) ◽

pp. 131-147 ◽

Cited By ~ 43

Author(s):

Gian Vittorio Caprara ◽

Mariagiovanna Caprara ◽

Patrizia Steca

Keyword(s):

Personality Traits ◽

Adult Development ◽

Self Efficacy ◽

Age Groups ◽

Well Being ◽

Efficacy Beliefs ◽

Cross Sectional ◽

Education And Health ◽

Development And Aging ◽

And Gender

Three cross-sectional studies examined stability and change in personality over the course of life by measuring the relations linking age to personality traits, self-efficacy beliefs, values, and well-being in large samples of Italian male and female participants. In each study, relations between personality and age were examined across several age groups ranging from young adulthood to old age. In each study, personality constructs were first examined in terms of mean group differences accrued by age and gender and then in terms of their correlations with age across gender and age groups. Furthermore, personality-age correlations were also calculated, controlling for the demographic effects accrued by marital status, education, and health. Findings strongly indicated that personality functioning does not necessarily decline in the later years of life, and that decline is more pronounced in males than it is in females across several personality dimensions ranging from personality traits, such as emotional stability, to self-efficacy beliefs, such as efficacy in dealing with negative affect. Findings are discussed in terms of their implications for personality theory and social policy.

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