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Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain.

Published on Apr 1, 2018in Cerebral Cortex5.44
· DOI :10.1093/cercor/bhx040
Angelita Pui-Yee Wong3
Estimated H-index: 3
(U of T: University of Toronto),
Leon French14
Estimated H-index: 14
(U of T: University of Toronto)
+ 6 AuthorsTomáš Paus82
Estimated H-index: 82
Cite
Abstract
Abstract Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R2 = 0.46) and females (R2 = 0.30) and AR in males only (R2 = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-a-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R2 = 0.64; females: R2 = 0.58) but not high (males: R2 = 0.0045; females: R2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.
  • References (46)
  • Citations (8)
Cite
References46
Newest
Published on Jan 2, 2017in Journal of Neuroscience Research4.14
Tomáš Paus82
Estimated H-index: 82
(MIND Institute),
Angelita Pui-Yee Wong3
Estimated H-index: 3
(U of T: University of Toronto)
+ 1 AuthorsZdenka Pausova41
Estimated H-index: 41
(U of T: University of Toronto)
This Mini-Review describes sex differences in 66 quantitative characteristics of the brain and body measured in a community-based sample of 1,024 adolescents 12–18 years of age, members of the Saguenay Youth Study. Using an extensive phenotyping protocol, we have obtained measures in a number of domains, including brain structure, cognition, mental health, substance use, body composition, metabolism, cardiovascular reactivity, and life style. For each measure, we provide estimates of effect size...
Published on Jan 1, 2017in Neuroendocrinology6.80
Karen R. Mifsud7
Estimated H-index: 7
(UoB: University of Bristol),
Emily A. Saunderson5
Estimated H-index: 5
(UoB: University of Bristol)
+ 4 AuthorsJohannes M. H. M. Reul65
Estimated H-index: 65
(UoB: University of Bristol)
Background: Although glucocorticoid receptors (GRs) in the hippocampus play a vital role in the regulation of physiological and behavioural responses to stress, the regulation of receptor expression remains unclear. This work investigates the molecular mechanisms underpinning stress-induced changes in hippocampal GR mRNA levels in vivo. Methods: Male Wistar rats were killed either under baseline conditions or after forced swim stress (FSS; 15 min in 25°C water). Rat hippocampi were micro-dissect...
Published on Jun 1, 2016in Human Brain Mapping4.55
Veronica Popescu12
Estimated H-index: 12
(VUmc: VU University Medical Center),
Roel Klaver8
Estimated H-index: 8
(VUmc: VU University Medical Center)
+ 5 AuthorsHugo Vrenken48
Estimated H-index: 48
(VUmc: VU University Medical Center)
Grey matter (GM) atrophy is a prominent aspect of multiple sclerosis pathology and an important outcome in studies. GM atrophy measurement requires accurate GM segmentation. Several methods are used in vivo for measuring GM volumes in MS, but assessing their validity in vivo remains challenging. In this postmortem study, we evaluated the correlation between postmortem MRI cortical volume or thickness and the cortical thickness measured on histological sections. Sixteen MS brains were scanned in ...
Published on Mar 27, 2016in International Journal of Epidemiology7.34
Zdenka Pausova41
Estimated H-index: 41
,
Tomáš Paus82
Estimated H-index: 82
(MIND Institute)
+ 8 AuthorsJean R. Séguin43
Estimated H-index: 43
(UdeM: Université de Montréal)
The Saguenay Youth Study (SYS) is a two-generational study of adolescents and their parents (n = 1029 adolescents and 962 parents) aimed at investigating the aetiology, early stages and trans-generational trajectories of common cardiometabolic and brain diseases. The ultimate goal of this study is to identify effective means for increasing healthy life expectancy. The cohort was recruited from the genetic founder population of the Saguenay Lac St Jean region of Quebec, Canada. The participants u...
Published on Jan 1, 2016in Cerebral Cortex5.44
Inge K. Amlien20
Estimated H-index: 20
(University of Oslo),
Anders M. Fjell55
Estimated H-index: 55
(University of Oslo)
+ 5 AuthorsKristine B. Walhovd55
Estimated H-index: 55
(University of Oslo)
The human cerebral cortex undergoes a protracted, regionally heterogeneous development well into young adulthood. Cortical areas that expand the most during human development correspond to those that differ most markedly when the brains of macaque monkeys and humans are compared. However, it remains unclear to what extent this relationship derives from allometric scaling laws that apply to primate brains in general, or represents unique evolutionary adaptations. Furthermore, it is unknown whethe...
Published on Oct 23, 2015in Frontiers in Neuroscience3.65
Antonius Loonen12
Estimated H-index: 12
(UG: University of Groningen),
Svetlana A. Ivanova11
Estimated H-index: 11
(Tomsk Polytechnic University)
The very first free-moving animals in the oceans over 540 million years ago must have been able to obtain food, territory, and shelter, as well as reproduce. Therefore, they would have needed regulatory mechanisms to induce movements enabling achievement of these prerequisites for survival. It can be useful to consider these mechanisms in primitive chordates, which represent our earliest ancestors, to develop hypotheses addressing how these essential parts of human behavior are regulated and rel...
Published on Mar 24, 2015in PLOS ONE2.78
Janice L. Farlow5
Estimated H-index: 5
(IU: Indiana University Bloomington),
Hai Lin11
Estimated H-index: 11
(IU: Indiana University Bloomington)
+ 76 AuthorsPieter van der Vlies21
Estimated H-index: 21
(UG: University of Groningen)
Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, p...
Published on Mar 20, 2015in PLOS ONE2.78
Megan M. Herting19
Estimated H-index: 19
(Children's Hospital Los Angeles),
Prapti Gautam11
Estimated H-index: 11
(Children's Hospital Los Angeles)
+ 2 AuthorsElizabeth R. Sowell56
Estimated H-index: 56
(Children's Hospital Los Angeles)
Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year spa...
Published on Jan 1, 2015in Frontiers in Neuroscience3.65
Leon French14
Estimated H-index: 14
,
Tomáš Paus82
Estimated H-index: 82
(MIND Institute)
The Allen Human Brain Atlas provides an anatomically comprehensive view of gene expression in the brain (Hawrylycz et al., 2012). The complete transcriptome dataset consists of 58,692 measurements of gene expression in 3702 brain samples obtained from 6 individuals. The resulting product, over 200 million gene expression values, can be overwhelming for neuroscientists seeking to use the data. For example, data for a single gene consist of three interlinked files when downloaded from the Allen In...
Published on Dec 1, 2014in Cerebral Cortex5.44
I. Savic1
Estimated H-index: 1
,
Stefan Arver27
Estimated H-index: 27
(KI: Karolinska Institutet)
Although it has been shown that cortical thickness (Cth) differs between sexes, the underlying mechanisms are unknown. Seeing as XXY males have 1 extra X chromosome, we investigated the possible effects of Xand sex-chromosome dosage on Cth by comparing data from 31 XXY males with 39 XYand 47 XX controls. Plasma testosterone and estrogen were also measured in an effort to differentiate between possible sex-hormone and sex-chromosome gene effects. Cth was calculated with FreeSurfer software. Parie...
Cited By8
Newest
Published on Aug 28, 2018in Cerebral Cortex5.44
Y Patel (U of T: University of Toronto), Jean Shin6
Estimated H-index: 6
(U of T: University of Toronto)
+ 2 AuthorsTomáš Paus82
Estimated H-index: 82
(U of T: University of Toronto)
Published on Jun 26, 2019in Cerebral Cortex5.44
Nadine Parker1
Estimated H-index: 1
(U of T: University of Toronto),
Dídac Vidal-Piñeiro9
Estimated H-index: 9
(University of Oslo)
+ 29 AuthorsStefan Frenzel1
Estimated H-index: 1
Published on Apr 1, 2019in Genes, Brain and Behavior3.16
Shu Liu2
Estimated H-index: 2
(CAS: Chinese Academy of Sciences),
Ang Li2
Estimated H-index: 2
(CAS: Chinese Academy of Sciences)
+ 2 AuthorsBing LiuLingzhong FanYue23
Estimated H-index: 23
Published on Dec 1, 2018in Scientific Reports4.01
Liesa Ilg1
Estimated H-index: 1
(TUD: Dresden University of Technology),
Manousos A. Klados14
Estimated H-index: 14
(TUD: Dresden University of Technology)
+ 2 AuthorsShu-Chen Li50
Estimated H-index: 50
(TUD: Dresden University of Technology)
The fetus is highly responsive to the level of glucocorticoids in the gestational environment. Perturbing glucocorticoids during fetal development could yield long-term consequences. Extending prior research about effects of prenatally exposed synthetic glucocorticoids (sGC) on brain structural development during childhood, we investigated functional brain correlates of cognitive conflict monitoring in term-born adolescents, who were prenatally exposed to sGC. Relative to the comparison group, b...
Published on Sep 1, 2018in Cerebral Cortex5.44
Jean Shin6
Estimated H-index: 6
(U of T: University of Toronto),
Leon French14
Estimated H-index: 14
(U of T: University of Toronto)
+ 7 AuthorsTomáš Paus82
Estimated H-index: 82
Published on Dec 1, 2017in Scientific Reports4.01
Nadine Parker1
Estimated H-index: 1
(U of T: University of Toronto),
Angelita Pui-Yee Wong3
Estimated H-index: 3
(U of T: University of Toronto)
+ 6 AuthorsTomáš Paus82
Estimated H-index: 82
Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regiona...
Published on Nov 14, 2017in Frontiers in Human Neuroscience2.87
Maiko Abel Schneider3
Estimated H-index: 3
(UFRGS: Universidade Federal do Rio Grande do Sul),
Poli Mara Spritzer29
Estimated H-index: 29
(UFRGS: Universidade Federal do Rio Grande do Sul)
+ 9 AuthorsMauricio Anés7
Estimated H-index: 7
Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing psychological suffering that accompanies the incongruence between one's experienced or expressed gender and one's assigned gender. Manifestation of GD can be seen early on during childhood and adolescence. During this period, the development of undesirable sexual characteristics marks an acute suffering of being opposite to the sex of birth. Pubertal suppression with gonadotropin releasing hormone analogs (GnRHa) has...
Published on Dec 1, 2017in NeuroImage5.81
Rafael Romero-Garcia13
Estimated H-index: 13
(University of Cambridge),
Kirstie J. Whitaker12
Estimated H-index: 12
(University of Cambridge)
+ 8 AuthorsPetra E. Vértes22
Estimated H-index: 22
(University of Cambridge)
Abstract Complex network topology is characteristic of many biological systems, including anatomical and functional brain networks (connectomes). Here, we first constructed a structural covariance network from MRI measures of cortical thickness on 296 healthy volunteers, aged 14–24 years. Next, we designed a new algorithm for matching sample locations from the Allen Brain Atlas to the nodes of the SCN. Subsequently we used this to define, transcriptomic brain networks by estimating gene co-expre...
View next paperA FreeSurfer view of the cortical transcriptome generated from the Allen Human Brain Atlas.