Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain

Witte, A. Veronica; Savli, Markus; Holik, A.; Kasper, Siegfried; Lanzenberger, Rupert

doi:10.1016/j.neuroimage.2009.09.046

Cited by 142 publications

(126 citation statements)

References 78 publications

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“…Sex brain dimorphism includes brain size, white and gray matter volume and regional cortical thickness changes. [34][35][36] This study did not reveal significant differences in brain size between patients with KS and controls. Moreover, sex-and testosterone-related brain differences do not seem to involve the medial orbital-frontal basal regions, thus restraining the direct role of hormonal dysfunction in determining the morphologic pattern observed in patients with KS.…”

Section: Discussioncontrasting

confidence: 63%

Brain Changes in Kallmann Syndrome

Manara

Salvalaggio

Favaro³

et al. 2014

American Journal of Neuroradiology

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BACKGROUND AND PURPOSE:Kallmann syndrome is a rare inherited disorder due to defective intrauterine migration of olfactory axons and gonadotropin-releasing hormone neurons, leading to rhinencephalon hypoplasia and hypogonadotropic hypogonadism. Concomitant brain developmental abnormalities have been described. Our aim was to investigate Kallmann syndrome-related brain changes with conventional and novel quantitative MR imaging analyses.

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Section: Discussioncontrasting

confidence: 63%

Brain Changes in Kallmann Syndrome

Manara

Salvalaggio

Favaro³

et al. 2014

American Journal of Neuroradiology

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“…To date, attempts to relate testosterone signaling to brain anatomy in humans have relied on interindividual differences in serum testosterone levels (that are hard to acquire with high reliability; ref. 19), and used crosssectional study designs that have factored out the effects of age (20,22) and/or sex (21). Therefore, our focus on genetically determined variation in androgen receptor functioning within a longitudinal study of adolescent cortical thickness change provides some of the strongest evidence to date that androgen signaling has the capacity to influence neurodevelopmental processes in humans.…”

Section: Genetic Variation Conferring Enhanced Androgen Receptor Effimentioning

confidence: 99%

“…This lack of knowledge is partly a result of the absence of any spatially detailed longitudinal characterization of what constitutes "masculinization" of cortical maturation in humans, but also reflects the challenges of accurately (19) and repeatedly measuring serum androgens in large longitudinal cohorts-especially during adolescence, when surging androgen levels make the question of androgen receptor-mediated influences on brain development highly relevant. The few studies that have attempted to relate circulating androgens to brain anatomy in humans are cross-sectional in design, and have generated mixed results (20)(21)(22), although the largest of these studies report that possession of a genetic variant conferring more efficient androgen receptor functioning strengthens the relationship between peripheral measures of testosterone and brain anatomy (23,24).…”

mentioning

confidence: 99%

Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence

Raznahan

Lee

Stidd

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

246

197

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Humans have systematic sex differences in brain-related behavior, cognition, and pattern of mental illness risk. Many of these differences emerge during adolescence, a developmental period of intense neurostructural and endocrine change. Here, by creating "movies" of sexually dimorphic brain development using longitudinal in vivo structural neuroimaging, we show regionally specific sex differences in development of the cerebral cortex during adolescence. Within cortical subsystems known to underpin domains of cognitive behavioral sex difference, structural change is faster in the sex that tends to perform less well within the domain in question. By stratifying participants through molecular analysis of the androgen receptor gene, we show that possession of an allele conferring more efficient functioning of this sex steroid receptor is associated with "masculinization" of adolescent cortical maturation. Our findings extend models first established in rodents, and suggest that in humans too, sex and sex steroids shape brain development in a spatiotemporally specific manner, within neural systems known to underpin sexually dimorphic behaviors.

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“…Previous research suggests that sex hormones may present differential patterns of associations with distinct brain regions — including ones that are related to dementia – and with specific brain functions (Holland et al., 2011; Lessov‐Schlaggar et al., 2005; Peper & Koolschijn, 2012; Witte, Savli, Holik, Kasper, & Lanzenberger, 2010). We therefore examined both global and regional GM and white matter (WM) volumes to identify brain regions that may be differently related to T and SHBG levels in middle‐age men; in secondary analyses, we assessed the relationship of T and SHBG levels with three components of cognitive performance: psychomotor speed, verbal memory, and executive function.…”

Section: Introductionmentioning

confidence: 99%

Sex hormones and brain volumes in a longitudinal study of middle‐aged men in the CARDIA study

et al. 2017

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IntroductionSeveral findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle‐age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle‐aged men. We also evaluated the association of sex hormone levels with cognitive function.MethodsAnalysis included 267 community‐dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2nd to 4th decade of life; brain volumes were measured at the ages of 42–56. Associations were estimated using linear regression models, adjusted for several potential confounders.ResultsHigher SHBG levels were associated with greater total WM volume (+3.15 cm3 [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (−0.96 cm3 [95%CI = −1.71, −0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function.ConclusionResults suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.

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Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain

Cited by 142 publications

References 78 publications

Brain Changes in Kallmann Syndrome

Brain Changes in Kallmann Syndrome

Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence

Sex hormones and brain volumes in a longitudinal study of middle‐aged men in the CARDIA study

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