An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans.

TitleAn Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans.
Publication TypeJournal Article
Year of Publication2016
AuthorsReardon PKirkpatric, Clasen, iv L, Giedd JN, Blumenthal J, Lerch JP, M Chakravarty M, Raznahan A
JournalJ Neurosci
Volume36
Issue8
Pagination2438-48
Date Published2016 Feb 24
ISSN1529-2401
KeywordsAdolescent, Adult, Aneuploidy, Brain, Child, Child, Preschool, Cohort Studies, Corpus Striatum, Cross-Sectional Studies, Female, Gene Dosage, Globus Pallidus, Humans, Male, Sex Characteristics, Sex Chromosomes, Thalamus, Young Adult
Abstract

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings.

DOI10.1523/JNEUROSCI.3195-15.2016
Alternate JournalJ. Neurosci.
PubMed ID26911691
PubMed Central IDPMC4764663
Grant List / / Howard Hughes Medical Institute / United States
/ / Intramural NIH HHS / United States

  • Douglas Hospital
  • Dobell Pavillion
  • Brain imaging centre