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J Neurosci. 2016 Feb 24;36(8):2438-48. doi: 10.1523/JNEUROSCI.3195-15.2016.

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

Author information

1
Developmental Neurogenomics Unit, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, kirk.reardon@nih.gov.
2
Developmental Neurogenomics Unit, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
3
Department of Psychiatry, University of California San Diego, San Diego, California 92093.
4
Department of Psychiatry and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5T 1R8, Canada.
5
Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec H4H 1R3, Canada, and Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec H3A 1A1, Canada.

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.

KEYWORDS:

allometry; aneuploidy; morphometry; sex; subcortex

PMID:
26911691
PMCID:
PMC4764663
DOI:
10.1523/JNEUROSCI.3195-15.2016
[Indexed for MEDLINE]
Free PMC Article

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