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Review
. 2014 Feb;39(100):34-50.
doi: 10.1016/j.neubiorev.2013.12.004. Epub 2013 Dec 26.

A meta-analysis of sex differences in human brain structure

Amber N V Ruigrok  1 , Gholamreza Salimi-Khorshidi  2 , Meng-Chuan Lai  3 , Simon Baron-Cohen  4 , Michael V Lombardo  5 , Roger J Tait  6 , John Suckling  7
Affiliations
Review

A meta-analysis of sex differences in human brain structure

Amber N V Ruigrok et al. Neurosci Biobehav Rev. 2014 Feb.

Abstract

The prevalence, age of onset, and symptomatology of many neuropsychiatric conditions differ between males and females. To understand the causes and consequences of sex differences it is important to establish where they occur in the human brain. We report the first meta-analysis of typical sex differences on global brain volume, a descriptive account of the breakdown of studies of each compartmental volume by six age categories, and whole-brain voxel-wise meta-analyses on brain volume and density. Gaussian-process regression coordinate-based meta-analysis was used to examine sex differences in voxel-based regional volume and density. On average, males have larger total brain volumes than females. Examination of the breakdown of studies providing total volumes by age categories indicated a bias towards the 18-59 year-old category. Regional sex differences in volume and tissue density include the amygdala, hippocampus and insula, areas known to be implicated in sex-biased neuropsychiatric conditions. Together, these results suggest candidate regions for investigating the asymmetric effect that sex has on the developing brain, and for understanding sex-biased neurological and psychiatric conditions.

Keywords: Brain; Gaussian-process regression (GPR); Meta-analysis; Sex differences; Volume; Voxel-based morphometry.

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Figures

Fig. 1
Fig. 1
Flow diagram based on PRISMA statement (www.prisma-statement.org).
Fig. 2
Fig. 2
Forest plot for the grey matter volume meta-analysis. Overview of all studies included in the grey matter volume meta-analysis. The square indicates the effect size in mL of each study (i.e. the difference in mL volume between males and females) and the bars indicate the 95% confidence interval of each study. The studies corresponding to the effect size can be found on the left. Study IDs correspond to the study IDs in Table 1. The diamond at the bottom of the figure indicates the meta-analytic effect size and its variance.
Fig. 3
Fig. 3
Breakdown by age categories for reports providing intracranial volume and grey matter volume. Three plots display the breakdown of studies examining intracranial volume (ICV) and grey matter volume (GM) in the current literature across six age categories: ‘infant’ (0–1 years), ‘early childhood’ (2–6 years), ‘late childhood’ (7–17 years), ‘mature’ (18–59 years), ‘senior’ (60+ years), and ‘lifespan’ (any study covering more than 2 age ranges): (a) the total number of articles providing ICV in each age category; (b) the sum of the total number of male and female participants included in those age categories; and (c) displays the weighted mean volumes of ICV and weighted error bars for males and females across all age categories. (d) The total number of articles providing GM in each age category; (e) the sum of the total number of male and female participants included in those age categories; and (f) displays the weighted mean volumes of GM and weighted error bars for males and females across all age categories.
Fig. 4
Fig. 4
Voxel-based regional sex differences in grey matter volume. Female > Male in red, and Male > Female is in blue. Panel a, rendered overview of uncorrected regional sex differences in grey matter volume. All other panels are thresholded at FDR q < 0.01. Panels b–f display areas of larger volume in females (red) including (b) the right inferior and middle frontal gyri, pars triangularis and planum temporale; (c) thalamus and right anterior cingulate gyrus; and (f) left and right thalamus; and areas of larger volume in males (blue), including (c) the anterior cingulate gyrus; (d) bilateral posterior cingulate gyrus and precuneus and left cerebellum; (e) anterior and posterior cingulate gyri; and (f) left and right amygdalae, hippocampi and parahippocampal gyri.
Fig. 5
Fig. 5
Voxel-based regional sex differences in grey matter density. Female > Male in red, and Male > Female is in blue. Panel a, rendered overview of uncorrected regional sex differences in grey matter concentration. All other panels are thresholded at FDR q < 0.05. Panels b–c display areas of larger volume in females (red) in (b) frontal pole and (c) right thalamus; and in males (blue) including (c) left amygdala, hippocampus, insular cortex and putamen; (d) right and left cerebellum VI lobe.
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