Between-sex differences not greater than within-sex differences in early adolescent brain structure
Poster No:
1247
Submission Type:
Abstract Submission
Authors:
Carinna Torgerson1, Hedyeh Ahmadi1, Megan Herting1, Jeiran Choupan1
Institutions:
1University of Southern California, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
Neuroimaging studies of sex differences in the pediatric human brain predominantly examine mean differences between males and females (Giedd et al., 2012; Giedd & Denker, 2015; Kaczkurkin et al., 2019; Lenroot & Giedd, 2010). Yet, during development, inter-individual variability in brain structure is high (Bottenhorn et al., 2023). Significant sex differences in variance have also been reported in children and adolescents (Bottenhorn et al., 2023; Forde et al., 2020; Wierenga et al., 2018). Unequal variance between groups violates the assumptions of many of the traditional statistical methods for evaluating sex differences - such as ANOVA and t-tests. Without investigating the amount of individual variability within sexes, we cannot say definitively whether the mean differences actually reflect distinct male and female phenotypes (e.g., sexual dimorphism) of the brain.
Methods:
We aimed to characterize the relationship between sex and brain macro- and micro-structure in early adolescence using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=8,272). To do so, we examined homogeneity of variance between sexes, overlap between male and female distributions, and performed an analysis of similarities (ANOSIM) on global metrics of brain structure. For completeness, we performed all statistical tests using both uncorrected (raw) measures of brain structure and after correcting for age, pubertal development, socioeconomic status, race, ethnicity, and MRI scanner manufacturer.
Results:
Although mean sex differences were significant in the mixed-effects models of total brain volume, average cortical thickness, and whole-brain mean diffusivity, there was more overlap than difference between male and female distributions for all measurements (Figure 1). Furthermore, we found significant sex differences in variance of total brain volume and mean diffusivity. ANOSIM results showed that within-sex and between-sex variance were similar for all measures.
Conclusions:
We found high similarity and low difference between sexes on four common measures of adolescent brain structure. In particular, the ANOSIM results suggest that two random adolescents of the same sex will differ as much as a random female and random male differ. In conjunction with our finding of significant inhomogeneity of variance between males and females, these findings suggest that reported sex differences in global measures of early adolescent brain structure are likely driven by disparities in variance, rather than distinctive sex-based phenotypes. Such results contradict previous reports of consistent, meaningful sex differences in total brain volume throughout the lifespan (Giedd et al., 1997, 2015; Lenroot et al., 2007), but support studies which have found significant variance sex differences in brain structure (Bottenhorn et al., 2023; Forde et al., 2020; Wierenga et al., 2018). The findings also serve as a reminder that aggregate differences should not be applied to inter-individual comparisons.
Lifespan Development:
Early life, Adolescence, Aging 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Normal Development 2
Keywords:
Development
MRI
NORMAL HUMAN
Sexual Dimorphism
Statistical Methods
Other - variance
1|2Indicates the priority used for review
Provide references using author date format
Forde, N. J. (2020). Sex Differences in Variability of Brain Structure Across the Lifespan. Cerebral Cortex, 30(10), 5420–5430. https://doi.org/10.1093/cercor/bhaa123
Giedd, J. N. (1997). Sexual dimorphism of the developing human brain. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 21(8), 1185–1201. https://doi.org/10.1016/s0278-5846(97)00158-9
Giedd, J. N. (2012). Magnetic resonance imaging of male/female differences in human adolescent brain anatomy. Biology of Sex Differences, 3(1), 1–9.
Giedd, J. N. (2015). The Adolescent Brain: Insights from Neuroimaging. In: Brain Crosstalk in Puberty and Adolescence (pp. 85–96). Springer International Publishing. https://doi.org/10.1007/978-3-319-09168-6_7
Kaczkurkin, A. N. (2019). Sex differences in the developing brain: Insights from multimodal neuroimaging. Neuropsychopharmacology, 44(1), 71–85. https://doi.org/10.1038/s41386-018-0111-z
Lenroot, R. K. (2007). Sexual dimorphism of brain developmental trajectories during childhood and adolescence. Neuroimage, 36(4), 1065–1073.
Lenroot, R. K. (2010). Sex differences in the adolescent brain. Brain and Cognition, 72(1), 46–55.
Wierenga, L. M. (2018). A key characteristic of sex differences in the developing brain: Greater variability in brain structure of boys than girls. Cerebral Cortex, 28(8), 2741–2751.