Commentary: sex difference differences? A reply to Constantino.

Jana M. Iverson,Alice Carter,Ted Hutman,Charles A. Nelson,Gregory S. Young,Tony Charman,Wendy L. Stone,Karen Dobkins,Suzanne Curtin,Sally Ozonoff,Lonnie Zwaigenbaum,Rebecca Landa,Irva Hertz-Picciotto,Daniel S. Messinger,Katarzyna Chawarska,Sara Jane Webb,Susan E. Bryson,Leslie Carver,Helen Tager-Flusberg

doi:10.1186/s13229-016-0093-9

Abstract

Messinger et al. found a 3.18 odds ratio of male to female ASD recurrence in 1241 prospectively followed high-risk (HR) siblings. Among high-risk siblings (with and without ASD), as well as among 583 low-risk controls, girls exhibited higher performance on the Mullen Scales of Early Learning, as well as lower restricted and repetitive behavior severity scores on the Autism Diagnostic Observation Schedule (ADOS) than boys. That is, female-favoring sex differences in developmental performance and autism traits were evident among low-risk and non-ASD high-risk children, as well as those with ASD. Constantino (Mol Autism) suggests that sex differences in categorical ASD outcomes in Messinger et al. should be understood as a female protective effect. We are receptive to Constantino’s (Mol Autism) suggestion, and propose that quantitative sex differences in autism-related features are keys to understanding this female protective effect.

Highlights

Prospective studies of the high-risk siblings of children with autism spectrum disorder (ASD) offer an opportunity to examine both sex differences in ASD occurrence and sex differences in ASD traits and related cognitive characteristics
The female protective effect may be operationalized with respect to the Carter effect, which holds that siblings of female ASD probands will evidence greater ASD affectation than siblings of male probands [2, 3]
Constantino suggests that sex differences in categorical ASD clinical outcomes among the high-risk siblings themselves should be understood as a female protective effect [5]

Summary

Background

Prospective studies of the high-risk siblings of children with ASD offer an opportunity to examine both sex differences in ASD occurrence and sex differences in ASD traits and related cognitive characteristics. The female protective effect may be operationalized with respect to the Carter effect, which holds that siblings of female ASD probands will evidence greater ASD affectation (more severe autism traits) than siblings of male probands [2, 3]. This argument has been buttressed by findings of increased genetic liability (e.g., deleterious copy number variants and single-nucleotide variants) in. Constantino suggests that sex differences in categorical ASD clinical outcomes among the high-risk siblings themselves should be understood as a female protective effect [5]. The proportion of HR siblings with ASD outcomes was .27 (193/714) for males and .11 (59/527) for females (see Fig. 1)

Conclusions

Messinger DS et al Early sex differences are not autism-specific: a Baby