Comment

. 2016 Jun 29:7:31.

doi: 10.1186/s13229-016-0093-9. eCollection 2016.

Commentary: sex difference differences? A reply to Constantino

Daniel S Messinger¹, Gregory S Young², Sara Jane Webb³, Sally Ozonoff², Susan E Bryson⁴, Alice Carter⁵, Leslie Carver⁶, Tony Charman⁷, Katarzyna Chawarska⁸, Suzanne Curtin⁹, Karen Dobkins⁶, Irva Hertz-Picciotto², Ted Hutman¹⁰, Jana M Iverson¹¹, Rebecca Landa¹², Charles A Nelson¹³, Wendy L Stone¹⁴, Helen Tager-Flusberg¹⁵, Lonnie Zwaigenbaum¹⁶

Affiliations

¹ University of Miami, Coral Gables, USA.
² University of California, Davis, Davis, USA.
³ Seattle Children's Research Institute, Seattle, USA ; University of Washington, Seattle, USA.
⁴ Izaak Walton Killam Health Centre, Halifax, Canada ; Dalhousie University, Halifax, Canada.
⁵ University of Massachusetts, Boston, Boston, USA.
⁶ University of California, San Diego, La Jolla, USA.
⁷ King's College London, London, UK.
⁸ Yale University School of Medicine, New Haven, USA.
⁹ University of Calgary, Calgary, Canada.
¹⁰ University of California, Los Angeles, Los Angeles, USA.
¹¹ University of Pittsburgh, Pittsburgh, USA.
¹² Kennedy Krieger Institute, Baltimore, USA ; John Hopkins School of Medicine, Baltimore, USA.
¹³ Harvard Medical School, Boston, USA ; Harvard Graduate School of Education, Cambridge, USA ; Boston Children's Hospital, Boston, USA.
¹⁴ University of Washington, Seattle, USA.
¹⁵ Boston University, Boston, USA.
¹⁶ University of Alberta, Edmonton, Canada.

PMID: 27358719
PMCID: PMC4926305
DOI: 10.1186/s13229-016-0093-9

Comment

Commentary: sex difference differences? A reply to Constantino

Daniel S Messinger et al. Mol Autism. 2016.

. 2016 Jun 29:7:31.

doi: 10.1186/s13229-016-0093-9. eCollection 2016.

Authors

Affiliations

¹ University of Miami, Coral Gables, USA.
² University of California, Davis, Davis, USA.
³ Seattle Children's Research Institute, Seattle, USA ; University of Washington, Seattle, USA.
⁴ Izaak Walton Killam Health Centre, Halifax, Canada ; Dalhousie University, Halifax, Canada.
⁵ University of Massachusetts, Boston, Boston, USA.
⁶ University of California, San Diego, La Jolla, USA.
⁷ King's College London, London, UK.
⁸ Yale University School of Medicine, New Haven, USA.
⁹ University of Calgary, Calgary, Canada.
¹⁰ University of California, Los Angeles, Los Angeles, USA.
¹¹ University of Pittsburgh, Pittsburgh, USA.
¹² Kennedy Krieger Institute, Baltimore, USA ; John Hopkins School of Medicine, Baltimore, USA.
¹³ Harvard Medical School, Boston, USA ; Harvard Graduate School of Education, Cambridge, USA ; Boston Children's Hospital, Boston, USA.
¹⁴ University of Washington, Seattle, USA.
¹⁵ Boston University, Boston, USA.
¹⁶ University of Alberta, Edmonton, Canada.

PMID: 27358719
PMCID: PMC4926305
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.

Keywords: Autism spectrum disorder; Female protective effect; High-risk siblings; Sex differences.

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Figures

**Fig. 1**
ASD symptoms and ASD recurrence by sex in high-risk siblings with and without ASD. *Horizontal lines* indicate differences between male and female high-risk siblings in ADOS Restricted and Repetitive Behavior (RRB) severity scores [1]. The *vertical arrows* connect high-risk No-ASD and to high-risk ASD groups (see Constantino, 2016, Figure 1). The widths of the *upward arrows* reflect the proportion of high-risk males (.27) and the proportion of HR females (.11) with an ASD outcome. These proportions are also reflected in the width of the *horizontal lines* of male and female ASD groups

See this image and copyright information in PMC

Comment on

Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study.
Messinger DS, Young GS, Webb SJ, Ozonoff S, Bryson SE, Carter A, Carver L, Charman T, Chawarska K, Curtin S, Dobkins K, Hertz-Picciotto I, Hutman T, Iverson JM, Landa R, Nelson CA, Stone WL, Tager-Flusberg H, Zwaigenbaum L. Messinger DS, et al. Mol Autism. 2015 Jun 4;6:32. doi: 10.1186/s13229-015-0027-y. eCollection 2015. Mol Autism. 2015. PMID: 26045943 Free PMC article.
Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al.
Constantino JN. Constantino JN. Mol Autism. 2016 Jun 29;7:32. doi: 10.1186/s13229-016-0092-x. eCollection 2016. Mol Autism. 2016. PMID: 27358720 Free PMC article.

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Fan H, Hou Y, Sahana G, Gao H, Zhu C, Du L, Zhao F, Wang L. Fan H, et al. Animals (Basel). 2019 Sep 5;9(9):655. doi: 10.3390/ani9090655. Animals (Basel). 2019. PMID: 31491862 Free PMC article.

References

1. Messinger DS, et al. Early sex differences are not autism-specific: a Baby Siblings Research Consortium (BSRC) study. Mol Autism. 2015;6:32. doi: 10.1186/s13229-015-0027-y. - DOI - PMC - PubMed
1. Robinson EB, et al. Examining and interpreting the female protective effect against autistic behavior. Proc Natl Acad Sci U S A. 2013;110(13):5258–62. doi: 10.1073/pnas.1211070110. - DOI - PMC - PubMed
1. Jacquemont S, et al. A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. Am J Hum Genet. 2014;94(3):415–25. doi: 10.1016/j.ajhg.2014.02.001. - DOI - PMC - PubMed
1. Jacquemont S, Coe BP, Hersch M, Duyzend MH, Krumm N, Bergmann S, Eichler EE (2014). A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders. Am J Hum Genet. 2014;94(3):415-425. doi: 10.1016/j.ajhg.2014.02.001 - PMC - PubMed
1. Constantino JN. Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: a commentary on Messinger et al. Mol Autism. 2016. In press. - PMC - PubMed

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Commentary: sex difference differences? A reply to Constantino

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