Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.

Original languageEnglish (US)
Article number32
JournalMolecular Autism
Volume6
Issue number1
DOIs
StatePublished - Jun 4 2015

Fingerprint

Autistic Disorder
Sex Characteristics
Siblings
Research
Learning
Appointments and Schedules
Observation
Recurrence
Neurobehavioral Manifestations
Autism Spectrum Disorder
Linear Models
Odds Ratio
Language

Keywords

  • Development
  • High-risk siblings
  • Longitudinal
  • Sex differences
  • Symptom severity

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental Neuroscience
  • Developmental Biology
  • Molecular Biology

Cite this

Messinger, D. S., Young, G. S., Webb, S. J., Ozonoff, S. J., Bryson, S. E., Carter, A., ... Zwaigenbaum, L. (2015). Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Molecular Autism, 6(1), [32]. https://doi.org/10.1186/s13229-015-0027-y

Early sex differences are not autism-specific : A Baby Siblings Research Consortium (BSRC) study. / Messinger, Daniel S.; Young, Gregory S.; Webb, Sara Jane; Ozonoff, Sally J; Bryson, Susan E.; Carter, Alice; Carver, Leslie; Charman, Tony; Chawarska, Katarzyna; Curtin, Suzanne; Dobkins, Karen; Hertz-Picciotto, Irva; Hutman, Ted; Iverson, Jana M.; Landa, Rebecca; Nelson, Charles A.; Stone, Wendy L.; Tager-Flusberg, Helen; Zwaigenbaum, Lonnie.

In: Molecular Autism, Vol. 6, No. 1, 32, 04.06.2015.

Research output: Contribution to journalArticle

Messinger, DS, Young, GS, Webb, SJ, Ozonoff, SJ, 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 2015, 'Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study', Molecular Autism, vol. 6, no. 1, 32. https://doi.org/10.1186/s13229-015-0027-y
Messinger, Daniel S. ; Young, Gregory S. ; Webb, Sara Jane ; Ozonoff, Sally J ; Bryson, Susan E. ; Carter, Alice ; Carver, Leslie ; Charman, Tony ; Chawarska, Katarzyna ; Curtin, Suzanne ; Dobkins, Karen ; Hertz-Picciotto, Irva ; Hutman, Ted ; Iverson, Jana M. ; Landa, Rebecca ; Nelson, Charles A. ; Stone, Wendy L. ; Tager-Flusberg, Helen ; Zwaigenbaum, Lonnie. / Early sex differences are not autism-specific : A Baby Siblings Research Consortium (BSRC) study. In: Molecular Autism. 2015 ; Vol. 6, No. 1.
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abstract = "Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 {\%} and female recurrence 10.3 {\%}, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.",
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T1 - Early sex differences are not autism-specific

T2 - A Baby Siblings Research Consortium (BSRC) study

AU - Messinger, Daniel S.

AU - Young, Gregory S.

AU - Webb, Sara Jane

AU - Ozonoff, Sally J

AU - Bryson, Susan E.

AU - Carter, Alice

AU - Carver, Leslie

AU - Charman, Tony

AU - Chawarska, Katarzyna

AU - Curtin, Suzanne

AU - Dobkins, Karen

AU - Hertz-Picciotto, Irva

AU - Hutman, Ted

AU - Iverson, Jana M.

AU - Landa, Rebecca

AU - Nelson, Charles A.

AU - Stone, Wendy L.

AU - Tager-Flusberg, Helen

AU - Zwaigenbaum, Lonnie

PY - 2015/6/4

Y1 - 2015/6/4

N2 - Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.

AB - Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis.

KW - Development

KW - High-risk siblings

KW - Longitudinal

KW - Sex differences

KW - Symptom severity

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