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Background <p>Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism.</p> Methods <p>Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were compared across groups using analysis of variance. Between-parent and within-parent correlations across trait domains examined patterns of familial trait aggregation and assessed shared versus unique contributions to the inheritance of autism. Logistic regression assessed the predictive utility of parental traits for simplex vs. multiplex group membership.</p> Results <p>Mean levels of paternal autistic traits (F(2, 224) = 5.67, FDR-adjusted p-value (q) = 0.013) and maternal anxious (F(2, 262) = 11.14, q &lt; 0.001) and depressive (F(2, 262) = 7.08, q = 0.005) traits differed between groups. Post-hoc tests revealed elevated autistic traits in multiplex fathers (q = 0.009) and elevated anxious (q &lt; 0.001) and depressive (q = 0.004) traits in multiplex mothers compared to parents of non-autistic children; simplex parents did not differ from either of the other groups. Parental traits jointly accounted for 7.9% of autism recurrence liability in multiplex families. Elevations in autistic traits co-occur with elevations in neuropsychiatric traits in simplex parents (0.35 ≤ <i>r</i> ≤ 0.43) but were uncorrelated in multiplex parents.</p> Limitations <p>Findings from this study may not generalize to more heterogeneous samples with differing racial, ethnic, and socioeconomic demographics. Exclusionary criteria for the original study may result in families with a lower trait burden for psychiatric disorders than the broader population of parents of autistic children.</p> Conclusions <p>Results highlight unique patterns of autistic, anxious, and depressive trait presentation and aggregation in multiplex parents. Findings call for a transdiagnostic approach to quantifying genetic liability in families with autistic children.</p>

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Subclinical neuropsychiatric trait variation in parents of children with autism spectrum disorder: a cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月15日

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  • Lindsay J. Mullin,
  • Kai Xia,
  • Jeffrey Wang,
  • Chimei M. Lee,
  • Tessa G. Buscher,
  • Carolyn Lasch,
  • Catherine A. Burrows,
  • Jed T. Elison,
  • Mark D. Shen,
  • Steven R. Dager,
  • Annette M. Estes,
  • Heather C. Hazlett,
  • Natasha Marrus,
  • Juhi Pandey,
  • Robert T. Schultz,
  • Tanya St. John,
  • Lonnie Zwaigenbaum,
  • John N. Constantino,
  • Joseph Piven,
  • Jessica B. Girault

摘要

Background

Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism.

Methods

Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were compared across groups using analysis of variance. Between-parent and within-parent correlations across trait domains examined patterns of familial trait aggregation and assessed shared versus unique contributions to the inheritance of autism. Logistic regression assessed the predictive utility of parental traits for simplex vs. multiplex group membership.

Results

Mean levels of paternal autistic traits (F(2, 224) = 5.67, FDR-adjusted p-value (q) = 0.013) and maternal anxious (F(2, 262) = 11.14, q < 0.001) and depressive (F(2, 262) = 7.08, q = 0.005) traits differed between groups. Post-hoc tests revealed elevated autistic traits in multiplex fathers (q = 0.009) and elevated anxious (q < 0.001) and depressive (q = 0.004) traits in multiplex mothers compared to parents of non-autistic children; simplex parents did not differ from either of the other groups. Parental traits jointly accounted for 7.9% of autism recurrence liability in multiplex families. Elevations in autistic traits co-occur with elevations in neuropsychiatric traits in simplex parents (0.35 ≤ r ≤ 0.43) but were uncorrelated in multiplex parents.

Limitations

Findings from this study may not generalize to more heterogeneous samples with differing racial, ethnic, and socioeconomic demographics. Exclusionary criteria for the original study may result in families with a lower trait burden for psychiatric disorders than the broader population of parents of autistic children.

Conclusions

Results highlight unique patterns of autistic, anxious, and depressive trait presentation and aggregation in multiplex parents. Findings call for a transdiagnostic approach to quantifying genetic liability in families with autistic children.