Advancing paternal age and simplex autism

Department of Pshychology, Temple University, Philadelphia, PA 19122, USA.
Autism (Impact Factor: 3.5). 12/2011; 16(4):367-80. DOI: 10.1177/1362361311427154
Source: PubMed


De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling for maternal age, results support a significant interaction of linear paternal age and sex of the child on simplex family type. Female ASD cases were significantly more likely to be simplex as paternal age increased, but the increase for males was not significant. Findings suggest that ASD arising from non-familial, de novo events may be far less prominent in males than in females, even if more prevalent in males, due to the substantially larger number of male cases attributable to other, more strongly male-biased risk factors.

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    • "This awaits future studies employing a similar design as ours. The sex-specific neuroanatomy discovered here for high-functioning adults with autism are in line with the growing evidence of sex-specific biological profiles for the high-functioning subgroup at the levels of serum proteomics (Schwarz et al., 2011; Ramsey et al., 2012), sex steroid hormones and anthropometry (Ruta et al., 2011; Bejerot et al., 2012), and for the whole autism spectrum at the levels of genetics (Gilman et al., 2011; Puleo et al., 2012; Szatmari et al., 2012), transcriptomics (Kong et al., 2012) and early brain overgrowth (Sparks et al., 2002; Bloss and Courchesne, 2007; Schumann et al., 2009, 2010; Nordahl et al., 2011). In sum, high-functioning males and females with autism, though diagnosed by the same behavioural criteria, differ in aspects of neuroanatomy. "
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    ABSTRACT: In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the 'extreme male brain' theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P < 0.001) overlapped with areas that were sexually dimorphic in neurotypical controls, in both grey and white matter, suggesting neural 'masculinization'. This was not seen in males with autism. How differences in neuroanatomy relate to the similarities in cognition between males and females with autism remains to be understood. Future research should stratify by biological sex to reduce heterogeneity and to provide greater insight into the neurobiology of autism.
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    ABSTRACT: In 1996, a practice guideline on genetic counseling for advanced paternal age was published. The current document updates the state of knowledge of advanced paternal age effects on single gene mutations, chromosome anomalies, and complex traits.
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    ABSTRACT: Mary Cannon discusses the implications of a new cohort study showing an association between increasing paternal age and poorer cognitive abilities in the offspring.
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