Developmental Trajectories of Sex Differences in Negative Affect in Infants with FXS and at ASD Risk

Background: Research in Autism Spectrum Disorder (ASD) and fragile x syndrome (FXS) has predominantly focused on males due to sex differences in prevalence rates and increased phenotypic variability in females. Because temperament is relatively stable and accurately measured in infancy, it is a useful approach to understanding early developmental trajectories. Temperament has been linked to psycholobiological processes and systems, and thus may help identify early phenotypic markers of ASD that are tied to neurological or biological underpinnings. For example, a temperamental profile including higher negative affect has been shown to predict ASD in infant siblings (Garon et al., 2009).

There are reported sex differences in temperament in typically developing (TD) infants with girls rated higher on effortful control and boys higher on surgency, but no sex differences are observed in negative affect (Else-Quest, Hyde, & Goldsmith, 2006). However, no studies have examined sex differences in negative affect in infants at risk for FXS, and few have explored these questions in ASD. Because FXS is an X-chromosome linked, single-gene disorder associated with autism, it offers unique insight into the neurobiological sex differences in both disorders.

Objectives:  To assess the differences in initial level and change of negative affect from 12- to 18- and 24-months by sex and risk group.

Methods:  Participants included 109 infants assessed at 12, 18, and 24 months-of-age: 30 TD males, 25 ASIB males, 25 males with FXS, 9 TD females, 9 ASIB females, and 11 females with FXS. Most infants (n=94) had at least two data points. Parents completed the Infant Behavior Questionnaire at 12 months (IBQ; Rothbart, 1978) and the Early Childhood Behavior Questionnaire at 18-24 months (ECBQ; Putnam, Gartstein, & Rothbart, 2006).

Results:  A growth model using hierarchical linear modeling (HLM) centered at 12 months was performed. Results demonstrated a significant effect of age, with groups showing less parent-reported negative affect over time t(171) = -12.65, p <. 0001, d = 1.66. There was a marginal effect of risk group t(100) = -1.82, p = .07, suggesting that the FXS group had less negative affect than the ASIB and TD groups (ds > .3) who were not different from each other (d = .07). No sex differences were found.

Conclusions: This study was the first to examine sex differences in negative affect in infants with FXS and those with an older sibling with ASD. Consistent with earlier reports of these relationships TD infants, we found no sex differences in any risk group. This work suggests that existing conceptualizations about negative affect and its relation to ASD may be applicable to both males and females with these disorders. Further, the marginal effect risk group points to the possibility that profiles for predicting ASD may differ by etiological group, especially considering other work suggesting that negative affect is related to ASD symptoms in ASIB infants but anxiety in infants with FXS (Tonnsen, Malone, Hatton, & Roberts, 2013). Given the impact of early detection and intervention, it is important that early phenotypic characterizations of these disorders consider the impact of sex differences.