Infant Temperament in the FMR1 Premutation and Fragile X Syndrome

Abstract

Although temperament has been studied for decades as a predictor of psychopathology in the general population, examining temperament in neurogenetic groups has unique potential to inform the genetic and biological factors that may confer risk for psychopathology in later development. The present study examined early temperament in two heritable neurogenetic conditions associated with atypical CGG repeat expansions on the FMR1 gene: the FMR1 premutation (FXpm; 55-200 repeats) and fragile X syndrome (FXS; >200 repeats). We focus specifically on the FXpm, as the condition is highly prevalent (1:209 females and 1:430 males) and associated with increased risk for pediatric psychopathology, including attention problems, autism, and anxiety. In contrast, FXS is a low-incidence disorder (1:4,000) often associated with intellectual disability and more severe co-occurring psychosocial conditions. Given information on infant clinical phenotypes in the FXpm and FXS is sparse, we aimed to characterize parent-reported infant temperament in infants with the FXpm (n=22) relative to FXS (n=24) and controls (n=24), assessed on 1-3 occasions each. Results suggested temperament in infants with the FXpm was largely typical, yet also resembled FXS in the negative affect domain, with trends toward suppressed negative affect in younger participants. In contrast, temperament features of infants with FXS consistently deviated from TD controls in both negative affect and surgency domains. These data suggest that FMR1 gene mutations are associated with atypical temperament that emerges as early as infancy, particularly among infants with FXS, warranting further study of whether temperament may index emergent clinical risks in these populations. Temperament, often referred to biologically-grounded emotional, attentional, and regulatory processes that guide individual responses to the environment (Rothbart & Derryberry, 1981), has been studied for decades as a salient and stable predictor of personality and psychopathology in typically developing populations. More recently, this work has begun rapidly expanding to subsets of the population with neurogenetic disorders as a means to inform the biological architecture contributing to these individual differences. The present study advances this work by providing an initial characterization of temperament in an understudied neurogenetic population at high-risk for psychopathology: infants with the