The behavioural phenotype of autism was assessed in individuals with full mutation and premutation fragile X syndrome (FXS) using the Autism Diagnostic Observation Scale-Generic (ADOS-G) and the Autism Diagnostic Interview (ADI-R). The participants, aged 5-80 years, comprised 33 males and 31 females with full mutation, 7 males and 43 females with premutation, and 38 non-fragile X relatives (29 males, 9 females). In the full mutation group, a total of 67% males and 23% females met either the Autism Disorder (AD) or the Autism Spectrum Disorder (ASD) criteria on at least one of the diagnostic tests. In the premutation group, 14% males and 5% females met the ADOS-G criteria for ASD. The presence of autism manifestations in males and females with full mutation and premutation provide support for a spectrum view.

The current study investigated early temperament in 54 infants at familial high-risk of ASD and 50 controls. Parental report of temperament was assessed around 7, 14 and 24 months of age and diagnostic assessment was conducted at 3 years. The high-risk group showed reduced Surgency at 7 and 14 months and reduced Effortful Control at 14 and 24 months, compared to controls. High-risk infants later diagnosed with ASD were distinguished from controls by a temperament profile marked by increased Perceptual Sensitivity from the first year of life, and increased Negative Affect and reduced Cuddliness in the second year of life. Temperament may be an important construct for understanding the early infant development of ASD.

The distributions of scores for autistic behaviours obtained from the Autism Diagnostic Observation Scale-Generic (ADOS-G) were investigated in 147 males and females affected with the full mutation in the Fragile X mental retardation 1 (FMR1) gene, in 59 individuals with the premutation, and in 42 non-fragile X relatives, aged 4-70 years. The scores representing Communication and Social Interaction were continuously distributed across the two fragile X groups, and they were significantly elevated compared with the non-fragile X controls. Strong relationships were found between both these scores and FMRP deficits, but they became insignificant for Social Interaction, and the sum of Social Interaction and Communication scores, when FSIQ was included as another predictor of autism scores. Other significant predictors of these scores in both sexes were those executive skills which related to verbal fluency, and to the regulation and control of motor behaviour. Overall, our data have shown that cognitive impairment, especially of verbal skills, best explains the comorbidity of autism and fragile X. This implies some more fundamental perturbations of specific neural connections which are essential for both specific behaviours and cognition. We emphasize that FXS offers a unique molecular model for autism since FMRP regulates the translation of many other genes involved in synaptic formation and plasticity which should be natural targets for further exploration.

The behaviours of infants were observed using home videos, in an attempt to identify social difficulties characteristic of infants with autistic disorder. Three groups of infants were analysed: 15 infants who had later been diagnosed with autism, 15 infants who had a developmental or language delay, and 15 typically developing infants. Social behaviours were coded using both quantitative and qualitative measures. The principal discriminating items between the groups were found to be 'peer interest', 'gaze aversion', 'anticipatory postures', and 'proto-declarative showing'. The results suggest that these children later diagnosed with autism are clinically distinct from their peers before the age of two years, and that there are clearly observable behaviours which are important predictors of autistic disorder in pre-verbal children.

The aim in the current study was to investigate the early development of joint attention, eye contact and affect during the first 2 years of life, by using retrospective parental interviews and analyses of home videos of infants who were later diagnosed with Autistic Disorder (AD). The 36 children with AD and the 27 matched control children were all aged between 3 and 5 years at recruitment. Reported anomalies in gaze and affect emerged in the children with AD as early as the first 6 months of life, generally becoming more severe just prior to the second birthday. Video data confirmed these anomalies from as early as the first year. Joint attention impairments were found throughout the second year of life. The results suggest that early dyadic behaviours-eye contact and affect-may play a role in the joint attention impairment in AD.