Neuropsychological Functioning in First-Degree Relatives of Individuals with Autism

Background: Unaffected first-degree relatives of individuals with autism show cognitive deficits that parallel impairments observed in probands with autism.  A comprehensive evaluation of neuropsychological domains in family members is needed to identify cognitive endophenotypes that reflect subtle neural system dysfunction that might be genetically determined. 

Objectives: To examine neuropsychological functioning across multiple domains in unaffected first-degree relatives of individuals with autism. 

Methods: Sixty-two first-degree relatives of individuals with autism and 31 age- and IQ-matched healthy control individuals between 8-55 years of age completed a neuropsychological battery spanning five domains: social functioning, communication, executive functioning, motor ability, and memory.  For the social-emotional domain, the Penn Emotion Differentiation Task and Social scale of the Autism Symptom Quotient (ASQ) were administered.  For the communication domain, the Peabody Picture Vocabulary Test – Third Edition (PPVT-III) and Communication scale of the ASQ were used.  Executive function measures included Spatial Span from the Wechsler Memory Scale-III (WMS-III), Trail-Making Test B, and Digit Span from the age appropriate Wechsler Intelligence Scale.  Motor tasks included the Grooved Pegboard Test and Finger Tapping Test.  Memory tests included both the Faces and Word Lists subtests from the WMS-III or Children’s Memory Scale (CMS).  Mean Z-scores were calculated across subtests within a given domain.  Individual tests also were examined.

Results: Family members showed worse performance than controls for the social-emotional and executive function domains, but no differences were observed for communication, motor, or memory domains.  Family members were slower to identify facial emotions, showed more social abnormalities on the ASQ, scored lower on Spatial Span and Digit Span, were slower to complete Trails B, and had greater difficulty shifting their attention as measured on the ASQ.  Family members also performed worse on the communication scale of the ASQ.  For family members, scores on the social, communication and attention switching scales of the ASQ were correlated.   Performance on the social scale also was associated with performance on Spatial Span, the latter of which was also significantly related to performance on Trails B.  For controls, only scores on social and communication scales of the ASQ were correlated.  Ratings on the social scale were correlated with Digit Span, and Trails B performance was associated with both Digit Span and Spatial Span.  Family members showed greater within-group variability on measures of executive functioning. 

Conclusions: First-degree relatives of individuals with autism show poorer performance on measures of social-emotional functioning, communication, and executive processing.  These lower performance patterns parallel the core features of autism.  Still, while reduced to a statistically significant degree, family members’ performance on all domains was in the average range and, for measures of executive functioning, was characterized by greater within group variability than is seen in controls.  In contrast, family members did not show performance deficits on tasks of motor, memory, or simple language functioning suggesting that a specific profile of neurocognitive performance characterizes relatives of individuals with autism better than a general intelligence factor.  This pattern may offer clues for selecting endophenotypes for family genetic research.