Neurobehavioral abnormalities in first-degree relatives of individuals with autism.
BACKGROUND
Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder.


OBJECTIVE
To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism.


METHODS
Case-control comparison of neurobehavioral functions.


METHODS
University medical center.


METHODS
Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years).


METHODS
Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors.


RESULTS
On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another.


CONCLUSIONS
Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism.
Mosconi
Matthew W
MW
Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Kay
Margaret
M
D'Cruz
Anna-Maria
AM
Guter
Stephen
S
Kapur
Kush
K
Macmillan
Carol
C
Stanford
Lisa D
LD
Sweeney
John A
JA
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D056344:Executive Function / Q000502:physiology; D005133:Eye Movements / Q000235:genetics / Q000502:physiology; D005190:Family / Q000523:psychology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D011698:Pursuit, Smooth / Q000235:genetics / Q000502:physiology; D012438:Saccades / Q000235:genetics / Q000502:physiology