Pat Palmer

An autosomal genomic screen for autism

Autism is a severe neurodevelopmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood. The etiology of idiopathic autism is strongly genetic, and oligogenic transmission is likely. The first stage of a two-stage genomic screen for autism was carried out by the Collaborative Linkage Study of Autism on individuals affected with autism from 75 families ascertained through an affected sib-pair. The strongest multipoint results were for regions on chromosomes 13 and 7. The highest maximum multipoint heterogeneity LOD (MMLS/het) score is 3.0 at D13S800 (approximately 55 cM from the telomere) under the recessive model, with an estimated 35% of families linked to this locus. The next highest peak is an MMLS/het score of 2.3 at 19 cM, between D13S217 and D13S1229. Our third highest MMLS/het score of 2.2 is on chromosome 7 and is consistent with the International Molecular Genetic Study of Autism Consortium report of a possible susceptibility locus somewhere within 7q31-33. These regions and others will be followed up in the second stage of our study by typing additional markers in both the original and a second set of identically ascertained autism families, which are currently being collected. By comparing results across a number of studies, we expect to be able to narrow our search for autism susceptibility genes to a small number of genomic regions.

Course of Behavioral Change in Autism: A Retrospective Study of High-IQ Adolescents and Adults

OBJECTIVE The course of behavioral change in autistic behaviors has received little attention in previous research but is a potentially important parameter for study in autism. METHOD Autistic behaviors were systematically examined in 38 high-IQ adolescent and adult autistic individuals at their current age (13 through 28 years) and retrospectively at age 5 years using a standardized interview for autism. RESULTS Significant change over time in autistic behaviors, generally in the direction of improvement, was detected. The proportion of subjects showing improvement in communication and social behaviors was found to be significantly higher than the proportion showing improvement in ritualistic/repetitive behaviors. Five of 38 subjects who met DSM-IV criteria for autistic disorder at age 5 years no longer met criteria at their current age, although all five continued to have substantial impairment. CONCLUSIONS The study of patterns of behavioral change over time in autism has practical implications for both diagnosis and prognosis as well as potential importance in defining biologically meaningful subgroups and clarifying fundamental mechanisms underlying this disorder.

Personality and Language Characteristics in Parents From Multiple-Incidence Autism Families

Several studies have suggested that the genetic liability for autism may be expressed in non-autistic relatives of autistic probands, in behavioral characteristics that are milder but qualitatively similar to the defining features of autism. We employ a variety of direct assessment approaches to examine both personality and language in parents ascertained through having two autistic children (multiple-incidence autism parents) and parents of Down syndrome probands. Multiple-incidence autism parents had higher rates of particular personality characteristics (rigidity, aloofness, hypersensitivity to criticism, and anxiousness), speech and pragmatic language deficits, and more limited friendships than parents in the comparison group. The implications of these findings for future genetic studies of autism are discussed.

The effect of co-morbidity and penetrance estimation on the outcome of linkage analysis in a bipolar family

In order to demonstrate the impact of co-morbidity and penetrance estimation on linkage analysis, a single bipolar family containing co-morbidity was examined for linkage to c-Harvey ras-1, and Glucose-6-phosphate dehydrogenase

Linkage of c-Harvey-ras-1 and INS DNA markers to unipolar depression and alcoholism is ruled out in 18 families

SummaryEighteen families informative for c-Harveyras-1 and INS DNA markers were tested for linkage to unipolar depression and alcoholism. No evidence of linkage was found between these DNA markers and the disorders observed in the families. This study fails to replicate the Old Order Amish Study and suggests that a significant degree of genetic heterogeneity may be present among psychiatric disorders.

Cognitive deficits in parents from multiple-incidence autism families

This study compares parents of two autistic children with parents of a Down syndrome (DS) proband, on tests of intelligence, reading and spelling, and executive function. Autism parents performed significantly worse than DS parents on performance IQ, a test of executive function, and some reading measures (e.g. passage comprehension and rapid automatized naming). These results suggest that cognitive deficits may be an expression of the underlying genetic liability for autism and that these characteristics may contribute to a more broadly defined autism phenotype.