Outcome classification of preschool children with autism spectrum disorders using MRI brain measures.

Objective: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome.

Method: Quantitative MRI technology was used to measure gray and white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.

Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species.

Transmission disequilibrium studies of the serotonin 5-HT2A receptor gene (HTR2A) in autism.

Hyperserotonemia in autism is one of the longest-standing biochemical findings in a psychiatric disorder. This well-replicated finding and subsequent studies of platelet serotonin receptors in autism indicate that the serotonin 2A receptor gene (HTR2A) on chromosome 13q is a primary candidate gene in autism. Converging data from recent genome screens also implicates the genomic region containing HTR2A.

Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder.

The serotonin transporter gene (SLC6A4, MIM 182138) is a candidate gene in autistic disorder based on neurochemical, neuroendocrine studies and the efficacy of potent serotonin transporter inhibitors in reducing ritualistic behaviors and related aggression. An insertion/deletion polymorphism (5-HTTLPR) in the promoter region and a variable number of tandem repeat polymorphism (VNTR) in the second intron, were previously identified and suggested to modulate transcription. Six previous family-based association studies of SLC6A4 in autistic disorder have been conducted, with four studies showing nominally significant transmission disequilibrium and two studies with no evidence of nominally significant transmission disequilibrium.

Mutation screening and transmission disequilibrium study of ATP10C in autism.

Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11-q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies.

Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study.

Objective: To quantify developmental abnormalities in cerebral and cerebellar volume in autism.

Methods: The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older.

Physical mapping of the serotonin 5-HT(7) receptor gene (HTR7) to chromosome 10 and pseudogene (HTR7P) to chromosome 12, and testing of linkage disequilibrium between HTR7 and autistic disorder.

The gene encoding the serotonin 5-HT(7) receptor (HTR7) has been considered as a candidate locus in several neuropsychiatric disorders, based on pharmacological evidence and ligand-binding studies. After determining over 3 kb of previously unpublished sequence from introns 1 and 2 of HTR7, a single base (C/T) polymorphism in the second intron of HTR7 was found. Allele-specific PCR was used to genotype the HTR7 marker in 53 trios consisting of subjects with autistic disorder and both parents.

Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.

Autistic disorder is a complex genetic disease. Because of previous reports of individuals with autistic disorder with duplications of the Prader-Willi/Angelman syndrome critical region, we screened several markers across the 15q11-13 region, for linkage disequilibrium. One hundred forty families, consisting predominantly of a child with autistic disorder and both parents, were studied.

Evidence of linkage between the serotonin transporter and autistic disorder.

The serotonin transporter gene (HTT) is a primary candidate in autistic disorder based on efficacy of potent serotonin transporter inhibitors in reducing rituals and routines. We initiated a candidate gene study of HTT in trios consisting of probands with autistic disorder and both parents. Preliminary transmission/disequilibrium test (TDT) analysis with 86 families revealed no evidence for linkage or linkage disequilibrium between autistic disorder and a polymorphism in the second intron of HTT.

Autism or atypical autism in maternally but not paternally derived proximal 15q duplication.

Duplications of proximal 15q have been found in individuals with autistic disorder (AD) and varying degrees of mental retardation. Often these abnormalities take the form of a supernumerary inverted duplicated chromosome 15, more properly described as an isodicentric chromosome 15, or idic(15). However, intrachromosomal duplications also have been reported.

Functioning of the brain-stem auditory pathway in non-retarded autistic individuals.

Functioning of auditory brain-stem pathways was examined in non-retarded autistic individuals (14-28 years of age). Functioning was assessed by recording ERPs (event-related brain potentials) generated by these auditory pathways. These ERPs were evoked by click stimuli and occurred within the first 8 msec following the onset of the click.