In another study, McDougle and colleagues published results of a clinical trial of Olanzapine treatment of children, adolescents, and adults with pervasive developmental disorders. Eight patients with autistic disorder or PDD were given olanzapine in an open-label, prospective fashion for 12 weeks.
Seven of eight patients completed the 12-week trial, and six of the completers were deemed clinical responders. Significant improvements in overall symptoms of autism, motor restlessness or hyperactivity, social relatedness, affectual reactions, sensory responses, language usage, self-injurious behavior, aggression, irritability or anger, anxiety, and depression were observed. Significant changes in repetitive behaviors were not observed for the group.
A daily dose of olanzapine was 7.8 +/- 4.7 mg/day was given. No evidence of extrapyramidal side effects or liver function abnormalities was seen. Preliminary results suggest that olanzapine may be an effective and well-tolerated drug in targeting core and related symptoms of PDDs in children, adolescents, and adults.
Dr. Michael Chez* published the results of a depakote (anticonvulsant) and steroid trial. This was an open-label trial on a small group of children with autism and PDD, many with EEG abnormalities. His paper suggests that this may be a useful intervention in a subset of children with autism.
His data show that a subset of children with autism (which may be as high as 50%) show abnormal EEG activity during sleep. In an earlier study, Dr. Isabel Rapin* has attempted to further distinguish a subset of children with autism who experience sudden and acute developmental and language regression and to relate this phenomena to epileptiform activity.
Additional Biochemical Studies Emerge
Brain metabolites in the hippocampus-amygdala region and cerebellum in autism were reported in an 1H-MR spectroscopy study by Dr. H. Otsuka and co-investigators working at the University of Tokushima, Japan. They examined 27 autistic patients and 10 normal children, using the STEAM sequence. The N-acetyl aspartate (NAA) concentration was significantly lower (P = 0.042) in autistic patients than in normal children.
In the further work of Chugani* from Wayne State University School of Medicine, Detroit, she has published data that show that in autistic children, N-acetyl-aspartate (NAA)levels are reduced compared to controls. Plasma lactate levels were higher in the 15 autistic children.
Sulphation deficit in "low-functioning" autistic children was the subject of a pilot study by Drs. Alberti and Waring. Alberti is located at the Oasi Institute for Research on Mental Retardation and Brain Aging in Troina, Italy. Waring is located in the U.K. The researchers investigated a group of 20 autistic children and age-matched controls. Utilizing the biochemical characteristics of paracetamol (tylenol) they evaluated by high-performance liquid chromatography, the urine paracetamol-sulfate/paracetamol-glucuronide ratio in all subjects following administration of this drug. The PS/PG ratio in the group of autistic subjects gave a significantly lower result than the control group.
Ted Page,* of the University of California, San Diego published two separate reports over the past two years describing different purine-related metabolic defects in subgroups of autistic patients. In the first paper, Page and his colleague Nyhan, report: "A syndrome of seizures and pervasive developmental disorder associated with excessive cellular nucleotidase activity." This syndrome presents with lack of language and social interaction, truncal ataxia and seizures.
It is treatable with oral administration of uridine. It is currently unknown what degree of overlap may exist between these patients and the autistic population. CAN has funded the development of a rapid-screening tool. Page and Colemen* report on purine metabolism abnormalities in a hyperuricosuric subclass of autism, in their recent paper describing a subclass of patients with classic infantile autism who have uric acid excretion, which is >2 standard deviations above the normal mean.
They state these hyperuricosuric autistic individuals may comprise approximately 20% of the autistic population. Their experiments show that de novo purine synthesis is increased approximately four-fold in the hyperuricosuric autistic patients. Although an enzyme defect responsible for the accelerated purine synthesis was not identified, the abnormal ratio of adenine to guanine nucleotides suggests a defect in purine nucleotide interconversion.
A recently released study by J. Zhang et al, describes results of analysis of compounds in the urine of autistic children with HPLC and mass spectrometry. This study was the joint effort of Repligen Corporation and University of Maryland School of Medicine, Baltimore.
Urine samples were collected from 40 autistic children aged 3-12 and 44 healthy children and analyzed by HPLC-MS/MS. The most significant difference in the two groups was a significant fraction (47%) of the autistic patients with undetectable levels of 7-methylxanthine in their urine. In a double-blind, placebo-controlled, crossover clinical study in 20 children the effect of placebo vs. secretin was evaluated on urinary metabolites.
There was a significant increase in urinary 7-methylxanthine following secretin, which was not observed following placebo administration. Four autistic children who had no detectable levels of 7-methylxanthine at the beginning of the study showed an increase of greater than 100-fold following secretin.
