Final Activity Report Summary - ASTER (Neurobiology of autism: the role of steroids and mercury)
This research-educational project had two goals: 1) to test in clinical and preclinical studies the potential links between autism, exposure to mercury, and steroid hormones; and 2) to supervise doctoral students in their biomedical research. Both goals have been achieved. The clinical study compared the cohorts of 91 autistic children and 75 healthy children, 3-4 and 7-9 years old, with respect to the neonatal clinical measures, development, vaccination history and complications, mercury content in hair, and the levels of steroid hormones in saliva.
The study was conducted at the Institute of Psychiatry and Neurology in Warsaw. The autistic children were diagnosed by experienced specialists. The medical histories of the autistic and control children were taken from the parents and from Child Health Notebooks about pregnancy, labour, mental and motor development of the child, illnesses and traumatic events, vaccinations, the occurrence of vaccine-associated adverse effects, and the occurrence of first symptoms of autism. The control children were recruited from preschools and elementary schools. The results show that in demographic and perinatal measures there were no consistent statistically significant differences between the autistic and control cohorts. The autistic children had a greater prevalence of adverse reactions after vaccinations and more abnormal development than the healthy controls. Between 45 and 80% of the autistic children experienced developmental regress. The autistic children significantly differed from the healthy children in the levels of hair mercury: the younger autistics had lower levels, while the older had higher levels than those of the controls. The environmental exposure to mercury (including that from vaccinations) between the autistic and healthy children did not appear to be different. The results suggest that autistic children may have impaired elimination of mercury from their bodies, thus may be more vulnerable to its toxic effects. The analysis of saliva samples showed increased levels of androgens in autistic children, as compared to those of the healthy controls.
The aim of preclinical studies was to test in an animal model the developmental neurotoxicity of thimerosal (Thim), an organomercury vaccine preservative suspected in autism pathogenesis, and to test the involvement of steroid hormones in this process. Behavioral, neuropathological and neurochemical techniques were used. Thim at doses (12 - 3000 microgr Hg/kg) was injected intramuscularly to rat pups in a vaccination-like mode on postnatal days 7, 9, 11 and 14. The lowest Thim dose is equivalent to doses used in child vaccines. The rats' development and behaviour was monitored. The results showed an accumulation of Thim-Hg in the brain and other organs, which persisted longer than 30 days after the injection. The Thim injection caused persistent behavioural changes in rats: impaired locomotor activity, enhanced anxiety, altered social interactions, deficient sensitivity to pain, altered sensitivity to morphine and neuroleptics, with minimal impairments of spatial memory. Some of these changes were seen at the lowest Thim dose. The neuropathological tests showed wide-spread abnormalities in neurons and glia in several brain regions, such as ischemic changes in neurons of the prefrontal and temporal cortex, hippocampus, cerebellum and amygdala, changes in the astroglia and blood vessels, loss of synapses, reduced densities of dopamine receptors in the striatum, increased densities of opiate receptors in regions linked to pain perception, but decreased densities in the hippocampus. A biochemical test showed that Thim injection increases extracellular levels of excitatory amino acids in the brain. Certain neurosteroids modulated these phenomena. Many of the observed Thim-induced effects resemble the abnormalities found in autistic patients. The Chair delivered 20 lectures and trained 4 Ph.D. students.
The study was conducted at the Institute of Psychiatry and Neurology in Warsaw. The autistic children were diagnosed by experienced specialists. The medical histories of the autistic and control children were taken from the parents and from Child Health Notebooks about pregnancy, labour, mental and motor development of the child, illnesses and traumatic events, vaccinations, the occurrence of vaccine-associated adverse effects, and the occurrence of first symptoms of autism. The control children were recruited from preschools and elementary schools. The results show that in demographic and perinatal measures there were no consistent statistically significant differences between the autistic and control cohorts. The autistic children had a greater prevalence of adverse reactions after vaccinations and more abnormal development than the healthy controls. Between 45 and 80% of the autistic children experienced developmental regress. The autistic children significantly differed from the healthy children in the levels of hair mercury: the younger autistics had lower levels, while the older had higher levels than those of the controls. The environmental exposure to mercury (including that from vaccinations) between the autistic and healthy children did not appear to be different. The results suggest that autistic children may have impaired elimination of mercury from their bodies, thus may be more vulnerable to its toxic effects. The analysis of saliva samples showed increased levels of androgens in autistic children, as compared to those of the healthy controls.
The aim of preclinical studies was to test in an animal model the developmental neurotoxicity of thimerosal (Thim), an organomercury vaccine preservative suspected in autism pathogenesis, and to test the involvement of steroid hormones in this process. Behavioral, neuropathological and neurochemical techniques were used. Thim at doses (12 - 3000 microgr Hg/kg) was injected intramuscularly to rat pups in a vaccination-like mode on postnatal days 7, 9, 11 and 14. The lowest Thim dose is equivalent to doses used in child vaccines. The rats' development and behaviour was monitored. The results showed an accumulation of Thim-Hg in the brain and other organs, which persisted longer than 30 days after the injection. The Thim injection caused persistent behavioural changes in rats: impaired locomotor activity, enhanced anxiety, altered social interactions, deficient sensitivity to pain, altered sensitivity to morphine and neuroleptics, with minimal impairments of spatial memory. Some of these changes were seen at the lowest Thim dose. The neuropathological tests showed wide-spread abnormalities in neurons and glia in several brain regions, such as ischemic changes in neurons of the prefrontal and temporal cortex, hippocampus, cerebellum and amygdala, changes in the astroglia and blood vessels, loss of synapses, reduced densities of dopamine receptors in the striatum, increased densities of opiate receptors in regions linked to pain perception, but decreased densities in the hippocampus. A biochemical test showed that Thim injection increases extracellular levels of excitatory amino acids in the brain. Certain neurosteroids modulated these phenomena. Many of the observed Thim-induced effects resemble the abnormalities found in autistic patients. The Chair delivered 20 lectures and trained 4 Ph.D. students.