Nicotine Receptors May Play Role In Development of AutismCholinergic nicotinic receptors, which have become a hot area for brain researchers, are linked to yet another psychiatric-neurological disorder - autism.
Deep inside the human brain, cholinergic nicotinic receptors are busy plying their trade, and one might view them as triple agents. They release the nerve transmitter acetylcholine from certain nerve ends, they receive it at others, and they can be stimulated by nicotine - yes, from cigarette smoking!
Even more intriguing, these receptors have been implicated of late in a spate of psychiatric and neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, and Tourette syndrome (Psychiatric News, March 13, 2000).
And now the receptors have been linked to yet another psychiatric-neurological condition - autism.
The finding comes from Elaine Perry, Ph.D., of Newcastle General Hospital in Newcastle-Upon-Tyne, England, and her colleagues. It is reported in the July
American Journal of Psychiatry.
"This is an important paper," Peter Whitehouse, M.D., Ph.D., a neurologist-psychologist with Case Western Reserve University in Cleveland, told Psychiatric News. "It is probably the first [neurochemical] investigation of cholinergic systems in autism. And the findings regarding the nicotinic receptors do suggest a potential role for them in the mechanisms of autism, particularly related to the ability to focus attention and to interact with other people."
During the past few years, there have been intimations that the nerves and other brain mechanics that concern themselves with acetylcholine - the so-called "cholinergic systems" - might be implicated in autism. For example, cholinergic neurons in the basal forebrain, an area of the brain known to be involved in attention, have been found to be abnormally plentiful, and abnormally large, in children with autism.
As for a chemical known to influence the development and function of cholinergic neurons in the basal forebrain area - brain-derived neurotrophic factor - abnormally high levels of it have been found in the bloodstreams of newborns with autism. Thus, these and some other discoveries prompted Perry and her team to try to determine whether, and how, various cholinergic players conspire in the autism disease process.
They acquired frozen brain samples from seven deceased adults who had had autism and from 10 deceased adults who had no mental disorder. They then examined the activities of specific cholinergic functions in the brain samples and compared the activity of each function in brain samples from the autistic subjects with the activity in brain samples from the control subjects.
If any functions were found to behave abnormally in brain samples from autistic subjects, they reasoned, then those functions might well be culprits in the autism disease process.
For instance, the researchers measured in the brain samples the activity of acetylcholinesterase, the enzyme that makes acetylcholine. They then compared the activity of the enzyme in samples from the autism group with the activity of the enzyme in samples from the control group. They found no difference. So they concluded that this particular enzyme is probably not implicated in autism.
They also measured the activity of the enzyme that breaks down acetylcholine. They then compared the activity of this enzyme in samples from the autism group with the activity of this enzyme in samples from the control group. Again they found no difference. So they concluded that this enzyme, too, is not involved in autism.
However, they did find something interesting regarding the chemical that is known to influence the development and function of cholinergic neurons in the basal forebrain - that is, brain-derived neurotrophic factor.
They found three times more of the factor in the basal forebrain area of brain samples taken from autism subjects than in samples taken from mentally normal subjects. So they think that this factor might indeed be involved in autism.
And they also found considerably less nicotinic receptor activity in the cerebral cortex of brain samples taken from autism subjects than in the cerebral cortex of samples taken from mentally normal subjects. So they believe that faulty nicotinic receptors might also be culprits in autism.
Such findings, they concluded in their paper, suggest that "the role of the cholinergic system in autism should be investigated further. . . ."
Also of interest, they wrote, is that the abnormalities they have detected in brain samples from autism subjects more closely resemble those in brain samples from schizophrenia subjects than those in brain samples from Alzheimer's disease or Parkinson's disease subjects. Such similarities, they believe, are not surprising since "there is an extensive overlap in clinical symptoms between autism and schizophrenia, both behaviorally and cognitively. . .and the same neural systems are likely to be involved in both, although differing in developmental staging and etiology."
But the findings by Perry and her team
are especially provocative because they may point the way to an effective treatment for autism - something that does not currently exist. For instance,
might nicotine or another drug that stimulates the nicotinic receptors possibly help autism patients? Perry thinks so. In fact, she told
Psychiatric News, she would like to explore this possibility. The most recently approved drug for Alzheimer's disease - galantamine - might also be able to counter autism, Whitehouse conjectures. The reason, he said, is that the drug is thought to be capable of influencing the nicotinic receptors (
Psychiatric News, April 20).
The study, "
Cholinergic Activity in Autism: Abnormalities in the Cerebral Cortex and Basal Forebrain," is posted on the Web [
here] under the July issue.
Comment: It is interesting to note the extreme lengths to which this article goes to in its wording (and in the original headline, retained here as a subheading), to disguise the conclusion that nicotine can be beneficial. If one was to read the article too quicky, one could easily go away with the impression that Nicotine is being cited as a cause of autism, rather than a cure.