Nicotine Receptors May Play Role In Development of Autism
Cholinergic nicotinic receptors, which have become a hot area for brain
researchers, are linked to yet another psychiatric-neurological
By Joan Arehart-Treichel in Psychiatric News, July © 2001 American
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
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
in the July American Journal of Psychiatry.
“This is an important paper,” Peter Whitehouse, M.D., Ph.D., a
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
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
The study, “Cholinergic Activity in Autism: Abnormalities in the
Cerebral Cortex and Basal Forebrain,” is posted on the Web at
http://ajp.psychiatryonline.org under the July issue.