Neurobiological Perspectives on Autism

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Biology 202
1999 Final Web Reports
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Neurobiological Perspectives on Autism

Lauren Hellew

Autism is a pervasive developmental disorder characterized by restricted, repetitive, and stereotyped patterns of behavior, along with severe impairments in reciprocal social interaction, verbal and non-verbal communication, and cognitive development (1,2,3). If the brain is responsible for behavior then it should follow that disordered autistic behaviors should be explainable in terms of brain abnormalities and disordered neurobiological processes. While findings are generally speculative and the etiology of the disorder remains somewhat of an enigma, there is significant evidence that autism is associated with neurobiological dysfunction.

Autistic individuals are often highly socially withdrawn to the extent that they may appear to live in a world of their own. Infants typically fail to develop normal attachments to parents or caregivers. They may seem indifferent to other's gestures of affection towards them, and may even resist being held or otherwise engaged in physical or emotional interaction. They tend to make little or no use of eye contact, smiling, facial expressions, gestures, and other signals of social intent. They continue to manifest many of the same social impairments throughout childhood, adolescence, and adulthood. For example, they typically fail to develop normal peer relationships and they generally demonstrate an impairment in social-emotional reciprocity. Normal displays of emotion or empathy are uncommon: they do not generally offer comfort to others, nor do they seek others for comfort in their own times of distress. Similarly, they lack the ability to share in the enjoyment of other's pleasure and they resist sharing their own enjoyment with others.

Restricted, repetitive, and stereotypical patterns of behavior and interest are also typical in autism. Autistic individuals often demonstrate repetitive motor mannerisms, including body rocking and hand/finger flapping or twisting. They can demonstrate apparent compulsive adherence to certain routines, and may become highly distressed upon changes to such rituals. They may become preoccupied with unusual objects, and/or very specific (and often bizarre) interests. In higher functioning individuals, such insistence on sameness may be manifested as a narrow range of interests, whereas, in lower functioning individuals, it may result in a preoccupation with, and attachment to, an unusual object or parts of objects.

Individuals with autism generally demonstrate delayed or deviant verbal and non-verbal communication. In fact, poor communication skills are found in nearly all autistic children, and some autistic individuals never acquire functional speech. Those who do acquire speech often have pragmatic difficulties with the language, and are generally unable to use it in a socially communicative fashion. They may display abnormalities in the volume, stress, rate, rhythm, and intonation of their speech. Bizarre uses of language are also common. For example, ecolalia (repeating heard words or phrases), and palelalia (repeating oneself), are often seen in autism. In addition, disturbances in responses to sensory stimuli (particularly hypersensitive hearing or hyperacusis) are also common in autism.

There is evidence that autism is associated with specific structural brain abnormalities. Relatively recent research in this area has been conducted by Dr. Eric Courchesne, in conjunction with the San Diego Children's Hospital and the University of California in San Diego (4,5,6). Using magnetic resonance imaging (MRI) to contrast the brains of normal subjects with those of individuals with autism, Courchesne has found that certain areas of the cerebellum are distinctly underdeveloped in autistics. The cerebellum is a relatively large portion of the brain located near the brain stem that is primarily responsible for motor movements, but may also play a role in speech, learning, emotions, and attention. Thus, cerebellar abnormalities may help to explain the aberrant motor activity, impaired cognitive abilities, and apparent lack of emotion that are characteristic of autism.

In particular, results of comparative brain imaging studies have shown that two areas of the cerebellum, vermal lobules VI and VII, are significantly smaller in autistic individuals. These regions of the cerebellum are connected to brain regions that specifically govern attention, arousal, and the assimilation of sensory stimulation. Based on such results, Courchesne has developed a "Theory of Overstimulation" that emphasizes the idea that autistic individuals are chronically overstimulation by confusing and inconsistent activity of their disordered brains. He suggests that individuals with autism are abnormally subject to stimulation because of specific brain deficiencies and that, as a result, they try to shield themselves from additional stimuli. Courchesne takes the theory one step further to suggest that there is a brain mechanism through which repetitive and rhythmical behavior can have a calming effect on the cerebral cortex. Thus, certain characteristic features of autism, including sensitivity to sensory stimuli and repetitive behavior, may be explained in terms of structural abnormalities in the cerebellum.

There is also evidence that autistic individuals have dramatically reduced levels of Purkinje cells in the cerebellum. These cells, which are rich in the neurotransmitter serotonin, transmit inhibiting messages from the cerebellum to areas of the cerebral cortex. Given that the cerebral cortex is thought to be the center of thinking and judging, the dearth of communication with this area may help to explain some of the cognitive deficits characteristic of autism.

Evidence has also suggested that autism may be related to specific neurological damage to the limbic system (4,7). A great deal of research in this area has been conducted by Drs. Bauman and Kemper of Harvard Medical School and Boston University School of Medicine, respectively. These researchers have examined post-mortum brains of autistic individuals and have found the amygdala and the hippocampus to be underdeveloped. In particular, they have reported finding densely packed, unusually small neurons in the amygdala and hippocampus of autistic individuals. While the exact implications of these findings remain somewhat speculative, examination of the normal functions of these structures as well as related animal research may help to explain how such neurological damage may be connected to the traits and behaviors associated with autism.

The amygdala is thought to play a role in the control of aggression and emotion. This is significant in that autistics are often either overly aggressive or passive and may appear emotionless. When the amygdala is damaged or removed, animals exhibit social withdrawal, compulsive behaviors, failure to learn about dangerous situations, memory deficits, and difficulty adjusting to novel situations - characteristics that are similar to those seen in autism. The amygdala may also function in response to various types of sensory stimuli, another system which appears to function abnormally in autistics (7). The hippocampus is thought to be primarily responsible for learning and memory. It has been hypothesized by Dr. Bernard Rimland that autistic individuals have a specific cognitive deficit related to learning and memory. When the hippocampus is damaged or removed, animals demonstrate an inability to store new information into memory and they often display characteristics commonly seen in autism, including stereotypic, self-stimulatory behaviors, and hyperactivity (7).

Additional brain abnormalities that may be associated with autism have been found via imaging studies of the brains of people suffering from tuberous sclerosis (TS) (8). TS patients are known to have a much higher risk of developing autism than the general public. A comparison of TS patients with autism and those without autism has shown that those with autism are more likely to have tube-like growths of enlarged brain cells on the temporal lobes of their brains than are TS patients without autism. Such data suggests that some TS suffers develop these abnormal growths and that these growths may be linked to autism.

A recent brain imaging study involving identical twins, one of which was autistic and the other of which was not, has further examined the structural brain abnormalities associated with autism (9). This study, which was conducted by Wendy Kates and her colleagues at Johns Hopkins University, the Kennedy Kreiger Institute, and Stanford University, found that the autistic twin had a smaller amygdala and a smaller hippocampus relative to his normal brother. In addition, parts of the cerebellum that are involved in shifting attention were found to be smaller in the autistic twin than the non-autistic twin. Furthermore, both twins had a reduced frontal cortex, an area responsible for executive functions including organizing, planning, and problem solving, and a reduced superior temporal gyrus, a region responsible for processing language. Interestingly, the non-autistic twin did show some autistic-like behavioral and communication problems. Such evidence implicates the above brain regions in the etiology of autism and suggests that there may be a mild form of autism that may affect relatives of autistic individuals.

Several findings have implicated neurochemical dysfunctions in individuals with autism. Additionally, there is some evidence that therapeutic medications which act directly on these neurochemical systems (including fenfluramine, haloperidol, risperidone, clonidine, and naltrexone) can effectively decrease the aggressive, obsessive-compulsive, and self-stimulating behaviors associated with autism in controlled drug trials.

Autism has been associated with abnormalities of the brain domaminergic system (10,11). Specifically, it is thought that autistic individuals have increased levels of brain dopamine. This is demonstrated by the fact that intellectually subnormal autistic children with severe hyperactivity and stereotypes have been shown to have high cerebrospinal fluid levels of levels of the dopamine metabolite homovanillic acid. Furthermore, the use of dopamine antagonists such as haloperidol has been shown to have modest success in decreasing hyperactivity, negativism, and stereotyped behaviors, and facilitating learning in autistics. The dopaminergic system is known to affect motor behavior. Abnormalities of this system are associated with excess motor activity and stereotyped behaviors, traits often observed in autistic patients.

It has also been hypothesized that autism is related to a dysfunctional serotonergic system, and that such dysfunction may be responsible for the sensory and perceptual abnormalities seen in these patients (4,10,11). Evidence for this theory comes in part from studies that have shown increased platelet serotonin concentrations in autistic individuals. Additionally, studies of fenfluramine, a medication that reduces brain serotonin, have shown that the drug may be beneficial in treating some cases of autism.

There is also evidence that some autistic individuals have elevated levels of beta-endorphins, an endogenous opiate-like substance in the body (4,10,11). It has been shown that neonatal rats and chicks exposed to high levels of opiates show autistic-like symptoms after they are born. In particular, they exhibit unusual motor flurries similar to the hyperactivity seen in autistic children and they fail to show normal separation anxiety when removed from their mothers. In addition, opiate addicts often demonstrate social withdrawal, self-stimulation, and high levels of pain tolerance - symptoms often associated with autism. While such evidence suggests that opiate antagonists such as naltrexone may be beneficial in treating autism, such a treatment has not proven to be very effective.

Abnormalities of the noradrenergic system have also been associated with autism (4,10,11). In particular, norepinephrine agonists have been shown to worsen the behaviors of autistic patients, and increases in norepinephrine plasma concentrations have been reported in autistics. However, treatment of autism with norepinephrine antagonists such as clonidine has not proven to be very effective.

A great deal of attention has recently been focused on the polypeptide hormone secretin as a possible treatment for autism (12,13,14). Secretin is a hormone messenger secreted by "S" cells in the duodenum during digestion. The function of secretin is to increase the production and secretion of alkaline digestive fluids by the pancreas, thus facilitating the neutralization of partially digested food that has been acidified by hydrochloric acid in the stomach. Initial use of secretin as a treatment for autism was based on a report of three autistic children who were subjected to a test of pancreatic function that involved the intravenous administration of secretin, and who subsequently demonstrated significant behavioral improvements including increased eye contact and expressed language. Since that report, approximately 2,500-3,000 autistic children have been treated with secretin with generally positive results. While the mechanism through which secretin exerts its therapeutic effects is unclear, it is hypothesized that the hormone may affect the brain. There is some preliminary evidence from animal studies to suggest that there are secretin receptors in the brain. Despite the questionable nature of the mechanism responsible for the apparent effectiveness of secretin, the fact that such a neurobiological intervention can have a potentially dramatic effect on behavior suggests that the behavior is directly mediated by neurobiological processes.

Thus, it seems that there are several structural and neurochemical abnormalities associated with autism that can help to explain the specific behaviors and deficits characteristic of the disorder. This demonstrated link between brain and behavior is significant on several levels. In terms of the etiology of the specific disorder, localization of physiological dysfunction suggests biological, rather than psychological, social or otherwise non-biological causality. Given that only a few decades autism was commonly thought to result from unaffectionate "refrigerator" mothers, this move towards biologically based explanations is certainly significant. On a more general level, the neurobiological basis of autism is suggestive of a more general brain-behavior connection.

WWW Sources

1)Autism Research Institute

2)Center for the Study of Autism

3)Autism Society of America

4)AUTISM: Overview of Autism

5)The Cerebellum and Autism

6)Autism and the Brain

7)Autism and the Limbic System

8)Brain Lesions Linked to Autism

9)Researchers Identify Brain Abnormalities in Autistic Children

10)Pediatric Psychopharmacology: Autism

11)Progress in the Neurobiology of Autism

12)Secretin: A Treatment for Autism? (Autism Biomedical Information Network)

13)Secretin Information (Autism Research Institute)

14)The Use of Secretin to Treat Autism (National Institute of Child Health and Human Development)

 

 

Continuing conversation
(to contribute your own observations/thoughts, post a comment below)

01/19/2006, from a Reader on the Web

To whom it may concern: My name is Erin and I am a Special Education major at Towson University. I just read the article "Neurobiological Perspectives on Autism" and while I thought the article was informative and overall well written, I do have one suggestion. When you are writing or speaking about individuals with disabilities, it is more appropriate and respectful to use people first language. People first language simply means that you identify the person before the disability, since a person is not defined by their handicaps. For example, rather than saying "autistic individuals" or "autistics," say "individuals with autism" or "individuals who are autistic." The author of the article varied her use of people first language with non-people first language. Overall, the use of people first language extends the respect for the disability and its research to the individuals and their families who are living with the disability. Thanks.

 

Comments

Serendip Visitor's picture

Too much dopamine but what of slightly less than enough?

Some autistics have too much serotonin, but others too little. Could small dopamine adjustment help?

Serendip Visitor-tony's picture

Comments

I have a wonderful three year old boy who happens to be autistic...this was a great article. As a general rule I like to have an informed opinion, especially when it comes to my sons disability...at this point this is where I'm at: I've met a good number of kiddos on the spectrum, no two are the same...and much like they are not the same, I'm also aware that for some simple speech therapy worked the trick, for some ABA is the thing that works, heck, there's a number of schools running under the DIR/floortime where I live...whatever works for your kid, do it! Nothing is guaranteed...that's for sure! As to the causes...I have heard so many things, it's just baffling...from vaccines, gut leakage, immunodeficiency...you name it! As a parent I try to stay informed and make the best decisions I can, I have to admit considering outlandish solutions like the hyperbaric chamber, but never the mms protocol...now I can't really pass judgement on those who do...everyone has to gather the best data and pray it works for their kid. It's easy to criticize others decisions, not me I can't fall in that trap...I'd rather stay focused on helping my son

lisagibsonSerendip Visitor's picture

understanding him to help him communicate to educators ect.

. . . . My son is six. He doesn't express pain very well. Usually he cries when he's overstimulated at school. Which is everyday. He is highly functional, yet he has alot of anxiety, due to over stimulation in which the school has to many children to worry about accommodation for one child. I say things the wrong way usually out of anger or frustration, because I know my son. I want to help him, so he can communicate to educators and more to us. I've learned that he gets in trouble in situations because he cannot express what has happened. Children take advantage of him and he gets blamed for things, he hasn't done. Unless you ask him directly what happened, in general he doesn't lie even if he's done wrong. He's been on risperdone for approx. 3 months and he usually tells me his most dramatic thing that happened in school when i pick him up, however later in time he tells me things that have happened and i have confirmed them. Before the medicine we only new what his teachers told us or what I've seen myself. Any ideas on helping him cope in school due to over stimulation? And not being able to tell them or us why he's crying. Can u recover from autism?

Josh's picture

Question

How old are the tested subjects with autism? Could it be possible that some of the brain and functional changes that appear in a study are due to the lack of use of these muscles in the brain? For example, is it possible that a newborn that has undiagnosed autism has all the normal sized parts mentioned in this article, and they progressively shrink through inactivity?

Renee Anne's picture

Person First Language and Vaccines

I, also, am a student working toward my special education degree, and currently have a degree in elementary education and psychology.

I would like to say that although professors and instructors force-feed person first language down our throats, it is NOT always acceptable. There is a movement among autistic people to be called just that: Autistic People. Not "someone that has autism" or "someone who suffers from a disorder on the autism spectrum." Yes, they are people first...but their autism defines them.

The best thing to do: ASK! No, seriously, ask them what they want to be called.

As for vaccines in children: I do understand the research on vaccination of children and it's supposed link to autism. Do I agree that there could be a connection between the two? Yes, there very well could be a connection between vaccination of children and autism. HOWEVER, because the diseases that vaccinations take care of have not been eradicated (no matter what the media likes to tell us - go to a third world country and then come back and tell me polio has disappeared), I would prefer an autistic child to a dead one. I know it sounds harsh but vaccinations are helpful in warding off deadly diseases.

Serendip Visitor's picture

Sorry.. I really don't care

Sorry.. I really don't care where you study. Autism does not define my son. Does lack of intellect define yours?

Serendip Visitor's picture

autism and vaccines - no alternative?

Consider looking into homeopathic nosodes instead of conventional vaccination -- aside from the difference in the active agent(s) in one versus the other, there is the homeopathic principle (which is evident in many therapies) of "less is more"; in other words, if you evoke a reaction rather than imposing a stimulus on the body, you may get a more effective and powerful response instead of the body/brain/etc. shutting down and blocking out.

We have personally seen this difference in several very different therapies with our autistic son, including HBOT vs LBOT, EM-based stimulation, sensory integration vs. sensori-motor therapy, AIT when over-modulated, etc.

If you think about it, over-stimulus with any therapy in dealing with autism is bound to have unhelpful rebound effects. Just think about it. And we're not even talking about unfriendlies like mercury, necessarily -- but we should be thinking about both that and, in the absence of that, just FOREIGN PROTEINS WITHOUT THE INTERVENTION OF THE GUT/PANCREAS, ETC.

And now the final coup de gras: isn't the government now allowing the addition of the rejected thimerosal into all the flu vaccines it's pushing on the public (without informing us of that fact) -- as well as their recent history (what, 20 years or more now?) of ganging up more and more vaccines on our children earlier and earlier?

Autism isn't death but it isn't life as it was meant to be, either. Once in awhile we get to see a brief glimpse of the unpained person our son was meant to be, and it is a heady picture and we keep looking for things to keep him more and more on "this side of life."

Think about what external things may have contributed to your child's autism to begin with; it's a good bet they amount to a forceful imposition from some agent or other. In our own case, I'm quite persuaded that Pitocin/anesthesia/aggressive L&D techniques played a major part. There is a June 1991 four-hospital Japanese study that supports what I concluded back in 1981 when our son was only 4 years old.

Do consider nosodes vs. vaccination, gentle vs. aggressive, evoking response instead of overwhelming the body and its natural defenses.

Anonymous's picture

Outgunned by Pretty Actress

Too bad this scientific research will not change the minds of the millions of Americans who see Jenny McCarthy on CNN and believe that the accelerated vaccine schedule and food allergies are the primary causes of autism. (Try not to let the fingers-in-the air quotes when they say the word "science" bother you too much either.)

Serendip Visitor's picture

I gotta ask -- I'm new to

I gotta ask -- I'm new to this site -- you know the old saying, "Ask the man who owns one"?

Do you?

A lot of parents have spent literally years worth of time researching their child's issues in any number of ways and have put out lots of money running through therapies and finding out which works and which doesn't for their child, and they actually even learn clues as to what areas of their children's brains might be involved, etc. On top of that, they have an intimate bird's eye view of their own child's history, like: "gee, his left left was straight when he was born, now at six weeks it curves inward" -- and, later, "gee, his left testicle still isn't descended"... -- and then you learn he has "white noise" in his left ear for as long as he can remember -- as well as a bunch of autistic symptoms -- and you think, "gee, it couldn't be vaccines because he was symptomatic before his first one (at 18 months," in our case, back in 1979) -- and then you find out that the FDA doesn't recommend using Pitocin in labor since 1978 when he was a year old and the good puppy breeders have quit using it...etc...

You know? "Ask the man who owns one." There's science and there's common sense. Sometimes they actually intersect and sometimes it's just us dumb breeder parents who see the connection.

Diane's picture

Autism and overstimulation

My grandson is recovering from Autism and we have pinpointed the timeframe when the symptoms began to develop. Right after his MMR shot so unless you have dealt with Autism please refrain from judgment. The pretty Actress saved my grandson's life. Because of her courage my grandson was immediately into treatment and is progressing.

He has no problem with memorization. He learns by memorizing. He is 3 1/2 and can read and write the alphabet both frontwards and backwards. He can write his name. Through his biomedical treatment he has become loving and affectionate.
I agree that there are some genetic predispositions that are accelerated by the toxins in vaccines. These children have something wrong with their immune systems when they are born and the use of vaccines create conditions that their immune systems cannot handle and they become overloaded.

Serendip Visitor's picture

There is almost no

There is almost no statistical proof to suggest that the vaccine thory is correct. I too have a form of autism, albeit a very minor form,a lthough in the newest dsm they lumped us all together. Part of the reason why children begin to develop the neurological charachteristics of autism around the age of there first vaccination is due to the fact that this age is associated with a large amount of synaptic pruning which is a mechanism the brain uses to decide which denritic connections to other neurons are usefull and which are not. it is theorized that in those of us with autism this process does not properly occur. There is still research on that topic to be done but i will say that the vaccine idea has very little merit because hte effects of autism do not match the effects of neurotoxicity that would normally be associated with the heavy metals that are supposedly the cause of autism according to this theory. Furthermore the idea that the immune system is implicated is rather erroneous because most doctors beleive gastric difficulties some autistic people experience are comorbid conditions as a statistically significant percentage of autistic individuals including myself have no gastrointestinal problems and a properly functioning immune system. Autism is definitely something that defines somones life, i can socialize and i have friends but i dont have the social life of a neurotypical individual and i never will but i have an incredibly high iq, and i can tell you that while autism may impact the quality of life that some people experience, there are ways to improve your quality of life by not focusing on your disibality and on what you can do.

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