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Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. “The LC-NA system is the only brain system involved both in producing fever and controlling behavior,” says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process sensory information.

It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another).

“What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks,” says Dr. Mehler.

Drs. Purpura and Mehler hypothesize that in autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors (chemical substances both within as well as outside the genome that regulate the expression of genes). They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.

Drs. Purpura and Mehler believe that, in autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function.

the future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.

“You can’t take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that’s folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way.”

"Although these are early days, we think this difference in stress hormone levels could be really significant in explaining why children with AS are less able to react and cope with unexpected change,"

If these Asperger symptoms are caused primarily by stress, caregivers could learn to steer children away from situations that would add to anxiety, the researchers said.

"This study suggests that children with AS may not adjust normally to the challenge of a new environment on waking,"

The researchers, whose findings were published in the journal Psychoneuroendocrinology, will next study if this lack of cortisol upon waking also occurs in children with other types of autism.

This study documented that autistic children experience behavior changes during fever.

Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. "The LC-NA system is the only brain system involved both in producing fever and controlling behavior," says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.

The locus coeruleus has widespread connections to brain regions that process sensory information. It secretes most of the brain's noradrenaline, a neurotransmitter that plays a key role in arousal mechanisms, such as the "fight or flight" response. It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another). Poor attentional focusing is a defining characteristic of autism.

"What is unique about the locus coeruleus is that it activates almost all higher-order brain centers that are involved in complex cognitive tasks," says Dr. Mehler.

autism, the LC-NA system is dysregulated by the interplay of environment, genetic, and epigenetic factors

They believe that stress plays a central role in dysregulation of the LC-NA system, especially in the latter stages of prenatal development when the fetal brain is particularly vulnerable.

a higher incidence of autism among children whose mothers had been exposed to hurricanes and tropical storms during pregnancy.

autistic children, fever stimulates the LC-NA system, temporarily restoring its normal regulatory function. "This could not happen if autism was caused by a lesion or some structural abnormality of the brain," says Dr. Purpura.

future of autism treatment probably lies in drugs that selectively target certain types of noradrenergic brain receptors or, more likely, in epigenetic therapies targeting genes of the LC-NA system.

If the locus coeruleus is impaired in autism, it is probably because tens or hundreds, maybe even thousands, of genes are dysregulated in subtle and complex ways," says Dr. Mehler. "The only way you can reverse this process is with epigenetic therapies, which, we are beginning to learn, have the ability to coordinate very large integrated gene networks."

"You can't take a complex neuropsychiatric disease that has escaped our understanding for 50 years and in one fell swoop have a therapy that is going to reverse it — that's folly. On the other hand, we now have clues to the neurobiology, the genetics, and the epigenetics of autism. To move forward, we need to invest more money in basic science to look at the genome and the epigenome in a more focused way."

First and foremost, children think of it as fun and learn skills by doing what they enjoy.

PRT is effective in all of the child’s environments and versatile enough to use at home, in clinical settings, in an inclusive classroom, and in the community, and parents can easily start folding PRT strategies into the child's established routine right away.

How does PRT decrease stress for parents?

Children often hate having to perform drill practices involved with other autism treatments, they feel like they are being forced to do something they don't enjoy and they react to this by causing a scene to get out of treatment.

What exactly are "pivotal responses?"

"areas that are central to wide areas of functioning such that improvements occur across a large number of behaviors." 

Once they understand the connection between using their own words and getting something they want, they will start to use words spontaneously to communicate their needs. Mastering this one pivotal behavior, motivating the child to understand the connection between their own efforts to communicate with the outcomes of their efforts, will have an enormous ripple effect on other skills.

It works because there is a motivator that makes the child want to work to accomplish the task at hand, the reward for accomplishing the task has a direct connection to it.

PRT was named by the National Research Council of the National Academy of Sciences in 2001 as one of the top 10 state-of-the-art treatments for autism in the United States.

A child who is highly motivated to communicate and is having fun doing it will learn much more rapidly than a child who is not motivated and not enjoying what they are learning.

Look at the content of any intelligence test—language, arithmetic, patterns, designs. What we measure with the aid of those I.Q. booklets are not the abilities we inherited from out our animal past, but instead their exact counterpart; we measure only those skills the species has been adding throughout all its history since. In some sense, an intelligence test measures the modernness of an individual; an intelligence test measures an individual’s ability to appropriate for himself the same set of skills the species has been appropriating as a whole—skills that do not find their origin in our biological nature, but instead owe their existence to the strange, brewing mixture of non-biological pattern, structure and form that has been rapidly taking shape all around us.

The unusual characteristics of humanity’s transformational individuals are not the result of their genius, they are genius’s prerequisite

But counter to prevailing wisdom, there are many autistic individuals—most likely a majority—who do make substantial progress by means of an alternative perceptual course, a course that allows them not only to navigate meaningfully their surrounding world, but also to assimilate, if somewhat awkwardly and belatedly, to the human species itself (and thereby explaining how autism, estimated to be present in nearly one percent of the human population, could go entirely unrecognized until as recently as sixty-five years ago).

all autistic individuals must crystallize their existence by means of this alternative perceptual course—it becomes, in essence, autism’s most salient feature.

The unusual behaviors and interests of autistic children—lining up toys, staring at ceiling fans, twirling, flapping hands repeatedly, fascination with knobs, buttons, switches, letters, shapes and digits, watching the same video again and again, singing the same song over and over—these activities betray a form of perception completely unlike that of most other children, a perception noticeably absent in social and biological focus, but also noticeably drawn to symmetry, repetition and pattern.

The unusual routines of autistic children are the natural, indeed the expected, mode of expression for a form of perception engaged primarily by the structural aspects of the non-social, non-biological world.

Autistic individuals would have been the first to notice the inherent structure contained in the natural world—the geometry of plants, the isomorphisms of natural objects, the logic of the celestial seasons—only they would have had motivation to embrace such form, only they would have had the need to perceive nature’s symmetry, repetition and pattern in order to form their cognitive grounding.

We know only bits and pieces about the four Greeks on Professor Flynn’s list, but filling in with the traits from the list’s more modern members, we can reasonably summarize all the unifying characteristics: late- or strange-talking, socially awkward, irascible, obsessed with structure, compelled by form, unusually—not necessarily greatly—intelligent.

The continuing medicalization of autism, the insistent demonization of autism’s spontaneous effect—these carry the danger of an unforeseen consequence. For the cure of autism will not be the end of a tragic brain disorder; autism’s eradication will not see the passing of a troubling mental disease. The removal of autism from the entire human species will produce only an ironic solution to the mystery of our expanding human intelligence, it will produce the ignoble end to the Flynn effect.

When confronted by data that runs counter to our accustomed way of seeing things, we as humans have but two choices: we can try to explain the results away, or we can adjust our perception of the experienced world. The former choice paves the all-too-common road of modern academic science; the latter, as described above, walks the more promising path of genius.

Autism is not a mental illness, not a brain disorder, it is instead the source of humanity’s changing perception of its experienced world; it is, with care and understanding, genius’s fertile soil.

It found several genetic variants commonly associated with ASD, all of them pointing two specific genes found on chromosome 5 which control production of proteins which help cells stick to each other, and make nervous connections.

One variant, linked to a gene called CDH10, was so common - present in over 65% of cases of autism - that the researchers calculated that fixing it would cut the number of autism cases by 15%.

They also linked ASD rather less strongly to a group of about 30 genes which produce proteins that play a key role in enabling brain cells to migrate to correct places, and to connect to neighbouring cells.

Professor Simon Baron-Cohen, an autism expert at the University of Cambridge, said 133 genes had now been linked to the condition, and much work was needed to piece together how they interacted with each other and the environment.

The National Autistic Society said the exact causes of autism were unknown. In a statement, the society said: "There is evidence to suggest that genetic factors are responsible for some forms of autism. "However, the difficulty of establishing gene involvement is compounded by the interaction of genes and by their interaction with environmental factors. "Various studies over many years have sought to identify candidate genes but so far inconclusively."