Scientists at Albert Einstein College of Medicine of Yeshiva University have proposed a sweeping new theory of autism that suggests that the brains of people with autism are structurally normal but dysregulated, meaning symptoms of the disorder might be reversible.
The central tenet of the theory, published in the March issue of Brain Research Reviews, is that autism is a developmental disorder caused by impaired regulation of the locus coeruleus, a bundle of neurons in the brain stem that processes sensory signals from all areas of the body.
The new theory stems from decades of anecdotal observations that some autistic children seem to improve when they have a fever, only to regress when the fever ebbs. A 2007 study in the journal Pediatrics took a more rigorous look at fever and autism, observing autistic children during and after fever episodes and comparing their behavior with autistic children who didn't have fevers. This study documented that autistic children experience behavior changes during fever.
"On a positive note, we are talking about a brain region that is not irrevocably altered. It gives us hope that, with novel therapies, we will eventually be able to help people with autism," says theory co-author Mark F. Mehler, M.D., chairman of neurology and director of the Institute for Brain Disorders and Neural Regeneration at Einstein.
Autism is a complex developmental disability that affects a person's ability to communicate and interact with others. It usually appears during the first three years of life. Autism is called a "spectrum disorder" since it affects individuals differently and to varying degrees. It is estimated that one in every 150 American children has some degree of autism.
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.
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.
As evidence, the researchers point to a 2008 study, published in the Journal of Autism and Developmental Disorders, that found a higher incidence of autism among children whose mothers had been exposed to hurricanes and tropical storms during pregnancy. Maternal exposure to severe storms at mid-gestation resulted in the highest prevalence of autism.
Drs. Purpura and Mehler believe that, in 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.
"This gives us hope that we will eventually be able to do something for people with autism," he adds.
The researchers do not advocate fever therapy (fever induced by artificial means), which would be an overly broad, and perhaps even dangerous, remedy. Instead, they say, 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.
"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."
"The message here is one of hope but also one of caution," Dr. Mehler adds. "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."
The paper by Drs. Mehler and Purpura, "Autism, fever, epigenetics and the locus coeruleus," was published in the March issue of Brain Research Reviews.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island – which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein – the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training.
Deirdre Branley | EurekAlert!
Further reports about: > Autism > Brain > Brain Research > LC-NA > Medical Wellness > Medicine > Neural Regeneration > Neurotransmitter > brain region > brain stem > brain's noradrenaline > developmental disorder > disorders > dysregulated, meaning symptoms > epigenetic factors > fever > locus coeruleus–noradrenergic > new theory of autism > noradrenergic brain receptors
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
24.04.2018 | Life Sciences
24.04.2018 | Materials Sciences
24.04.2018 | Trade Fair News