Locus Coeruleus, Autism, and Noradrenaline

I’ve plugged the fact before that there’s a common anecdote about autistic children’s behavior being temporarily altered by fevers.

I ran across this interesting article on the brain region known as the “locus coeruleus” which apparently creates noradrenaline.

“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. (via.)

Bacteria playing their part in autism, diagnostic opportunity

“Gut bacteria may contribute to autism”

Children with autism appear to have a characteristic chemical signature in their urine which might form the basis of an early diagnostic test for the condition.

The finding also adds weight the hypothesis that substances released by gut bacteria are contributing to the onset of the condition.

Autism has previously been linked to metabolic abnormalities and gastrointestinal problems such as gut pain and diarrhoea. Several studies have also hinted at changes in gut bacteria in the faeces of children with autism. [...]

Using nuclear magnetic resonance (NMR) spectroscopy to analyse the children’s urine, they found that each of these groups had a distinct chemical fingerprint, with clear and significant differences between children with autism and unrelated controls.”The signature that comes up is related to gut bacteria,” says Nicholson. It is not yet clear whether the bacteria’s metabolic products contribute to the development of autism, but it is a possibility worth investigating, he adds. A large proportion of autistic children have severe gastrointestinal problems that tend to appear at about the same time as the behavioural symptoms.

“It adds another link to the gut bacterial involvement in the onset of disorder,” says Glenn Gibson of the University of Reading, UK, who has previously identified abnormally high levels of clostridium bacteria in children with autism.

One possibility is that the gut bacteria in children with autism are producing toxins that might interfere with brain development. One of the compounds identified in the urine of autistic children was N-methyl-nicotinamide (NMND), which has also been implicated in Parkinson’s disease.

Meanwhile, Derrick MacFabe of the University of Western Ontario in London, Canada, and his colleagues have found that short-chain fatty acids produced by clostridium bacteria can induce reversible autism-like behavioural and biochemical changes in rats. [...]

Even if bacteria are not actually contributing to the observed metabolic changes, they could still be put to use. “There is probably the basis of a test for autism based on a urinary metabolic profile,” says Nicholson. (via: 1,2.)

Shouts out to Dale for sharing this interesting link with me.

Increased serum levels of BDNF, reduced cerebellum levels in Autism

There is compelling evidence that led to the hypothesis of a role of BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. [...]

In this study the regulation of BDNF in the cerebellum of six autistic patients and six controls was studied by measuring the protein level of BDNF in post mortem tissues. The level of BDNF was significantly decreased in the autistic group compared to controls. Reduced BDNF in the cerebellum may be an indicator of aberrant brain development and growth in autism. (via.)

Additionally, the same page that quote came from had this little interesting tidbit about serotonin and autism.

Fewer 5HT2a (serotonin) receptors in pcc & acc in autistics

The posterior cingulate cortex (PCC) is activated when normal subjects see faces or hear voices of emotionally significant people in their lives; however, in autism the level of activation is impaired. [...]

The use of selective serotonin reuptake inhibitor (SSRI) medication has been shown to be successful in the treatment of autistic behaviors in some individuals. Serotonin (5-HT) has a role in neuronal development and has been extensively studied in autism with reports of excess 5-HT in the blood (hyperserotonemia) in some people with autism. [...]

The results show that there was a significant decrease in the density of one key type of serotonin receptor, the 5HT2A receptor, in the superficial cortical layers of the PCC in the adult autistic group when compared to age-matched controls. Similar results were found recently in the anterior cingulate cortex, an area involved in social-emotional processing. Evaluated together, these findings suggest that the 5-HT2a serotonin receptor decrease occurs in widespread cortical areas and may play a central role in some of the social deficits observed in autism. (via.)

Atypical Brain Functioning in Siblings of Autistics

Relative to the other groups, there was reduced activity in specific brain regions in children with ASD when they were watching biological motion compared with scrambled motion.

These included the right amygdala and the ventromedial prefrontal cortex, areas which other research has identified as having changed activity in adults with ASD.

The researchers found additional brain regions that showed reduced activity in both the siblings group and the ASD group, relative to the typically developing group.

They interpreted this result as a reflection of the underlying genetic vulnerability that the siblings group might have to ASD.

The scientists also found what they called “compensatory activity” in the siblings group – brain regions that were working harder than normal and might be helping the children overcome their increased genetic risk of ASD.

These included the right posterior temporal sulcus and the ventromedial prefrontal cortex, which have been implicated in social perception and social cognition. [...]

“More controversially, the authors also propose that other brain regions are under-responsive to biological motion in siblings of children with autism, as well as in those with autism.”

“Yet other regions are reported to be overactive in the siblings, and this is interpreted as compensatory activity.
“Since these siblings had no subclinical symptoms of autism, and were selected to have no other relatives with any autistic features, they are unlikely to constitute a group with strong genetic risk for autism, and so this aspect of the results is puzzling and it would be important to replicate it in another sample.” (via.)

It’s interesting that while autistics show below normal activation in the ventromedial prefrontal cortex, that their siblings showed above normal activation in the same region while viewing “biological motion.”

It’ll be interesting to see what mysteries of the human mind will be revealed as the diagnostic criteria for what exactly defines the autistic spectrum becomes more refined. Supposedly these autistic children didn’t have any other relatives showing symptoms of autism, however, wouldn’t it be interesting to find out whether their relatives show this same abnormal overactivation in said regions.

Autism & Vaccinations

I figured I’d just harvest a few links and give short excerpts:

Toxic metal clue to autism
“A study of mercury levels in the baby hair of children who were later diagnosed with autism has produced startling results. The babies had far lower levels of mercury in their hair than other infants, leading to speculation that autistic children either do not absorb mercury or, more likely, cannot excrete it.”

A link between thimerosal and the brain: Can vaccines affect central nervous system function?
“In their work, the scientists found that insulin-like growth factor-1 (IGF-1) and the neurotransmitter dopamine both stimulated folate-dependent methylation pathways in neuronal cells. At the same time they noted that compounds like thimerosal, ethanol and metals (like lead and mercury) effectively inhibited these same biochemical pathways at concentrations that are typically found following vaccination or other sources of exposure.”

Autoimmunity in autism
“Most reports of immunological abnormalities in autistic children have been from this subgroup of affected children, and the authors cite the increasing body of evidence for abnormal immune regulation and autoimmunity in autism. The initial observation of unexpected bowel pathology in autistic children came from the same group, and centered on pathology in the colon (Lancet 1998; 351: 637-641, American Journal of Gastroenterology 2000; 95: 2285-2295). Use of immunohistochemical techniques had suggested a novel form of colitis, in which the epithelium of the colon was particularly affected (Journal of Pediatrics 2001; 138: 366-372), and, thus, possibly suggestive of autoimmunity.”

Thimerosal, found in childhood vaccines, can increase the risk of autism-like damage in mice
“A new study indicates that postnatal exposure to thimerosal, a mercury preservative commonly used in a number of childhood vaccines, can lead to the development of autism-like damage in autoimmune disease susceptible mice. This animal model, the first to show that the administration of low-dose ethylmercury can lead to behavioral and neurological changes in the developing brain, reinforces previous studies showing that a genetic predisposition affects risk in combination with certain environmental triggers.”