Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

Vasoactive intestinal peptide

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Vasoactive intestinal peptide is a peptide hormone produced in the gut, the pancreas, and the brain. It has a number of different effects on the body:

  • With respect to the digestive system, VIP seems to induce smooth muscle relaxation (lower esophageal sphincter, stomach, gallbladder), stimulate secretion of water into pancreatic juice and bile, and cause inhibition of gastric acid secretion and absorption from the intestinal lumen. Its role in the intestine is to greatly stimulate secretion of water and electrolytes, as well as dilating intestinal smooth muscle, dilating peripheral blood vessels, stimulating pancreatic bicarbonate secretion, and inhibiting gastrin-stimulated gastric acid secretion. These effects work together to increase motility.
  • It also has the function of stimulating pepsinogen secretion by chief cells.
  • It is also found in the brain and some autonomic nerves. One region of the brain includes a specific area of the suprachiasmatic nuclei (SCN), the location of the ‘master circadian pacemaker‘. The SCN coordinates daily timekeeping in the bodyand VIP plays a key role in communication between individual brain cells within this region. Further, VIP is also involved in synchronising the timing of SCN function with the environmental light-dark cycle. Combined, these roles in the SCN make VIP a crucial component of the mammalian circadian timekeeping machinery.
  • VIP helps to regulate prolactin secretion. [Prolactin inhibits the sex drive]
  • It is also found in the heart and has significant effects on the cardiovascular system. It causes coronary vasodilationas well as having a positive inotropic and chronotropic effect. Research is being performed to see if it may have a beneficial role in the treatment of heart failure. VIP Wiki

Vasoactive intestinal peptide has been connected to autism. This is from a 2001 news report:

A new discovery by Nelson, Grether, and colleagues, however, may bring investigators even closer to the origins of autism than the cerebellum has.

They collected blood that had been taken from 246 subjects at birth and stored in a deep freezer. Of the 246 subjects, 69 had autism, 60 mental retardation, 63 cerebral palsy, and 54 were healthy controls. They then analyzed the blood samples for five different brain proteins—nerve growth factor, substance P, brain-derived neurotrophic factor, calcitonin gene–related peptide, and vasoactive intestinal peptide.

They found comparable amounts of nerve growth factor and substance P in blood samples from all four groups of subjects. However, they found much higher levels of the other three proteins in blood taken from subjects with autism and with mental retardation than in blood taken from the cerebral palsy subjects and healthy controls. And what was especially intriguing is that while about a quarter of the autism subjects did not develop symptoms of autism until they were at least 1 year old, they already had large amounts of these three proteins at birth.

Thus the three proteins may well play causative roles in autism, Nelson and her team concluded, and they believe their findings also suggest that autism is already present at birth or maybe even before. Some other evidence, in fact, also implies that this is the case, she pointed out.

For instance, if mouse-embryo brains are exposed to vasoactive intestinal peptide, they flourish; but if the brains are deprived of this protein, they do not grow properly. Vasoactive intestinal peptide is also known to be involved in the sleep-wake cycle, and autism patients often have sleep problems. Vasoactive intestinal peptide is also known to be made in the gut, and autism patients often have gastrointestinal problems. Small Steps Mark Progress in Understanding Autism

Symptoms of too much vasoactive intestinal peptide are likely to correlate with symptoms of VIPoma, which produces too much vasoactive intestinal peptide:

The major clinical features are prolonged watery diarrhea [..] and symptoms of hypokalemia and dehydration. […] Lethargy, muscle weakness, nausea, vomiting and crampy abdominal pain are frequent symptoms. Hyperkalemia and impaired glucose tolerance occur in < 50% of patients. During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely. VIPoma Wiki

Okay, hands up if you have autism and also have gastrointestinal problems, sleep problems, a dampened sex drive, acid reflux, and impaired glucose tolerance? If so, Occam’s razor suggests vasoactive intestinal peptide might be involved.

We investigated the vasoactive intestinal peptide receptor type 2 (VIPR2) gene as a candidate gene for autism. We searched for mutations in the VIPR2 gene in autistic individuals, and 10 novel polymorphisms were identified. Three polymorphisms in the upstream region were studied in detail, and there was no significant difference in the frequencies between the autistic group (n = 14) and unrelated controls (n = 52). The distribution of the genotypes in two of the three polymorphisms differed somewhat between autistic subjects with gastrointestinal problems and those without. Moreover, there was a trend showing a correlation between the genotypes for the third polymorphism and the severity of stereotypical behavior as ranked by the Gilliam Autism Rating Scale. These preliminary results suggest that VIPR2 may have a role in gastrointestinal symptoms and stereotypical behaviors in autism, although a larger collection of samples suitable for transmission disequilibrium tests is necessary to validate the results. A Study of Novel Polymorphisms in the Upstream Region of Vasoactive Intestinal Peptide Receptor Type 2 Gene in Autism

The symptoms are so similar to some people’s experience of food chemicals – particularly salicylates, that I suspect salicylates may work to aggravate underlying VIPR2 polymorphisms somehow.

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Written by alienrobotgirl

29 April, 2008 at 3:18 pm

Posted in Autism Genetics

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