Oxytocin and behavior

http://www.healing-arts.org/children/autism-overview.htm Oxytocin is produced through the influence of the cholecystokinin-A (CCKA) receptor, which requires its substrate, cholecystokinin, to be sulfated (see the free sulfate theory of autism). If there is insufficient ability to sulfate compounds (a finding in some autistic people), the receptor will not work well, and many CCKA mediated functions will be afffected. The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin has been well documented 6. Opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Both neuromodulators and a neurohormones co-exist in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, which serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system. Stress: Human immune function is mediated by the release of cytokines, nonantibody messenger molecules, from a variety of cells of the immune system, and from other cells, such as endothelial cells. There are Th1 and Th2 cytokines. Autoimmune and allergic diseases involve a shift in the balance of cytokines toward Th2. The autoimmune aspect of autism has been related to excessive Th2 cytokines resulting, in part, from vaccination. Gulf War syndrome and asthma have been similarly linked to excess immunization in the presence of increased environmental toxins and pollutants (high antigenic load). http://www.healing-arts.org/children/index.htm Please also see our new article, "Imaging Children with ADHD: MRI Technology Reveals Differences in Neuro-signaling". In this report, it was found that children with attention deficit-hyperactivity disorder (ADHD) may have significantly altered levels of important neurotransmitters in the frontal region of the brain, according to a study published in the December 2003 issue of the Journal of Neuropsychiatry and Clinical Neurosciences. "Our data show children with ADHD had a two-and-half-fold increased level of glutamate, an excitatory brain chemical that can be toxic to nerve cells," said lead author Helen Courvoisie, M.D., assistant professor, division of child and adolescent psychiatry, department of psychiatry and behavioral sciences at the Johns Hopkins Medical Institutions, Baltimore. "The data also suggest a decreased level of GABA, a neuro-inhibitor. This combination may explain the behavior of children with poor impulse control." Environmental factors associated with ADHD include low birth weight, hypozia (too little oxygen) at birth, and exposure in utero to a number of toxins including alcohol, cocaine, and nicotine. Other studies have found correlations between certain toxic agents / nutrient deficiencies and learning disabilities. These include: * Calcium deficiency * High serum copper * Iron deficiency can cause irritability and attention deficits * Magnesium deficiency, which is characterized by fidgeting, anxiousness, restless, psycho- motor inability, and learning difficulties * Malnutrition in general is related to learning disabilities; the child does not have to look malnourished, a fact forgotten in affluent countries * Dyslexic children seem to have abnormal zinc and copper metabolism - low zinc and high copper * Iodine deficiencies have been linked to learning difficulties http://osiris.sunderland.ac.uk/autism/owens.htm CHOLECYSTOKININ Lack of availability of sulfate would also seriously effect the performance of the major gut hormone and neurotransmitter called cholecystokinin. Two types of CCK receptors have been described: the first one, the CCKA receptor, is predominant in the alimentary canal; and the second, the CCKB receptor, is more abundant in the brain. Both receptors are found in both systems, however, and can be co-localized. (95,70) Many forms of CCK are active, but the octapeptide form of CCK which is a chain of eight amino acids, is able to promote the same degree of signal at the CCKB receptor regardless of whether sulfate has attached to it or not. On the other hand, the CCKA receptor is a thousand times more responsive to sulfated octapeptide than it is to the octapeptide's unsulfated form. (44,23) In a condition of low sulfate, CCK's maturation might be affected (24), and the delivery of its signal at the CCKA receptor would be unreliable.When one looks at the function of the CCKA receptor, the possible relevance to autism begins to become clear. Though it is clear there are some regions where the CCKA receptor does not regulate the production of serotonin, it clearly does have effects in the hypothalamus (34,56), and it is also clear that CCK has very powerful effects on serotonin in other regions where the receptor has not been differentiated. It may consequently have effects on serotonin's metabolite, melatonin, in the pineal gland. The CCKA receptor powerfully regulates dopamine(23,92,117); and also intrinsic factor (114), a substance in the digestive system which allows the body to absorb B12. When B12 is lacking it will result in elevations in methylmalonic acid in the urine (31), which was found to be consistently elevated in the children in Wakefield's recent study.(119) Dysregulation of these pathways in autism have been described by others. (7,82) The CCKA receptor also governs the release of oxytocin (64), dubbed "the social hormone" whose inadequacy may relate to the social deficits in autism. http://209.85.165.104/search?q=cache:NxDcVeCDi1EJ:www.eas.asu.edu/~autism/Additional/SummaryofDefeatAutismNow.doc+zinc+CCK+oxytocin&hl=en&ct=clnk&cd=3&gl=us Sulfation: Susan Owens substituted for Rosemarie Waring, and presented Dr. Waring's data on sulfate in autism. Basically, people with autism were found to excrete roughly twice as much sulfate in their urine, so that they had only 1/5 the normal level of sulfate in their bodies. Sulfur is an essential mineral, and is needed for many functions in the body. AIDS patients have also been found to exhibit a loss of sulfur in their urine, leading to a loss of extracellular sulfated structures in the brain. This has not yet been investigated in autism, but may be the same. In AIDS patients, treatment with N-acetyl cysteine was found to be beneficial. In autism, TNF (tumor necrosis factor) is elevated, which can inhibit the conversion of cysteine to sulfate. Low sulfur levels could cause many problems. o Sulfur is needed to sulfate the hormone CCK, which stimulates oxytocinergic neurons to release oxytocin. So, a lack of sulfur could explain the low oxytocin levels found in autism, which is important for socialization. o Sulphate is important for detoxification of metals and other toxins. o Sulphation requires activated sulfate, which requires magnesium. o Boys excrete more sulfur than girls, so they may be more susceptible to sulfation problems. o Wakefields group found that the ileum of the intestine lacks sulfur, which would lead to a leaky gut. o Sulphate is needed to release pancreatic digestive enzymes. o Many enzymes would be impaired if sulfur levels were low. o The perineuronal nets around neurons, which modulate their function, are primarily composed of chondroitin sulfur. Low sulfur would thus yield less modulation of neurons o The hepatitis B vaccine was found to inhibit sulphation chemistry for one week in typical people.

Oxytocin Deficits May Linger in Adopted Kids

Original Article MADISON, Wis., Nov. 22 - Children raised in the uncaring environment of some Eastern European orphanages ended up with a long-lasting deficit in two hormones involved in forming social bonds. In other words, nurture -- or the lack of it -- can trump nature when it comes to the ability to form social bonds, according to Seth Pollack, Ph.D., and assistant professor of psychology and of psychiatry and pediatrics at the University of Wisconsin. The deficits in oxytocin and arginine vasopressin persisted even after the children were removed from the orphanages and placed with loving and stable families in Wisconsin, Dr. Pollack and colleagues reported in the Nov. 21 online edition of the Proceedings of the National Academy of Sciences. The two hormones are known to play a role in the ability to form social bonds, Dr. Pollack said, and the deficit he and colleagues found is the first demonstration that early neglect can have a direct effect on neurobiology in ways that may later influence emotional behavior. Normally, Dr. Pollack said, infants begin to bond with caregivers almost immediately after birth and it is difficult to separate the influences of social experience and biology on such complex behavior. But the "aberrant social environments" of some orphanages in Russia and Romania -- where "a prominent lack of emotional and physical contact from caregivers" was standard -- provide a unique natural experiment, he and colleagues wrote. They compared 18 four-year-olds who had spent an average of 16.6 months in the orphanages and who were then adopted by families in Wisconsin to 21 children who were living with their biological parents. At the time of the study, the former orphans had been living with their new families for an average of 34.6 months. A baseline analysis showed that the former orphans began with markedly lower levels of vasopressin than the control children. The difference was statistically significant at p<0.01. That suggests, Dr. Pollack and colleagues said, that social deprivation may inhibit the development of the vasopressin system. Since the hormone appears to be critical for recognizing familiar people, that may in turn affect the formation of social bonds. There was no difference in the baseline levels of oxytocin, which is thought to confer a sense of security and protection. In the experiment itself, the children were asked to sit on the lap of a woman and play a 30-minute computer game that directed them to engage in various forms of physical contact, such as whispering, tickling, or patting each other on the head. Each child played the game twice, once with his or her mother and once with a stranger. After each game, the researchers collected a urine sample to measure oxytocin and vasopressin levels. The study found: • The control children tended to have higher levels of oxytocin than the former orphans after they interacted with their mothers. The difference approached statistical significance at p=0.056. • There were no differences between the groups after the interaction with the unfamiliar adult. • There were no differences in vasopressin between groups after either interaction. Dr. Pollack said the results may help explain why many neglected children have difficulties forming secure relationships, but added it should not be taken as evidence that the damage is permanent. "It's extremely important that people don't think this work implies that these children are somehow permanently delayed," he said. "All we are saying is that in the case of some social problems, here is a window into understanding the biological basis of why they happen." The researchers also noted that the findings don't apply to all adopted children; those in this study were subjected to an unusually deprived environment. Primary source: Proceedings of the National Academy of Sciences Source reference: Wismer Fries AB et al. Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc Nat Acad Sci. 2005;103: 17237-17240.

Sulfation, Enzymes, Oxytocin

http://209.85.165.104/search?q=cache:NxDcVeCDi1EJ:www.eas.asu.edu/~autism/Additional/SummaryofDefeatAutismNow.doc+zinc+CCK+oxytocin&hl=en&amp;amp;amp;amp;ct=clnk&cd=3&gl=us Sulfation: Susan Owens substituted for Rosemarie Waring, and presented Dr. Warings data on sulfate in autism. Basically, people with autism were found to excrete roughly twice as much sulfate in their urine, so that they had only 1/5 the normal level of sulfate in their bodies. Sulfur is an essential mineral, and is needed for many functions in the body. AIDS patients have also been found to exhibit a loss of sulfur in their urine, leading to a loss of extracellular sulfated structures in the brain. This has not yet been investigated in autism, but may be the same. In AIDS patients, treatment with N-acetyl cysteine was found to be beneficial. In autism, TNF (tumor necrosis factor) is elevated, which can inhibit the conversion of cysteine to sulfate. Low sulfur levels could cause many problems. o Sulfur is needed to sulfate the hormone CCK, which stimulates oxytocinergic neurons to release oxytocin. So, a lack of sulfur could explain the low oxytocin levels found in autism, which is important for socialization. o Sulphate is important for detoxification of metals and other toxins. o Sulphation requires activated sulfate, which requires magnesium. o Boys excrete more sulfur than girls, so they may be more susceptible to sulfation problems. o Wakefields group found that the ileum of the intestine lacks sulfur, which would lead to a leaky gut. o Sulphate is needed to release pancreatic digestive enzymes. o Many enzymes would be impaired if sulfur levels were low. o The perineuronal nets around neurons, which modulate their function, are primarily composed of chondroitin sulfur. Low sulfur would thus yield less modulation of neurons o The hepatitis B vaccine was found to inhibit sulphation chemistry for one week in typical people.

Oxytocin, Attachment and Biomed

http://www.healing-arts.org/children/autism-overview.htm Oxytocin is produced through the influence of the cholecystokinin-A (CCKA) receptor, which requires its substrate, cholecystokinin, to be sulfated (see the free sulfate theory of autism). If there is insufficient ability to sulfate compounds (a finding in some autistic people), the receptor will not work well, and many CCKA mediated functions will be affected. The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin has been well documented 6. Opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Both neuromodulators and a neurohormones co-exist in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, which serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system. Stress: Human immune function is mediated by the release of cytokines, nonantibody messenger molecules, from a variety of cells of the immune system, and from other cells, such as endothelial cells. There are Th1 and Th2 cytokines. Autoimmune and allergic diseases involve a shift in the balance of cytokines toward Th2. The autoimmune aspect of autism has been related to excessive Th2 cytokines resulting, in part, from vaccination. Gulf War syndrome and asthma have been similarly linked to excess immunization in the presence of increased environmental toxins and pollutants (high antigenic load). http://osiris.sunderland.ac.uk/autism/owens.htm CHOLECYSTOKININ Lack of availability of sulfate would also seriously effect the performance of the major gut hormone and neurotransmitter called cholecystokinin. Two types of CCK receptors have been described: the first one, the CCKA receptor, is predominant in the alimentary canal; and the second, the CCKB receptor, is more abundant in the brain. Both receptors are found in both systems, however, and can be co-localized. (95,70) Many forms of CCK are active, but the octapeptide form of CCK which is a chain of eight amino acids, is able to promote the same degree of signal at the CCKB receptor regardless of whether sulfate has attached to it or not. On the other hand, the CCKA receptor is a thousand times more responsive to sulfated octapeptide than it is to the octapeptide's unsulfated form. (44,23) In a condition of low sulfate, CCK's maturation might be affected (24), and the delivery of its signal at the CCKA receptor would be unreliable.When one looks at the function of the CCKA receptor, the possible relevance to autism begins to become clear. Though it is clear there are some regions where the CCKA receptor does not regulate the production of serotonin, it clearly does have effects in the hypothalamus (34,56), and it is also clear that CCK has very powerful effects on serotonin in other regions where the receptor has not been differentiated. It may consequently have effects on serotonin's metabolite, melatonin, in the pineal gland. The CCKA receptor powerfully regulates dopamine(23,92,117); and also intrinsic factor (114), a substance in the digestive system which allows the body to absorb B12. When B12 is lacking it will result in elevations in methylmalonic acid in the urine (31), which was found to be consistently elevated in the children in Wakefield's recent study.(119) Dysregulation of these pathways in autism have been described by others. (7,82) The CCKA receptor also governs the release of oxytocin (64), dubbed "the social hormone" whose inadequacy may relate to the social deficits in autism.