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.