Delving Into The Autistic Brain - Part 4

What biochemicals are involved in the digestion and metabolism of the food we eat?

Carbohydrates, proteins and fats pass through the digestive tract from the mouth to the stomach and liver and onto the intestines. At each point along the way, these nutrients are acted upon by enzymes and hormones, protein chemicals that catalyze metabolic reactions.

Salivary amylase or ptyalin begins the digestion of starches and sugars in the mouth. Gastric juice, containing hydrochloric acid and the enzyme pepsin, starts to work on degrading proteins in the stomach. The acidic stomach contents then pass into the small intestine, where they are neutralized by bicarbonate secreted by the pancreas.

Pancreatic amylase continues the business of breaking down carbohydrate bonds and the process is completed by enzymes secreted through intestinal mucosal cell membranes. These cells in the lining of the small intestine also produce several small peptide hormones in response to the presence of fats (lipids) and partially digested proteins (polypeptides). One hormone, pancreozymin, acts on the gallbladder, causing it to release bile, and on the exocrine cells of the pancreas, causing them to release lipases and peptidases. Another intestinal hormone, secretin, causes the stomach to produce pepsin and the liver to produce bile. More significantly, it causes the pancreas to release bicarbonate solution that helps to neutralize the pH of the chyme emerging from the stomach so that pancreatic enzymes can do their job.

If all goes well, proteins are broken down into polypeptides and then into amino acids. Fats are hydrolyzed into glycerol and fatty acids, and carbohydrates are reduced from polysaccharides to monosaccharides (glucose, fructose and galactose). These metabolized nutrients pass through the portal vein in the liver before entering the circulation. The liver absorbs what it needs to synthesize glycogen, proteins and other nitrogen-based molecules and routes the rest to other tissues and organs, where substrates are further degraded and finally oxidized into energy in the form of ATP (adenosine triphosphate) and other byproducts including CO2, ammonia and water.

Why is the proper metabolism of protein so important?

Most of the amino acids released by the hydrolysis of dietary protein are used for the biosynthesis of tissue protein that is constantly being degraded. This process of protein synthesis and degradation is called protein turnover.55 If the amount of amino acids in the body’s amino acid pool is only adequate to meet the needs of protein turnover, due to insufficient dietary protein intake or incomplete metabolism, this shortage could result in a deficiency of nitrogen containing precursors necessary to form neurotransmitters, hormones and enzymes. An insufficiency of these chemical regulators or an abnormality in their formation would have serious consequences on the body’s and brain’s ability to function.

How do the brain and body communicate?

Located in the heart of the limbic system, the hypothalamus is in overall charge of regulating the body’s internal processes, including temperature, blood pressure and metabolism.56 The fuel needs of brain cells are communicated to the rest of the body by chemical signaling carried out by blood-borne hormones or by neurotransmitters released by the hypothalamus and pituitary gland.

Pituitary hormones act on other glands, including the thyroid, adrenals and sex glands, instructing them to release hormones. The level of hormones that feed back to the pituitary via the circulatory system signal the gland to either increase or shut off production of specific hormones. Neurotransmitters from the brain meet up with hormones from the body in the nerve fibers and portal blood vessels of the pituitary, enabling it to relay vital regulatory information up its stalk to the hypothalamus.57

One of the most important factors regulated by the pituitary gland and hypothalamus is the supply of glucose.

How is glucose formed and what function does it serve in the brain?

Glucose, which is catabolized into energy (in the form of ATP) is the primary fuel source for all body cells, including neural cells. Blood glucose is obtained from three primary sources: dietary carbohydrates, the degradation of liver glycogen and gluconeogenesis. In the absence of adequate dietary carbohydrates, or in the event that dietary carbohydrates are not properly digested and absorbed into the blood stream, glycogen stored in the liver and in muscle tissue can be converted into glucose. Glucose can also be synthesized from amino acids by a process called gluconeogenesis.

The glucose energy derivative ATP is used to fuel the brain’s electrochemical processes; to fire and receive nerve messages and synthesize and degrade neurotransmitters.58 If messages (in the form of neurotransmitter molecules) are not properly and smoothly relayed, information cannot travel to all the brain structures that need it to form the “big picture” of conscious experience.

Whether neurotransmitters bind with receptors or not, they have to be cleared away or broken down to prevent them from interfering with messages conveyed by subsequent releases of neurotransmitters.59 If neurotransmitters are not efficiently broken down or cleared away (due to a sluggish glucose energy supply) than receptor systems cannot be ready to receive and respond to new waves of impulses. This might account for many of the repetitive and perseverative behaviors of autism.

Which neurotransmitters might be implicated in the breakdown of information processing resulting in autism?

The brain chemical most commonly linked to autism is serotonin, although the largest amount of serotonin is actually found in cells of the intestinal mucosa.60 Outside the nervous system, serotonin functions to influence pain perception and to help regulate sleep, temperature and blood pressure. Studies have documented a significant elevation of blood serotonin in many autistic children, an abnormality attributable to an alteration in the uptake or storage of serotonin by blood platelets.61 In the brain this neurotransmitter is generally excitatory, meaning its release makes neurons more likely to “fire”. Serotonin releasing neurons have axons distributed throughout the brain from the cerebellum to the cerebral cortex.62 An excess of serotonin could account for the lack of modulation of sensory input, leading to overstimulation and anxiety.

The neurotransmitter Dopamine is also involved in modulating arousal level. The inability of schizophrenics to filter out incoming sensations is thought to be attributable to raised levels of dopamine in the brain or to the increased sensitivity of dopamine neural receptors which induce a high state of arousal.63 Autistic brains may be equally susceptible to over-stimulation due to the exaggerated effects of dopamine.

Uta Frith postulates that the problem could be attributable to dopamine cells not dying back as they should in normal development. The result would be an increased number of dopamine neurons and therefore an overactive system.64 As the major dopamine pathways or projections originate in tiny structures at the tip of the brain stem and spread out to almost every cortical lobe, the impact of this chemical on neurological processing could well be significant.

Two other neurotransmitters that may be implicated in autism are actually dopamine derivatives in the same catecholamine family. Unlike their precursor, norepinephrine and epinephrine have important physiologic functions outside the nervous system as well. They act as regulators of carbohydrate and lipid metabolism, increasing the degradation of triacyglycerol and glycogen to glucose as well as increasing heart beat and blood pressure in response to fright, exercise, cold and low levels of blood glucose.65 If there was a shortage of these “fight or flight” molecules in the blood (due to a problem with the catabolism of amino acids or dopamine) the breakdown of carbohydrates to glucose would be slowed, as would the body’s reaction to emergency situations.

In the brain, nerve cells that release norepinephrine are clustered in the brain stem with their axons projecting to many brain regions.66 As a neurotransmitter, norepinephrine is both excitatory and inhibitory and is involved in arousal level as well as in autonomic control of body functions. Norepinephrine as well as dopamine and serotonin have their effect on receptor cells through a time and energy consuming ‘second messenger’ system, so it is likely that any irregularity in the supply of glucose delivered to the brain would have a significant negative impact on the ability of these neurotransmitters to function smoothly.

Another brain chemical that might contribute to autism is GABA or gamma-aminbutyric acid. As this neurotransmitter is inhibitory, a deficiency of GABA in autistic children would help explain the poor inhibition that allows their brains to become overaroused and causes them anxiety.

Glutamate may also play a role in autism. Formed from glycogenic amino acids, this chemical acts as an excitatory neurotransmitter in the brain, activating some receptors in the hippocampus.67 If there is a problem with the formation of glycogenic amino acids, not only would there be a deficiency of glucose production, but there would be a deficiency of glutamate to activate receptors in the limbic system that influence emotion, learning, memory and motivation.68 Receptors in the amygdala, located directly atop the hippocampus, might also be affected, throwing off the coordination of autonomic and endocrine responses with emotional states.

How do drugs work to control neurotransmitter function?

All mind-affecting drugs have their action at the synaptic gap. They work by modifying the way neurons communicate across this gap. Some drugs alter the amount of neurotramsmitters released or the rate of release. Others have their effect by either blocking or increasing the availability of receptor sites. Others work by reducing the action of enzymes that break down neurotransmitters, rendering them inactive.69

The catecholamines (dopamine, norepinephrine and epinephrine) and serotonin are inactivated by oxidative deamination, catalyzed by the enzyme monoamine oxidase (MAO). MAO inhibitor drugs (antidepressants) serve to inactivate this enzyme, permitting neurotransmitter molecules to escape degradation and to activate dormant receptor systems. Some neurotransmitters are reabsorbed into axons from fluid surrounding the nerve cells for reuse (endocytosis). Drugs like fluoxetine or sertraline work by blocking the re-uptake or recycling of serotonin or norepinephrine, thereby reducing their excitatory effect on the brain.

How effective are drugs in remediating autism?

Just as in the typical population, various drugs have varying effects on individuals with autism. If we go by the assumption that autism has a biochemical basis, pharmacological intervention is certainly warranted and is often effective in alleviating the symptoms of excessive anxiety or obsessive-compulsive tendencies. Mega-doses of vitamins and minerals and other natural remedies found in health food stores are also helpful in many cases. I believe that any remedy that might help a person with autism to cope or function better is worth pursuing.

In my daughter’s case, the estrogen and progesterone in the birth control pills she takes have had a pronounced effect on her mood and behavior. Actually, progesterone is the precursor to all other steroid hormones, including estrogen, testosterone and adreno-corticotropic hormone or ACTH. The production and secretion of ACTH is activated by the hypothalamus when the body is stressed. This hormone stimulates the adrenal cortex to synthesize cortisol, which in turn acts to promote gluconeogenesis in the liver and to stimulate the breakdown of proteins to amino acids in the muscles. So, the ingestion of progesterone might not only cause an increase in ACTH, making a person better equipped to handle stress, but the increase in cortisol would activate glucose and amino acid synthesis, helping the brain and body to function better.

65 Pamela Champe; Richard Harvey, Lippincott’s Illustrated Reviews: Biochemistry, Philadelphia (1994) J.B. Lippincott Company, p. 230.

66 Pamela Champe; Richard Harvey, Lippincott’s Illustrated Reviews: Biochemistry, Philadelphia (1994) J.B. Lippincott Company, p. 47.

67 Susan A. Greenfield, The Human Mind Explained, New York (1996) Henry Holt and Company, p. 118.

68 Susan A. Greenfield, The Human Mind Explained, p. 118.

69 Pamela Champe; Richard Harvey, Lippincott’s Illustrated Reviews: Biochemistry, Philadelphia (1994) J.B. Lippincott Company, p. 288.

70 Susan A. Greenfield, The Human Mind Explained, New York (1996) Henry Holt and Company, p. 66.

71 Susan A. Greenfield, The Human Mind Explained, p. 60.

60 Pamela Champe; Richard Harvey, Lippincott’s Illustrated Reviews: Biochemistry, Philadelphia (1994) J.B. Lippincott Company, p. 265

72 Susan A. Greenfield, The Human Mind Explained, New York (1996) Henry Holt and Company, p. 67.

73 William Shaw, PhD, Biological Treatments for Autism and PDD, Shaw (1998) p. 130.

74 Pamela Champe; Richard Harvey, Lippincott’s Illustrated Reviews: Biochemistry, Philadelphia (1994) J.B. Lippincott Company, p. 277.

75 Pamela Champe; Richard Harvey, Biochemistry, p. 272.

76 Pamela Champe; Richard Harvey, Biochemistry, p. 252.

77 William Shaw, PhD, Biological Treatments for Autism and PDD, Shaw (1998) pp. 295-96.

78 Susan A. Greenfield, The Human Mind Explained, New York (1996) Henry Holt and Company, p. 66.