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By William J. Walsh
Skyhorse PublishingCopyright © 2012 William J. Walsh, PhD
All right reserved.
Chapter OneBIOCHEMICAL INDIVIDUALITY AND MENTAL HEALTH
History teaches that scientific progress is often blocked not by ignorance but by a widespread belief in something that isn't so. Advances in astronomy were delayed for centuries by assuming that the earth was the center of the universe. Johann Becher's phlogiston theory of combustion was accepted by chemists for nearly a century until Robert Boyle proved it to be false. J. J. Thomson's plum pudding theory of the atom blocked progress in understanding nuclear processes in the early 1900s.
The field of psychiatry has not escaped this malady. The misguided tabula rasa (blank slate) theory championed by English philosopher John Locke in the 17th century persisted as a central belief in psychiatry for 300 years. Locke revived Aristotle's theory that each newborn baby begins life with a "blank slate" with his/her personality and other mental qualities "written" on this slate by life experiences. The blank slate principle was expanded by Freud, Adler, and others who attributed depression, schizophrenia, and other mental disorders to traumatic events, especially those experienced in childhood. This belief led to highly popular psychodynamic therapies that reached their zenith in the 20th century. In 1960, the treatment of choice for mental illness involved a psychiatrist's couch and exploration of negative and positive life experiences. This protocol was dominant in psychiatry for more than 60 years, with benefits reported by millions of patients. However, the approach was very time-consuming and expensive, and progress was frequently partial in nature or nonexistent.
In the 1970s, the tabula rasa theory was proven to be fundamentally wrong, with clear evidence that babies are not born with a blank slate but rather with strong predispositions that affect personality and behavior. This understanding has led to a revolution in mental health, with a new focus on the biochemistry of the brain.
The Biochemical Revolution
Psychiatry research from 1950-1970 included several well-designed studies that examined the impact of life experiences on depression, bipolar disorder, schizophrenia, and other mental illnesses. The studies confirmed that a history of emotional or physical trauma, poverty, and deprived living conditions increased the likelihood of these disorders. However, this effort produced a surprising result—the discovery that the greatest predictor of mental illness was not life experiences but rather a family history of the same disorder. The most decisive results came from adoption and twin studies that confirmed the presence of powerful predispositions that could not be explained by tabula rasa. By the mid-1970s, most scientific and medical experts agreed that the dominant cause of most mental illness involved genetic or acquired chemical imbalances that alter brain functioning. Within a few years, psychiatry researchers changed their focus from life experiences to neurotransmitters, receptors, and the molecular biology of the brain.
It soon became apparent that brain chemistry is extremely complex and that clear understanding of the neurobiology of mental illness would require decades of research. With millions of mentally ill persons needing immediate treatment, the psychiatry profession turned to the only known method of altering brain chemistry—psychiatric medications. From the beginning, there were many seriously ill persons who benefited from these medications. Unfortunately, the improvements usually were partial in nature and resulted in serious side effects. Early medications included Prolixin, Mellaril, Haldol, and Thorazine, which frequently resulted in sedation, personality change, weight gain, loss of libido, and other nasty symptoms. Over the past 30 years, many improved medications have been developed, including selective serotonin reuptake inhibitor (SSRI) antidepressants and atypical antipsychotics. However, serious side effects continue to be reported for each of these newer medications, and there is little hope that future psychiatric drugs will ever be free of this problem.
It seems likely that advanced treatments in future years will utilize natural body/ brain chemicals that restore the patient to a normal condition rather than foreign drug molecules that result in an abnormal condition. The acceleration in scientific knowledge regarding neurotransmitters, receptors, and the molecular biology of the brain is greatly assisting achievement of this goal. The world will eventually learn the wisdom of Pfeiffer's Law: "For every drug that benefits a patient, there are natural substances that can achieve the same effect."
The Birth of Neurotransmitters
The human brain is an organ of extraordinary complexity. A typical adult has approximately 100 billion brain cells, with an average of 1,000 synaptic connections per cell. Every thought, action, and emotion involves communications between brain cells that are triggered by special chemicals called neurotransmitters. It is now generally accepted that most mental disorders involve imbalanced levels or altered functioning of these critically important brain chemicals.
In the 1970s, most research focused on a handful of neurotransmitters that were considered dominant in thought processes. Low serotonin activity was associated with clinical depression, elevated norepinephrine with anxiety, and elevated dopamine with schizophrenia. Other intensively researched brain chemicals included acetylcholine, aspartic acid, glutamate, and gamma-aminobutyric acid (GABA). Many additional neurotransmitters have been identified in the past 50 years, and it is believed that more than 100 are active in the human brain.
We do not receive a lifetime supply of brain chemicals at birth. Instead, the brain is a chemical factory that continuously produces serotonin, dopamine, and other neurotransmitters throughout our lifetime. Scientists have identified the brain locations where individual brain chemicals are synthesized and also defined the chemical reaction steps involved.
The Power of Nutrients
An underappreciated fact is that the primary raw materials for the synthesis of many neurotransmitters are nutrients—amino acids, vitamins, minerals, and other natural biochemicals that we obtain from food. Serotonin is produced from the amino acid tryptophan, a constituent of protein, and the final reaction step requires vitamin B-6 as a cofactor. Dopamine can originate from either of two amino acids with iron and folate also involved in the process. Norepinephrine is produced from dopamine with copper (Cu) having a decisive role. In another example, zinc (Zn) and B-6 are required for the synthesis and regulation of GABA. There are numerous other examples of the decisive role of nutrients in neurotransmitter synthesis.
Good mental health requires proper neurotransmitter activity at synapses. The dominant factor is reuptake, in which neurotransmitter molecules are whisked away from the synapse and returned to the original brain cell like a vacuum cleaner inhaling dust particles. This process is enabled by transporter proteins (aka transporters) embedded in the cell membrane that act as a passageway for the returning neurotransmitters. The population of transporters generally has a more dominant effect on synaptic activity than the number of neurotransmitters present. Transporters are continuously produced in the brain by genetic expression, the process by which information in a gene is used to produce a protein. The rate of production of transporters is enhanced by certain nutrients and inhibited by others. For example, methylation (addition of a CH3 chemical group) of DNA is a primary mechanism for "silencing" (switching off) genes that produce neurotransmitter transporters. The net result is that undermethylated persons generally have reduced serotonin activity and a tendency for depression. In another example, overmethylated persons may have excessive dopamine activity and a tendency for anxiety and paranoid schizophrenia. Nutrient therapy to adjust methyl levels can produce major benefits for these patients by normalizing the synaptic activity of these important neurotransmitters.
There are a multitude of genetic and environmental aberrations that can produce nutrient imbalances in the brain. If the brain is presented with a severe overload or deficiency of a nutrient required for neurotransmitter synthesis or activity, one can expect that mental problems will result. This understanding has given rise to a new medical approach for the treatment of depression, anxiety, and other types of mental illness called biochemical therapy or nutrient therapy. The primary elements involve (a) diagnosis of nutrient imbalances through testing of blood, urine, and tissues, and (b) therapies aimed at normalizing nutrient levels in the brain.
Each of us has innate biochemical factors that influence traits such as personality, behavior, mental health, immune function, and allergic tendencies. The number of different genetic combinations possible in a child from the same two parents exceeds 40 million. Human beings are not a combination of their mother and father but possess physical characteristics and traits from a genetic lottery involving many ancestors. Except for identical twins, each human being has unique biochemistry, resulting in quite diverse nutritional needs. Shakespeare was correct when he wrote "One man's meat is another man's poison." For example, some of us are genetically suited for a vegetable-based diet and others are not. Some persons can satisfy their nutritional needs by diet alone, and others must have nutritional supplements in order to overcome genetic aberrations.
A major breakthrough in medical science was the concept of biochemical individuality developed by Roger Williams in the 1940s. Williams, the discoverer of the B vitamin pantothenic acid, was renowned for his pioneering research on folic acid and other vitamins. However, his greatest contribution may have been the discovery that many persons are born with nutrient imbalances that play a role in heart disease and other disorders. This breakthrough has inspired many researchers to study the biochemistry of diseases and to investigate biochemical therapies aimed at correction of nutrient imbalances. Williams founded the Clayton Foundation Biochemical Institute in Texas that continues as a world leader in nutrition science.
It is now clear that abnormal levels of key nutrients can have an adverse effect on brain chemistry and mental health. Because of these abnormalities, some individuals have a predisposition for conditions such as clinical depression, oppositional defiant disorder (ODD), and attention-deficit/hyperactivity disorder (ADHD), while others are quite invulnerable to these disorders. Biochemistry can be affected by diet and stressful life events, but the dominant factor often goes back to genetics or, additionally, epigenetics. The concept of epigenetics will be addressed more thoroughly in Chapter 4, but very briefly, the environment (e.g., diet, toxins, lifestyle) can affect the expression of a person's genes, and this alteration in gene expression is called epigenetics. Epigenetics explains why one identical twin may manifest a particular disease, while the other does not.
A comprehensive metabolic analysis of any person would likely reveal several nutrients that are deficient due to genetics. Some deficiencies might be of minor importance with respect to human functioning, while others could result in serious mental problems. If people knew which nutrients were deficient, they might benefit greatly from many times the recommended daily allowance (RDA) of those nutrients since they may be fighting a genetic tendency for deficiency.
After clinical experience with thousands of mental health patients, I was surprised to learn that nutrient overloads usually cause more mischief than deficiencies. This explains why most multivitamin/mineral products are ineffective for mentally ill patients and can cause more harm than good. Patients with an overload of copper, methionine, folic acid, or iron are likely to deteriorate if they take supplements containing these nutrients. In most cases, mentally ill persons cannot become well using a special diet or indiscriminately stuffing themselves with amino acids, vitamins, and minerals.
The challenge is to carefully identify the specific nutrient overloads and deficiencies possessed by an individual and to provide treatments that normalize blood and brain levels of these chemicals with rifle-shot precision. This is the essence of biochemical therapy.
Chapter TwoBRAIN CHEMISTRY 101
The Chemical Symphony of the Brain
Every perception, thought, emotion, action, and memory involves a complex symphony of chemical processes in the brain. The sciences of neuroanatomy and neurochemistry have achieved great progress in the past 200 years, resulting in a basic understanding of the structure of individual, tiny brain cells and the chemical events that dominate brain function.
Brain cells were discovered in the early 1800s by Jan Evangelista Purkinje, Carmillo Golgi, and others using high-magnification microscopes and tissue staining methods. For several years, it was believed that brain cells (called neurons) were directly wired together forming a complex electrical circuit. However in the 1880s, Spanish scientist Ramon y Cajal discovered that neurons didn't actually touch but communicated by sending signals to nearby neurons. At first, the signals were described as sparks that jumped from neuron to neuron. In the 1890s, Charles Sherrington's laboratory in England developed convincing evidence that the transmission was chemical in nature and occurred across a tiny gap between brain cells that he called a synapse from the Greek word meaning "to clasp."
In 1921, Austrian scientist Otto Loewi discovered the first neurotransmitter, which is now known as acetylcholine. Many dozens of neurotransmitters have been identified among the more than 100 in the human brain. Much research has been devoted to neurotransmitters that are associated with specific mental disorders including depression (serotonin), schizophrenia (dopamine, glutamate, serotonin), anxiety (norepinephrine, GABA), and Parkinson's disease (dopamine).
Neurons are cells that receive, process, and transmit electrochemical signals at a speed of about 200 mph. In addition to the approximately 100 billion neurons in the brain, glial cells provide structural support and nourishment for the neurons and are far more numerous than neurons. Most neurons vary in size from 4 microns to 100 microns in diameter. Their length varies from a fraction of an inch to several inches. As shown in Figure 2-1, neurons consist of a cell body with branching dendrites (signal receivers) and a long, wire-like projection called an axon, which conducts the nerve signal. The axon terminals transmit the electrochemical signal across a synapse (the gap between the axon terminal and the receiving cell).
The neuron's nucleus contains the individual's DNA, which is neatly wrapped around tiny proteins called histones. A typical neuron has 1,000 hair-like dendrites branching from the cell body with a receptor at each terminal that can receive chemical messages from nearby brain cells. A typical human brain has approximately 100 trillion receptors. The axon is coated and insulated by a substance called myelin, which consists of 70-80% lipids (fat) and 20-30% protein.
Brain neurons act as tiny battery cells that are free-floating; in other words, in most cases, they do not actually touch other neurons. They typically develop a resting voltage of about 1/15 volt from ion concentration gradients across the membrane. When activated, the neuron acts as a miniature gun that shoots neurotransmitter molecules into a synapse. Like snowflakes, no two neurons are exactly alike. They differ in shape and the voltage threshold needed to fire. A neuron will switch on only if its resting threshold voltage is exceeded. Each neuron receives a multiplicity of inputs from its dendrite receptors, some that promote cell firing and others that are inhibitory. When a neuron fires, an electrochemical pulse called an action potential is sent down the axon to the terminus, releasing neurotransmitter molecules into the synaptic space. Some of these molecules link with receptors of nearby cells, sending an activating signal to that cell. This is the basic way in which brain cells communicate with each other. If a sufficient number of brain cells are activated, a thought or action can result.
A neuron that sends a signal across a synapse is called presynaptic, and the neuron that receives the signal is termed postsynaptic. The receptors themselves may be thought of as hunks of protein embedded in the membranes of neurons. Most receptors have a unique configuration that can receive a signal from only one type of neurotransmitter. In general, a serotonin receptor can be activated by serotonin molecules alone and not by other brain chemicals.
The Neurotransmitter Life Cycle
Most neurotransmitters are produced by chemical reactions in brain cells. After a period of service, they are chemically degraded. The life cycle steps are as follows:
1. Synthesis (generation by chemical reaction)
2. Packaging into vesicles
3. Release into a synapse
4. Interaction with an adjacent cell
5. Reuptake (transport back to the original cell for reuse)
6. Death (deactivation by chemical reaction)
Step 1: Synthesis: Most neurotransmitters are produced in the axon terminus near the synapse. The reactants consist of (a) amino acids and other nutrients that enter the cell through the cell membrane, and (b) enzymes that are produced by gene expression in the nucleus and make the long journey down the axon via microtubule tunnels.
Step 2: Packaging into vesicles: Vesicles are storage units that resemble tiny bubbles swimming in the cell liquid (cytosol). They are also formed in the nucleus and travel down the axon via microtubule tunnels. Neurotransmitters are loaded into vesicles through proteins called vesicular monoamine tranporters (VMAT) that are embedded in vesicle membranes. About 20 to 200 neurotransmitter molecules can be stored within each vesicle. Some of the vesicles attach to the neuron's membrane at docking sites where they can launch their neurotransmitters into the synapse.
Excerpted from Nutrient Power by William J. Walsh Copyright © 2012 by William J. Walsh, PhD. Excerpted by permission of Skyhorse Publishing. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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