Please take a quick look at the “Neuron” link, so you can understand what a nerve and synapse look like, and where neurotransmitters are working. Depression affects 6.7 percent of the American population age 18 and older (more than 15 million people) in a given year. Clinical depression is a serious health problem, but depression is more than one thing, one condition. Someone who says they are depressed may be: experiencing grief, feeling blue or down, or may have hormonal problems like hypothyroid or impaired adrenal function.
Depressed and anxious people often have chronic digestive problems. 50% of Americans do. There is a strong brain-gut connection, which has to be addressed when dealing with neurons and emotions. Another thing to consider, especially with current or past digestive problems that have lasted many months or longer, is systemic candida. Candida can cause 50 different symptoms, including depression. Chronic viruses (Epstein-Barr Virus, Cytomegalovirus, HHV-6, Herpes I, Herpes II) can also cause depression.
Two things that have increased exponentially over the last 35 years are toxicity and inflammation. While it is rare, I have treated people with a low-grade inflammatory brain condition that was responsible for depression and anxiety.
Standard Psychiatric Diagnosis
There are about 310 diagnoses in DSM-5. They are useful, but it’s important to not take them as gospel truth. I believe there are about 15 - 20 major psychiatric diagnoses. As a metaphor let’s say each diagnosis has a shape. One’s a square, one’s a rectangle, and one’s a circle. From what I’ve heard from patients for decades, they often feel like their doctor has tried to get them to fit into a diagnostic category. Let’s say you are a “rectangle” and your doctor is trying to fit you into a “square hole.” It makes for quick, overly simplistic diagnosis.
AMINO ACID TESTING FOR DEPRESSION
The main neurotransmitters are norepinephrine, serotonin, dopamine, acetylcholine, glycine, glutamic acid, aspartic acid, endorphins, GABA and taurine. The first three neurotransmitters in this list are made “from” amino acids. GABA and taurine “are” amino acids. There are also hundreds of neurotransmitters called “neuropeptides,” which are short chains of amino acids.
Except for taurine, neurotransmitters are made by the conversion of precursor nutrients. Drugs can’t “make” a neurotransmitter. For example, L-tryptophan is the nutrient that makes serotonin. Medications work in various ways to increase the amount of a neurotransmitter in a synapse. SSRI antidepressants, like Paxil, Prozac, and Zoloft block the reuptake of serotonin from the neuron that created serotonin out of L-tryptophan. Here is what I believe is happening. Antidepressants may deplete the brain of the nutrients that actually make neurotransmitters. Unless an individual is replacing key nutrients through targeted supplementation or diet, neuron axon terminals are likely to get depleted of L-tryptophan (L-tyrosine, etc.). Every synapse involved with monoamines (serotonin, dopamine, norepinephrine, histamine) has an enzyme called “monoamine oxidase (MAO),” whose job is to break down excessive amounts of neurotransmitters in a synapse. Paxil may increase the amount of serotonin in a synapse, while MAO breaks down some of that excess serotonin. This may explain why a medication works for a person for a few months then stops working.
Current anti-depressant medications target serotonin or norepinephrine chemistry. If they worked 100% for you, you would not be reading this. The nutrient that makes serotonin is the amino acid L-tryptophan. The amino acid that makes dopamine and norepinephrine is the amino acid L-tyrosine. Amino acid therapy for depression is usually very effective and lacks the side effects that anti-depressant medications often cause.
Serotonin-deficiency can cause— depression, insomnia, carbohydrate craving, low self-esteem, obsessive thinking, eating disorders, and minor cognitive problems.
Norepinephrine-deficiency can cause— depression, insomnia, anxiety, fear, worry, impaired memory and concentration, and a host of other cognitive problems.
Dopamine-deficiency can cause — depression, lack of motivation, and low energy. Dopamine is involved with movement, motivated behavior, and helps us determine how relevant something is to our interests. Dopamine is associated with (or triggered by) cocaine, amphetamines, chocolate, and sexual orgasm. Medications have been developed that target norepinephrine and serotonin, but not dopamine. Low dopamine is not associated with anxiety. Clinical depression is associated with “psychomotor retardation,” a slowing of speech and movement. These symptoms may be related to low dopamine.
If dopamine is slightly elevated, a person might feel motivated and elated. If that elevation is moderate, an individual can experience “fear for no reason.” If dopamine is severely elevated, a person can experience paranoia and delusions. Obviously, balance is required. Too much or too little dopamine can cause problems.
Many people feel anxious and depressed. If the two are linked together, there is a good chance that both anxiety and depression are caused by deficient norepinephrine. For other people, anxiety and depression are not linked, so depression may be caused by low serotonin or norepinephrine, and anxiety may be caused by deficient GABA, our natural calming neurotransmitter. The picture is complex. We need to have the right amount of each neurotransmitter, but we also need the right ratio of one neurotransmitter to another.
AMINO ACID AND NEUROTRANSMITTER TESTING
The two most important tests for you are an amino acid test and a urine test for organic acids. Amino acids are the “input” side to brain chemistry. Most neurotransmitters are made from amino acids, which is why amino acid therapy is an important modality. If your amino acid test shows a deficiency in L-tyrosine, chances are good that your brain is deficient in norepinephrine and possibly dopamine, because those neurotransmitters are made from L-tyrosine. The amino acid phenylalanine also makes L-tyrosine.
The organic acids test, which Genova Labs calls “The Metabolic Analysis Profile” or MAP, is a urine test that examines 48 organic acids. This is the “output” side of brain chemistry. These organic acids are the breakdown products of 48 different, important biochemical processes. 8 of these 48 relate to neurotransmitters. The MAP includes testing for the breakdown products of norepinephrine, dopamine, and serotonin. If your VMA (vanilmandelic acid) or MHPG (3-methoxy-4-hydroxyphenylglycol) is quite low, it is likely that you are deficient in norepinephrine. On the other hand, if your 5-HIAA (5-hydroxy-indolacetic acid) is low, you have a deficiency in serotonin. If 5-HIAA is quite elevated, chances are that you have a chronic digestive problem. The digestive tract is a second brain, and when it’s stressed, it produces lots of serotonin. If homovanillic acid (HVA) is deficient, you are likely to be deficient in dopamine.
L-tyrosine enters the brain and is first converted into dopamine. With the right co-factors (vitamin C and copper), dopamine converts into norepinephrine. If HVA (dopamine’s byproduct) is elevated and VMA (norepinephrine’s byproduct) is deficient, you may not be converting dopamine into norepinephrine fast enough. If this is the case, supplementing with vitamin C and copper may lift this blockade and normalize both dopamine and norepinephrine. 2 to 4 milligrams of copper per day usually helps convert dopamine to norepinephrine. I rarely recommend more than 4 mg a day.
There are times when I order direct neurotransmitter testing. This issue has been debated but it is likely that blood platelet levels of neurotransmitters correspond to brain levels. I will order this test if I want an accurate reading of brain levels of GABA, acetylcholine, dopamine, and histamine to name a few. Acetylcholine, whose deficiency causes severe memory loss and a feeling as if someone pulled the plug on your mental energy, is the only neurotransmitter that is not made from amino acids. I may order a blood neurotransmitter panel, but Genova’s NutrEval, which includes amino acid analysis and urine organic acids, provides an enormous amount of information.
It is not enough to know which amino acids are too high or too low…and what your neurotransmitter levels are. Amino acid chemistry requires a number of important vitamin and mineral co-factors in order to get converted from amino acids into neurotransmitters. The active form of vitamin B-6 (pyridoxine) is P-5-P (pyridoxal-5-phosphate). P-5-P is an important cofactor for countless enzymes in our body. The enzymes that convert L-tyrosine into dopamine…and L-tryptophan into serotonin require P-5-P.
ABUSE, NEGLECT, AND PTSD
Trauma often causes depression and anxiety. The long-term effects of child abuse/neglect cause emotional problems that sound like “depression.” Trauma at any point in life can cause a great deal of suffering. Whether we are talking about adult survivors of abuse or wartime PTSD, it is important to understand underlying mechanisms. There are three survival mechanisms — fight, flight, and freeze. The freeze response is one of the most powerful biological mechanisms that keeps trauma from healing.To say it in a simpler way, the freeze response involves dissociation, or disconnection.
Trauma causes mental states that include depression as well as agonizing states that have no name. Some people feel “misery.” Trauma and the freeze response cause dissociation, a state in which people feel disconnected from self, others, nature, and/or God/Higher Power. Dissociation may sound like depression, but it is a lack of connection to everything, including emotion. Dissociation is not an emotion, but it can cause feelings of helplessness, isolation, loneliness, fear, anxiety, anger, and sadness.
When evaluating someone who feels depressed, I ask, “When did you first feel depressed? How old were you?” Adult survivors of abuse may say that they first felt depressed when they were young teenagers…or that they don’t remember any period when they were not depressed.
This person is biologically different from someone who grew up in a loving, intact home, functioned well in life, had good relationships, and then plunged into a deep, dark hole of depression when they were 40 or 50. This is a description of a “pure” biological depression.
If you are an adult survivor of abuse or neglect, you have probably been tried on numerous antidepressant medications as well as bipolar medications. I do my best to understand underlying mechanisms, and not treat people only by running through a DSM checklist. In is not my experience that medications have a lasting, positive effect on trauma-related depression. That does not mean that there are not problems with biochemistry. There are.
HOLISTIC APPROACH TO DEPRESSION
Depression is almost always caused by physical and mental/emotional factors. Whether you are depressed, have CFS, IBS, or cancer, there is always an emotional component, or what I call “the stress factor.” The stress factor includes: acute overwhelming stress, chronic stress, unresolved conflict, long-term effects of child abuse or neglect, and trauma at any point in life. Psychotherapy is part of my holistic approach, but it does not involve much talking. Rather it focuses on targeted Mental Fitness Techniques (meditation, use of the breath, interactive guided imagery, mood words, and BCTR (body-centered-trauma-resolution).
This page is mainly about the basic biochemistry of depression, but the “context” within which depression is occurring is important. When I look at all the components that make up a single human being, I’m looking at a lot of variables. If I treat 10 depressed people with similar age and a similar complex of symptoms, their lab work is going to be unique. If you are one of those 10 depressed people, the other 9 have biochemical patterns that are different from you. That’s why this approach is centered on the individual, his or her life, purpose, passion, exercise, strengths, weaknesses, relationships, diet, trauma history, creative outlets, and amino acid profile.
I deal with high levels of complexity…complexity of body, mind, and spirit. I take a very extensive history to gain the biggest picture I can. The lab work adds an enormous amount of solid data. Between lab work and your life history you are a very complex picture. My job is to make sense of that complexity. Generally, those thousands of pieces, or bits of information, form one coherent whole. Once we make sense out of the complexity, treatment is going to make much more sense than most people are used to. I won’t understand every piece of the puzzle at first, but over time the pieces will come together. My job is to analyze great complexity, and then explain that complexity in the simplest, understandable terms for my patient. Healing takes place within a context. What I’ve just shared is the context. — Dr. David Gersten
