Depression refers to a mental condition that is characterized by several symptoms that include but are not limited to: lethargy, isolation, prolonged periods of sadness, sudden emotional outburst such as crying for no particular reason, bouts of rage, self destructive tendencies such as cutting or biting, anxiety, paranoia, loss of appetite or unusual increase in appetite characterized by binge eating, insomnia and hostility. Recent estimates indicate that 1 out of every 10 individuals in the United States in termed as clinically depressed. The study also found that those likely to e depressed are: persons without any source of income, those who have had a marriage end in divorce, blacks, Hispanics and persons aged between 45 and 64. There are several causes of depression. Life events such as loss of a loved one, loss of a job, sexual assault, traumatic experience trigger psychological depression. This form of depression tends to evaporate with time if the individual seeks psychological help for their condition.
However depression that stems from biochemical causes tends to be more persistent. It therefore requires to be addressed through the use of drugs. Some of the biochemical causes of depression include; excessive sugar and caffeine use: hypoglycemia , neuro-transmitter depletion of norepinephrine or serotonin, essential fatty acid imbalances in the brain , systemic buildup of fungal molds, Candida yeast other nutrient deficiencies or dependencies, , histadelia (abnormally elevated histamine), hypothyroidism, brain allergy reactions to foods and cerebral sensitivities to airborne chemicals, Brain damage from alcohol or drugs and buildup of heavy metals in the brain e.g mercury.
This paper analyses the biochemical aspect of depression, its effects on the body and the brain and the treatment available for the different causes of depression.
1.0 Neurotransmitter depletion theory
This theory was first advanced in the 1950’s. Depression is as a result of a deficiency in the monoamine dependent neuro-transmitters. As a result of this deficiency, there is a decline in the levels of serotonin. Serotonin is known to control sleep, moods, hormonal functions and emotional behaviour hence depletion in its levels results in a decline of these functions. Evidence of the link between depression and serotonin levels stems from the fact that drugs which selectively affect serotonin have been effectively used in the treatment of depression. . Selective serotonin reuptake inhibitors (SSRIs) have used successfully as antidepressants due to their potent inhibitory effect on the reuptake of serotonin but very little effect on the reuptake of other monoamines or on other neurotransmitter receptors.
There is also evidence to suggest that noradrenalin plays a role in depression. This is due to the fact that serotonergic and noradrenergic neurons are known to be closely linked. This is further evidenced by the fact that the inhibition of the up take of serotonin tends to have an effect on the levels of noradrenalin.
2.0 Role of essential fatty acids in depression
The proper function and balance of serotonin and noradrenalin which both have a role in controlling emotional behaviour is dependent on the presence of the right quantity of essential fatty acids. Essential fatty acids make up over 60% of the brain thus are required in the proper amounts for the brain to function properly. Omega 3 and Omega 6 are both important in the functioning of neurotransmitters but Omega 3 plays a more important role. Research involving patients with long term depression has shown that including foods rich in Omega 3 has helped in treating their depression which in some cases has been a life long problem.
In countries such as Ireland, United States of America and Scotland where consumption of hydrogenated fats is high, the statistics also show that the number of people with depression is also high. This is because the hydrogenation of fats tends to deplete Omega 6 oils. Gamma linolenic acid, an Omega 6 essential fatty acid has been used in some studies as a supplement for depressed patients with remarkable stories of recovery being recorded.
3.0 Vitamin deficiency and mineral depletion as a cause of depression
In a study conducted at the John Hopkins University, it was discovered that over 69% of the study subjects had exhibited depression prior to their death but they had undiagnosed scurvy. B complex vitamins have an essential role to play in mental and emotional well being. Recent studies have shown the link between B complex deficiency and depression as outlined: Vitamin B1 deficiency results in depression and triggers neurological ad craniological disorders. Further evidence of the role of B complex vitamin in mental well being is provided by a recent study by the British Journal of Psychiatry which indicates that almost 98% of the patients that were admitted at a psychiatric ward were deficient of riboflavin. A deficiency of pyridoxine results in the disruption of the formation the anti-depressant neurotransmitters. Vitamin B6 is the co-enzyme required for the conversion of tryptophan to serotonin, and phenylalanine and tyrosine to norepinephrine.
4.0 Role of mineral deficiencies in causing depression
There are several minerals that are required in proper amounts for the emotional well being. These include but are not limited to: calcium, potassium, magnesium, zinc, manganese and magnesium. A deficiency of magnesium results in depressive tendencies as discovered in a study conducted by the American Medical Association. Depression is often a symptom associated with chronic iron deficiency. Other symptoms include lack of appetite, weakness, listlessness, exhaustion and headaches.
Depletion of potassium is often associated with depression and fatigue. In one study it was found patients suffering from depression are more likely to have decreased intracellular potassium. Decreased brain levels of potassium were also found in autopsies conducted on suicide cases .Manganese is required for proper utilization of the B-complex vitamins and Vitamin C. Given that it also has a role in the formation of amino – acid a deficiency may contribute to depression as a result of low levels of the anti-depressant neurotransmitters (serotonin and norepinephrine.) Manganese is vital in stabilization of blood sugars therefore prevents hypoglycemic mood swings.
5.0 Hypothyroidism as a Cause of Depression
Hypothyroidism is a condition that occurs when the thyroid gland, that is located in front of the neck just below the larynx (voice box), fails to secrete sufficient amounts of the hormones T3 (tri-iodothyronine) and T4 (thyroxine). The defects in the thyroid gland itself or the pituitary gland and hypothalamus, both of which control the secretion of T3 and T4, could be a cause of hypothyroidism. This condition is characterizes by fatigue, intolerance to cold, constipation, joint or muscle pain and depression. In order to treat hypothyroidism, medication can be administered to replace the missing thyroid hormone leading to an improvement of both emotional and physical symptoms. Studies have shown thyroid can act as an antidepressant and perhaps also as a mood stabilizer.
6.0 Hypoglycemia as a cause of depression
Conversion of one brain molecule into another form , for example changing of tryptophan into serotonin, sufficient amounts of Adenosine Triphosphate (ATP) are required . That energy is obtained from the sugars, often glucose. Through the glycolytic pathway, it undergoes conversion into other forms resulting in the production of ATP molecules as a by product. Although the brain only makes up 2% of the body, it uses between 60% and 70% of the generated energy about at any given time. To fuel all the intracellular biochemical reactions a healthy cell needs approximately two million ATP molecules per second. Therefore if the brain is denied energy, it is not able to generate neurotransmitters such as acetylcholine, norepinephrine, serotonin, or dopamine which are responsible for controlling emotions, particularly those associated with happiness and calmness.
An immediate consequence of hypoglycemia is that the body overproduces stress hormones, which in turn reduces the person’s self-esteem, a component of depression. Insufficient amounts of serotonin in the body result in inadequate production of melatonin - the neuro-chemical responsible for inducing sleep. For this reason depression is often linked with sleeplessness (insomnia). Given the association between serotonin and the mechanism of appetite, depression is more often than not associated weight problems.
7.0 Excess sugar consumption and depression
Conversion of excess sugar to glucose predisposes the cellular DNA and the immune system to attack by free radicals. This is attributed to the ease with which glucose is oxidized into toxins such as peroxides. In response to this the body shuts down insulin receptors which control the uptake of glucose into cells. This phenomenon is known as insulin resistance, which often leads to symptoms characteristic of hypoglycemic. There are several studies that show a significant link between insulin resistance and depression. As a result of insulin resistance the blood sugar levels increase, initiating increased secretion of insulin ( hyperinsulinism) and this may trigger an abrupt decrease in level of blood glucose. Therefore the brain is prone to a wide range of blood sugar level fluctuations, that are associated with several ‘psychological’ symptoms.
8.0 Candida infection and depression
An unchecked multiplication of yeast results in the secretion of toxins which circulate throughout the body therefore weakening the immune system. The Candida (yeasts and fungus) tend to multiply when a person’s resistance has been lowered as a result of infection, nutritional deficiencies, allergies, or some other debilitating cause. The results of an abundance of these fungus toxins include depression, fatigue, loss of concentration, and aggravated PMS. In addition, they can also cause severe headaches and the weakening of immune system.
9.0 High histamine levels as a cause of depression
Histamines are chemical neurotransmitters found throughout the body that perform other functions besides the mediation of allergic reactions. Histamines play a vital role in regulation of the sexual libido, flow of tears and determination of the body's sensitivity to pain. It is possible to have too much of histamine as in histadelia. Histadelia is a condition characterized by excessive levels of histamine in the blood. It is usually a genetic condition which manifests when the patients are about 20 years. The high levels of histamine increases the level of metabolism thus, patients are most often thin. Symptoms of histadelia include increased production of saliva and mucus, compulsive behavior, hyperactivity, sparse body hair, easy sexual orgasm, light sleep and depression. According to research histadelics make up most of the problem patients in psychiatric wards.
The most common treatment for high histamine depression is in the form of daily doses of methionine. Patients typically take one 500 mg capsule of methionine four times daily. This amino acid methionine, aids in the neutralization of the effects of excessive histamines through methylation of the brain's ring structure which is critical in the production of histamines.
Many of these additives that are found in food are classified as Excitotoxins. They enhance the taste or flavor of food by releasing glutamic acid or glutamate in addition to aspartic acid and cysteine which are brain-active amino acids. A well known example of an excitotoxin is MSG or mono-sodium glutamate. High blood levels of this excitotoxin can cross the highly protective blood-brain barrier. Glutamate is a neurotransmitter that is found in the extra-cellular fluid at low concentrations. If the concentration is inappropriately raised then neurons fire abnormally eventually resulting in the death of brain cells at higher levels. Inadequate amounts of oxygen and lack of fuel (hypoglycemia) both interfere with the production of energy in the brain cells, a factor that has been known to contribute to depressive tendencies.
Amino acids that have excitotoxins which cause problems mainly when they are used either in high concentrations. Majority of the processed foods contain excitotoxins, particularly if any kind of commercial taste or flavor enhancers have been included such as yeast extract, hydrolyzed vegetable protein, commercial soups, soy protein extract, , beef stock and caseinate. Aged proteins, processed meat, cheeses and tomato puree have greater levels of free glutamate as compared to fresh produce. All of these should be avoided by sensitive individuals who are prone to overactive mental conditions.
Research has shown that specific protein fragments (peptides) from wheat, cows' milk and bacterial decomposition products have an adverse effect on the chemistry of the brain triggering the so-called cerebral allergy. This may then express itself in a wide range of mental and emotional disorders. If the intestinal wall has been damaged by increase in gluten intake, by local inflammations due to Candida, food allergy, and also by the frequent use of aspirin and similar drugs, then bacterial and fungal breakdown products from the normal intestinal flora may be absorbed.
11.0 Mercury exposure as a cause of depression
Continued exposure to mercury has been known to cause depression and anxiety. Acute exposure is known to cause chronic depression, anxiety, and obsessive-compulsive behaviour. Studies also indicate people suffering with depression and major neurological diseases have established that chronic mercury poisoning from dental amalgam fillings could play a crucial role in the development of these conditions.
There are various ways in which chronic mercury poisoning can result in depression as outlined below:
Inhibition of the production energy by inhibiting mitochondrial respiration
Mercury interferes with and alters the actions of essential minerals such as magnesium and zinc which act as cofactors in enzyme reactions. Subnormal levels of zinc have been linked to treatment-resistant depression and low levels of magnesium have been associated with a wide range of psychiatric symptoms ranging from apathy to psychosis.
Direct damage to the neurons (nerve cells)
Disruption of the synthesis, release and binding of brain neurotransmitters such as dopamine, noradrenaline (norepinephrine) and serotonin which control emotions Promoting widespread oxidative damage and inflammation throughout the nervous system
Mercury can inhibit the function of the astrocytes in the central nervous system which are responsible for provision of vital nutrients to the neurons, damage repair and the maintenance of the blood-brain barrier
The presence of high levels of mercury in the blood can trigger the activation the microglia cells in the brain. These cells secrete large amounts of neurotoxic substances such as glutamate that enhance inflammation of the brain in addition to triggering the stimulation of the region of brain associated with anxiety
Inhibiting the neurotransmitter, acetylcholine which is involved in impulse control leading possibly to suicide, aggression and compulsive and/or obsessive behaviours
Causing a dysfunctional digestive system resulting in the overgrowth of yeasts such as Candida albicans. These yeasts secrete several toxins including ethanol and acetaldehyde that trigger direct depressive effects upon the brain of their host.
It can lead to the depletion detoxification via substances such as glutathione and thiols which leads to increased toxicity of the nervous system
Mercury can cause dysfunction in glucose metabolism which leads to cravings for substances such as carbohydrates and alcohol. The high sensitivity of the brain decreased or poorly controlled glucose levels are known to cause depression
Alcohol and substance abuse as a cause of depression
Alcohol, commonly abused street drugs such as heroin and cocaine drugs and prescription drugs have a common feature: They deplete the body and brain of essential natural chemicals such as serotonin and noradrenaline which are responsible for emotional well being. Those who attempt to cease from using these drugs often encounter .Most alcohol and drug addicted persons who stop their use still experience cravings, depression, anxiety, and unstable moods. The absence of buffer of drugs results in a heavy burden being borne by the nervous system and the brain. During a study that was carried out for a period on about ten years it was found that alcoholics tend to experience the following during and even in the period that they try to abstain from abuse of alcohol: Depression, hostility, anxiety, paranoia, psychosis, phobia, inadequate and inferior feelings.
12.0 Treatment of depression and recommendations
According to the U.S. Preventive Services Task Force suggests that health-care providers ought to screen adults for depression once the programs are up and running to ensure that accurate diagnosis and effective treatment is available along with careful monitoring and follow-up of the patients . The Task Force on Community Preventive Services also recommends a shift from the traditional approach to collaborative care. In this approach there is collaboration of primary care providers, mental health specialists and other providers in order to come up with better approaches for disease management for depressed adults and youth based on strong evidence how effective treatment can be in improving short-term depression outcomes.
In addition, sensitization programmes aimed at educating the public on the underlying causes of depression should be started in different countries. This would go a long way in preventing misdiagnosis of the cases of depression in addition to promoting a culture of early diagnosis. The mitigation measures should not just be limited to prescription of anti depressants which have become widely abused but should also include psychological care and a battery of tests to rule out all other causes.
National Institute of Mental Health. (2009, May 5). Depression. Retrieved October 21, 2011, from National Institute of Mental Health: http://www.nim.com
American Pscychiatric Association. (2009). Diagnostic and statistical manual of mental disorders. Washington: American Psychiatric Publishers Inc.
Devane, C., Chiao, E., Franklin, & Kruep., D. (2005). Anxiety disorders in the 21st century: status, challenges, opportunities, and comorbidity with depression. American Journal of Managed Care, 343-355.