Depression

What is Depression?

Depression (major depressive disorder or clinical depression) is a common but serious mood disorder. It causes severe symptoms that affect how you feel; think; and handle daily activities such as sleeping, eating, or working. To be diagnosed with depression, the symptoms must be present for at least two weeks.

Some forms of depression are slightly different, or they may develop under unique circumstances, such as:

• Persistent depressive disorder (also called dysthymia) is a depressed mood that lasts for at least two years. A person diagnosed with persistent depressive disorder may have episodes of major depression along with periods of less severe symptoms, but symptoms must last for two years to be considered persistent depressive disorder.
• Perinatal depression is much more serious than the “baby blues” (relatively mild depressive and anxiety symptoms that typically clear within two weeks after delivery) that many women experience after giving birth. Women with perinatal depression experience full-blown major depression during pregnancy or after delivery (postpartum depression). The feelings of extreme sadness, anxiety, and exhaustion that accompany perinatal depression may make it difficult for these new mothers to complete daily care activities for themselves and/or for their babies.
• Psychotic depression occurs when a person has severe depression plus some form of psychosis, such as having disturbing false fixed beliefs (delusions) or hearing or seeing upsetting things that others cannot hear or see (hallucinations). The psychotic symptoms typically have a depressive “theme,” such as delusions of guilt, poverty, or illness.
• Seasonal affective disorder is characterized by the onset of depression during the winter months, when there is less natural sunlight. This depression generally lifts during spring and summer. Winter depression, typically accompanied by social withdrawal, increased sleep and weight gain, predictably returns every year in seasonal affective disorder.
• Bipolar disorder is different from depression, but it is included in this list because someone with bipolar disorder experiences episodes of extremely low moods that meet the criteria for major depression (bipolar depression). But a person with bipolar disorder also experiences extreme high moods —euphoric or irritable — called “mania” or a less severe form called “hypomania.”

Examples of other types of depressive disorders newly added to the diagnostic classification of DSM-5  include disruptive mood dysregulation disorder (diagnosed in children and adolescents) and premenstrual dysphoric disorder (PMDD). [1]

Signs and Symptoms

Those who have been experiencing some of the following signs and symptoms most of the day, nearly every day, for at least two weeks may be suffering from depression:

• Persistent sad, anxious or “empty” mood
• Feelings of hopelessness or pessimism
• Irritability
• Feelings of guilt, worthlessness or helplessness
• Loss of interest or pleasure in hobbies and activities
• Decreased energy or fatigue
• Moving or talking more slowly
• Feeling restless or having trouble sitting still
• Difficulty concentrating, remembering or making decisions
• Difficulty sleeping, early-morning awakening or oversleeping
• Appetite and/or weight changes
• Thoughts of death or suicide, or suicide attempts
• Aches or pains, headaches, cramps or digestive problems without a clear physical cause and/or that do not ease even with treatment

Not everyone who is depressed experiences every symptom. Some people experience only a few symptoms while others may experience many. Several persistent symptoms in addition to low mood are required for a diagnosis of major depression, but people with only a few — but distressing — symptoms may benefit from treatment of their “subsyndromal” depression. The severity and frequency of symptoms and how long they last will vary depending on the person and his/her particular illness. Symptoms may also vary depending on the stage of the illness. [2]

Risk Factors

Depression is one of the most common mental disorders in the U.S. Current research suggests that depression is caused by a combination of genetic, biological, environmental and psychological factors.

Depression can happen at any age, but often begins in adulthood. Depression is now recognized as occurring in children and adolescents, although it sometimes presents with more prominent irritability than low mood. Many chronic mood and anxiety disorders in adults begin as high levels of anxiety in children.

Depression, especially in midlife or older adults, can occur with other serious medical illnesses, such as diabetes, cancer, heart disease, and Parkinson’s disease. These conditions are often worse when depression is present. Sometimes medications taken for these physical illnesses may cause side effects that contribute to depression. A doctor experienced in treating these complicated illnesses can help work out the best treatment strategy.

Risk factors include [3]:

• Personal or family history of depression
• Major life changes, trauma or stress
• Certain physical illnesses and medications

What cause depressive disorders?

The cause of depressive disorders is unknown, but it is becoming clear that many of these disorders are caused by a combination of factors, including systemic diseases such as hypothyroidism, insulin resistance, hypoglycemia, leaky gut, or celiac disease, diet, abnormal intestinal bacteria, nutritional deficiencies, genetic mutations, previous life experiences, neurotransmitter imbalances, situational stress, and environmental stress.

Depression is not caused by a Prozac deficiency!

All the potential causes described above must be evaluated in someone complaining of depression. See thyroid disorders, insulin resistance, gastrointestinal health, and micronutrients for discussion of these conditions.

A very common mutation that may cause depression is the MTHFR (methyltetrahydrofolate reductase) mutation. Look at Figure 1.

At the top of the diagram from Dr. Ben Lynch is folic acid, a synthetic not found in nature. Dietary folate is in uncooked green leafy vegetables. Both of these have to be metabolized to 5-MTHF (5-methyltetrahydrofolate) for the body to use them effectively. When someone has the MTHFR mutation, the last step (where you see the X) is inefficient. The most common genes involved in this process are the C677T and the A1298C. If they are mutations in either of these genes, people are unable to produce adequate amounts of 5 MTHF for optimal metabolism. If they are given 5MTHF (a vitamin) combined with B2, B6, and B12, the frequencies of the conditions listed in Figure 2 are decreased, including depression.

The following cancers are reduced in frequency: breast, uterine, prostate, thyroid, stomach and colon. Depression, anxiety and schizophrenia are reduced as well.

The following neurotransmitter imbalances have been associated with depression:

• Low Serotonin
• Low GABA
• Low Norepinephrine

Low thyroid, low cortisol and insulin resistance may also cause depression.

Medications that cause mania or depression appear to alter brain chemicals in some way. And even though the drugs may be necessary to treat the condition, the side effect is hardly acceptable. As an example, isotretinoin (Sotret, Claravis), which is prescribed for the treatment of acne, has been found to also sometimes cause depression. So have oral contraceptives, high blood pressure drugs and even statins that treat high cholesterol. [4]

Deficiencies of the nutrients noted in Figure 3 have been associated with depression.

Selenium: An integral part of regulatory proteins (selenoproteins) in the brain; supplementation trials are promising; may alleviate postpartum depression. [5]

Chromium: Elevates serotonin (feel-good neurotransmitter) levels in the brain; may be particularly effective on eating symptoms of depression such as carbohydrate craving and increased appetite, due to its effect on blood sugar regulation. [6]

Folate: Building block for many “feel-good” neurotransmitters such as serotonin, dopamine and norepinephrine; low folate causes poor response to antidepressant meds; the lower the folate, the more severe the depression. [7]

Vitamin B12: Depression may be a manifestation of B12 deficiency; repletion of B12 to adequate levels can improve treatment response; B12 deficiency common in psychiatric disorders. [8]

Vitamin B6: Cofactor for serotonin and dopamine production (feel-good chemicals); studies indicate that low levels may predispose people to depression. [9]

Vitamin B2: Low B2 has been implicated in depression due to its role in methylation reactions in the brain. [10]

Vitamin D: Clinical trials suggest increasing blood levels of vitamin D, which is actually a hormone precursor, may improve symptoms of depression. [11]

Carnitine: Increases serotonin and noradrenaline, which lift mood; in trials, carnitine alleviates depression with few, if any, side effects. [12]

Inositol: Influences signaling pathways in the brain; particularly effective in SSRI (selective serotonin reuptake inhibitor) sensitive disorders. [13]

Biotin: Part of the B-vitamin complex, biotin deficiency has induced depression in animal and human studies. [14]

Antioxidants: Oxidative stress in the brain alters neurotransmitter function; antioxidants protect our brain, which is very sensitive to oxidation; several antioxidants – Vitamins A, C and E, Lipoic Acid, CoQ10, Glutathione and Cysteine – play a key role in prevention and treatment of depression. [15]

Serine: Regulates brain chemistry; involved in NMDA receptor function; acts as a neurotransmitter; low levels correlate with severity of depression. [16]

Zinc: Improves efficiency of antidepressant drugs; particularly useful for treatment resistant patients; regulates neurotransmitters. [17]

Magnesium: Deficiency damages NMDA (N-methyl-D-aspartate) receptors in the brain, which regulate mood; well-documented anti-depressant effects. [18]

An evaluation of someone complaining of depression should include an extensive past medical and surgical history, medication history, family history, and history of any past traumatic events.

Bloodwork should include a CBC, CMP, complete thyroid profile with TSH, Free T4, Free T3, reverse T3, ferritin, TPO and Thyroglobulin antibodies. In addition, fasting insulin; Hgb A1c; salivary hormone testing; food allergy panel; neurotransmitter testing; stool test if indicated to evaluate for abnormal bacteria, yeast, parasites, absorption and digestion; micronutrient analysis through SpectraCell, and neurotransmitter test through Sanesco should also be part of the evalution. (See link for advanced testing. Doug Website)

Therapy

The type of therapy will depend on the results of the individual testing.

Possible therapies: Correcting metabolic dysfunctions (thyroid, insulin), balancing hormones, replacing deficient micronutrients and minerals, repairing abnormal bowel findings, and returning neurotransmitters to balance.

Psychotherapy

Cognitive Behavioral Therapy (CBT)

Self-Help or Support Groups

Stress-Management Techniques

Medication

Anti-Depressant Medications

Recommended Supplements for Depression:

Resources

1. https://www.nimh.nih.gov/health/topics/depression/index.shtml
2. https://www.nimh.nih.gov/health/topics/depression/index.shtml
3. https://www.nimh.nih.gov/health/topics/depression/index.shtml
4. http://www.webmd.com/depression/guide/medicines-cause-depression
5. J Matern Fetal Neonatal Med 2011;24:104-108. Biol Psychiatry 1991;29:1092-1098.
6. Pychopharmacology 2002;159:432-436. J Psychiatr Pract 2005;11:302-314. Biol Psychiatry 2003;53:261-264.
7. J Affect Disord 2000;60:121-130 Altern Med Rev 2008;13:216-226. J Clin Psychiatry 2004;65:1090-1095. Psychiatry Res 1994;53:313-322.
8. Psychiatry 2010;7:42-44 BMC Psychiatry 2003:3:17.
9. J Am Coll Nutr 2008;27:421-427. Fam Pract 2005;22:532-537 Psychother Psychosom 2004;73:340-343.
10. J Affect Disord 2006;96:133-138 Acta Psychiatr Scand 1992;85:360-363.
11. J Intern Med 2008;264:599-609. Acta Paediatr 2012;101:779-783. Med Hypotheses 2007;69:1316-1319
12. Neurochem Int 2012;61:100-107. Drugs Exp Clin Res 1990;16:101-106.
13. Am J Psychiatry 1995;152:792-794. Metab Brain Dis2004;19:51-70.
14. J Parenter Enteral Nutr 1983;7:181-183. Int J Vitam Nutr Res 2004;74:334-340.
15. Biol Psychiatry 2005;58:679-685. NeuroEndocrinol Lett 2009;30:462-469. J Psychosom Res 2004;56:53-58.
16. Curr Opin Neurol 2004;17:197-204 Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1155-1158.
17. Curr Opin Clin Nutr Metab Care 2010;13:685-689. Pol J Pharmacol 2003;55:1143-1147. Psychiatry 1997;42:349-358. Nutr Rev 2006;64:39-42.
18. Magnes Res 2009;22:163S-166S. Med Hypotheses 2010;74:649-660. Pharmacol Rep 2008;60:588-589. Med Hypotheses 2006;67:362-70.