Major depressive disorder causes

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Major Depressive Disorder (Patient Information)


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Differentiating Major depressive disorder from other Diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [3] Mitra Chitsazan, M.D.[4]


Current theories regarding the causes of major depressive disorder can be broadly classified into two categories, Physiological and Sociopsychological.


Current theories regarding the causes of major depressive disorder can be broadly classified into two categories, Physiological and Sociopsychological.

A. Physiological

Genetic Predisposition

The tendency to develop depression may be inherited: according to the National Institute of Mental Health[1] there is some evidence that depression may run in families. Most experts believe that both biological and psychological factors play a role.


Many modern antidepressant drugs change levels of certain neurotransmitters, namely serotonin and norepinephrine (noradrenaline). However, the relationship between serotonin, SSRIs, and depression is typically greatly oversimplified when presented to the public, though this may be due to the lack of scientific knowledge regarding the mechanisms of action.[2] Evidence has shown the involvement of neurogenesis in depression, though the role is not exactly known. Recent research has suggested that there may be a link between depression and neurogenesis of the hippocampus.[3] This horseshoe-shaped structure is a center for both mood and memory. Loss of neurons in the hippocampus is found in depression and correlates with impaired memory and dysthymic mood. The most widely accepted explanation for this is that the drugs increase serotonin levels in the brain which in turn stimulate neurogenesis and therefore increase the total mass of the hippocampus and would in theory restore mood and memory, therefore assisting in the fight against the mood disorder.

In about one-third of individuals diagnosed with attention-deficit hyperactivity disorder (ADHD), a disorder widely believed to be neurological and developmental, depression is recognized as comorbid.[4] Dysthymia, a form of chronic, low-level depression, is particularly common in adults with undiagnosed ADHD who have encountered years of frustrating ADHD-related problems with education, employment, and interpersonal relationships.[5]

New evidence shows that individuals with clinical depression exhibit markedly higher levels of monoamine oxidase A (MAO-A) in the brain compared to people without depression.[6] MAO-A is an enzyme which reacts with and decreases the concentration of monoamines such as serotonin, norephinephrine and dopamine.

Medical Conditions

Certain illnesses, including cardiovascular disease,[7] hepatitis, mononucleosis, hypothyroidism, fructose malabsorption,[8] sleep apnea, and organic brain damage caused by degenerative conditions such as Parkinson disease, Multiple Sclerosis or by traumatic blunt force injury may contribute to depression, as may certain prescription drugs such as hormonal contraception methods and steroids. Depression also occurs in patients with chronic pain, such as chronic back pain, much more frequently than in the general population. Fibromyalgia Syndrome sufferers also experience depression and anxiety. Dampness or mold in the home is associated with depression,[9] as is the frequent use of aerosols and air fresheners in the home.[10]


Poor diet has been linked with depression. An imbalanced diet or a diet that does not provide enough calories can worsen or induce depression.

Excessive consumption of sugar has been proven to alter mood (causing a 'rush' or 'high', hyperactivity and subsequent deterioration of mood for exapmple, iritability), such consumption can be detrimental regarding the mood changes experienced in depressive conditions. Alcoholic beverages contain the psychoactive drug ethanol, a depressant; If included to a diet in large quantities, it can induce depression. If it is introduced into the diet of a person who is already a depressive, comparatively little can greatly worsen depression both in the short and longer term.[11]

Sleep Quality

Poor sleep quality co-occurs with major depression. Major depression leads to alterations in the function of the hypothalamus and pituitary causing excessive release of cortisol which can lead to poor sleep quality. Individuals suffering from major depression have been found to have an abnormal sleep architecture, often entering REM sleep sooner than usual, along with highly emotionally-charged dreaming. Antidepressant drugs, which often function as REM sleep suppressants, may serve to dampen abnormal REM activity and thus allow for a more restorative sleep to occur.

Seasonal Affective Disorder

Seasonal affective disorder (SAD) is a type of depressive disorder that occurs in the winter when daylight hours are short. It is believed that the body's production of melatonin, which is produced at higher levels in the dark, plays a major part in the onset of SAD and that many sufferers respond well to bright light therapy, also known as phototherapy.[12]

Postpartum Depression

Postpartum depression refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression, which has incidence rate of 10-15%, typically sets in within three months of labor, and can last for as long as three months.[13] About two new mothers out of 1000 experience Postnatal Psychosis, which includes hallucinations and/or delusions.

B. Sociological

Psychological Factors

Low self-esteem and self-defeating or distorted thinking are connected with depression. However, it has been proposed that it is the result of depression and not necessarily the cause of it. This is still debated in the scientific community. Although it is not clear which is the cause and which is the effect, it is known that depressed persons who are able to make corrections in their thinking patterns can show improved mood and self-esteem (Cognitive Behavioral Therapy).[14] Psychological factors related to depression include the complex development of one's personality and how one has learned to cope with external environmental factors, such as stress.[15]

Early Experiences

Events such as the death of a parent, issues with biological development, school related problems, abandonment or rejection, neglect, chronic illness, and physical, psychological, or sexual abuse can also increase the likelihood of depression later in life. Post-traumatic stress disorder (PTSD) includes depression as one of its major symptoms.[16]

Life Experiences

The following experiences or circumstances may trigger depression:


  1. Genetic Link Found for Depression
  2. PLME0212_1211-1216.indd
  3. Dr Helen Mayberg, quoted in Scientific American, volume 17, number 4, pp. 26-31
  4. Hallowell, Edward M.; John J. Ratey (2005). Delivered from Distraction : Getting the Most out of Life with Attention Deficit Disorder. New York: Ballantine Books, p. 253–5. ISBN 0-345-44231-8.
  5. see Hallowell and Ratey, 2005
  6. Jeffrey H. Meyer, MD, PhD; Nathalie Ginovart, PhD; Anahita Boovariwala, BSc; Sandra Sagrati, BSc; Doug Hussey, BSc; Armando Garcia, BSc; Trevor Young, MD, PhD; Nicole Praschak-Rieder, MD; Alan A. Wilson, PhD; Sylvain Houle, MD, PhD, "Elevated Monoamine Oxidase A Levels in the Brain -- An Explanation for the Monoamine Imbalance of Major Depression," Arch Gen Psychiatry. 2006;63:1209-1216.[1]
  7. Manev, R (2004). "5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders". Critical Reviews in Neurobiology. 16 (1?2): 181?6. Unknown parameter |coauthors= ignored (help)
  8. Ledochowski M, Sperner-Unterweger B, Widner B, Fuchs D (1998). "Fructose malabsorption is associated with early signs of mental depression". Eur. J. Med. Res. 3 (6): 295–8. PMID 9620891.
  9. Dampness and Mold in the Home and Depression: An Examination of Mold-Related Illness and Perceived Control of One’s Home as Possible Depression Pathways Edmond D. Shenassa, ScD, Constantine Daskalakis, ScD, Allison Liebhaber, BA, Matthias Braubach, MPH and MaryJean Brown, ScD, RN October 2007, Vol 97, No. 10 | RESEARCH AND PRACTICE | American Journal of Public Health 1893-1899 © 2007 American Public Health Association DOI: 10.2105/AJPH.2006.093773 PMID 17761567
  10. "Symptoms of mothers and infants related to total volatile organic compounds in household products" Arch Environ Health. 2003 Oct;58(10):633-41; PMID 15562635; "Air fresheners can make mothers and babies ill" University of Bristol press release issued 19 October 2004
  13. eMedicine - Postpartum Depression : Article by Ruta M Nonacs
  17. NJC Andreasen (1972), "The role of religion in depression", Journal of Religion and Health, Springer