Depressive Disorder - Causes

The exact cause of depressive disorder is unknown. Heredity plays an unclear role; depression is more common among first-degree relatives of a patient with depression, and concordance is high between monozygotic twins. An inherited genetic polymorphism in the activity of the serotonin transporter in the brain may be triggered by stress. People who experienced childhood abuse or other severe stress and who have the short allele of this transporter are twice as likely to develop depression compared to those who have the long allele.

Other theories focus on changes in neurotransmitter levels, including dysregulation of cholinergic, catecholaminergic (norepinephrine and dopaminergic), and serotonergic (5-hydroxytryptamine) neurotransmission. Neuroendocrine dysregulation may also be involved, with particular emphasis on three axes: the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, and growth hormone.

Psychosocial factors also appear to be involved. Significant life stressors, especially separations and losses, often precede episodes of major depression; however, these events do not usually cause prolonged, severe depression, except in people with a predisposition to mood disorders.

Patients who have had a major depressive episode in the past have a significant risk of having subsequent episodes. Introverted people and those with anxious personality traits are more likely to develop depressive disorder. Such people often lack social skills to cope with difficult life situations. Depression can also develop in people with other mental disorders.

Women have a higher risk of developing depression, but there is no theory to explain this. It may be due to greater exposure to or heightened response to daily stress, higher levels of monoamine oxidase (an enzyme that breaks down neurotransmitters important in mood regulation), and endocrine changes associated with the menstrual cycle and menopause. In postpartum depression, symptoms develop within four weeks after delivery; endocrine changes are likely involved, but the specific cause is unknown. Women are also more likely to have thyroid dysfunction.

In seasonal affective disorder, symptoms develop with seasonal periodicity, usually in the fall and winter. The disorder tends to occur in climates with long and severe winters. Depressive symptoms or disorders may be associated with various somatic diseases, including thyroid and adrenal diseases, benign and malignant brain tumors, stroke, AIDS, Parkinson's disease, and multiple sclerosis. Certain medications, such as glucocorticoids, some beta blockers, antipsychotics (especially in the elderly), and reserpine, may lead to the development of depressive disorders. Abuse of certain recreational substances (e.g., alcohol, amphetamines) may lead to the development of concomitant depression. Toxic effects or withdrawal of these drugs may cause transient depressive symptoms.

Some Causes of Depression and Mania Symptoms

Type of disorder	Depression	Mania
Connective tissue	Systemic lupus erythematosus	Rheumatic fever Systemic lupus erythematosus
Endocrine	Addison's disease Cushing's disease Diabetes mellitus Hyperparathyroidism Hyperthyroidism and hypothyroidism Hypopituitarism	Hyperthyroidism
Infectious	AIDS Progressive paralysis (parenchymatous neurosyphilis) Flu Infectious mononucleosis Tuberculosis Viral hepatitis Viral pneumonia	AIDS Progressive paralysis Flu St. Louis Encephalitis
Neoplastic	Cancer of the head of the pancreas Disseminated carcinomatosis
Neurological	Brain tumors Severe epileptic seizures (temporal lobe) Traumatic brain injury Multiple sclerosis Parkinson's disease Sleep apnea Stroke (frontal region left)	Severe epileptic seizures (temporal lobe) Diencephalic tumors Traumatic brain injury Huntington's disease Multiple sclerosis Stroke
Eating disorders	Pellagra Pernicious anemia
Other	IHD Fibromyalgia Renal or hepatic failure
Mental	Alcoholism and other substance use disorders Antisocial personality Early stage dementia disorders Schizophrenic disorders
Pharmacological	Amphetamine Withdrawal Amphotericin B Anticholinesterase insecticides Barbiturates Cimetidine Glucocorticoids Cycloserine Indomethacin Mercury Metoclopramide Phenothiazines Reserpine Thallium Vinblastine Vincristine	Amphetamines Some antidepressants Bromocriptine Cocaine Glucocorticoids Levodopa Methylphenidate Sympathomimetic agents

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