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- A primary mood disorder characterized by a sustained feeling of sadness and/or decreased interest in all or most activities once enjoyed (anhedonia), which represents a change from previous functioning
- Variants: disruptive mood dysregulation disorder, major depressive disorder (MDD), persistent depressive disorder (dysthymia), premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, other specified depressive disorder, unspecified depressive disorder
In United States, 8.1% of adults aged ≥20 years experienced depression in a given 2-week period between 2013 and 2016 (1).
- 19.2% lifetime risk of having MDD (2)
- Patients can relapse; risk decreases with longer remission periods but increases with severe or multiple episodes and episodes at a younger age.
- Predominant age
- Low risk before early teens but highest prevalence in teens and young adults
- Predominant gender
Etiology and Pathophysiology
There are diverse theories on the pathophysiology of depression.
- Monoamine-deficiency hypothesis: symptoms related to decreased levels of norepinephrine (dullness and lethargy) and serotonin (irritability, hostility, and suicidal ideation) in multiple regions of the brain; other neurotransmitters involved include dopamine, acetylcholine, γ-aminobutyric acid (GABA), glutamate.
- Stress/hypothalamic–pituitary–adrenal axis: Abnormalities in cortisol response lead to depression; elevated cortisol levels can be associated with depression, but cortisol tests are not indicated for diagnosis.
- Depression as inflammatory disorder: Proinflammatory marker levels are reported to be elevated in depressed patients. Examples of these markers are C-reactive protein (CRP), interleukin (IL)-6, IL-1, and tumor necrosis factor-α (TNF-α).
- Hormones and depression: Reduction in thyroid hormone, estrogen levels, and elevation in vasopressin has been seen in people with depression.
- Other areas of research interest: abnormal circadian rhythms; impaired synthesis/metabolism of neurotransmitters
- Environmental factors and learned behavior may affect neurotransmitters and/or have an independent influence on depression.
Multiple gene loci place a person at increased risk when faced with environmental stressor; twin studies suggest 37% concordance (3).
- Female > male (2:1)
- Severity of first episode
- Persistent sleep disturbances
- Presence of chronic disease(s), recent myocardial infarction (MI), cardiovascular accident (CVA)
- Strong family history (depression, bipolar, suicide, substance abuse), spouse with depression
- Childhood trauma/maltreatment
- Substance abuse and dependence, domestic abuse/violence
- Losses, stressors, unemployment
- Single, divorced, or unhappily married
Commonly Associated Conditions
- Bipolar disorder, cyclothymic disorder, grief reaction, anxiety disorders, somatoform disorders, schizophrenia/schizoaffective disorders
- Medical comorbidity
- Substance abuse
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