Depression is a topic covered in the 5-Minute Clinical Consult.

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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
    • Females > males (2:1)

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).

Risk Factors

  • 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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