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

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  • A primary mood disorder characterized by a sustained depressed mood and/or decreased interest in things that used to give pleasure (anhedonia), which represents a change from previous functioning.
  • Variants: (1) major depressive disorder (MDD), (2) dysthymic disorder, and (3) depressive disorder not otherwise specified (NOS). (Last two disorders have slightly different diagnostic criteria but are still treated as below.)


In United States, 6.9% of 18 years of age or older in past year

  • 16.2% lifetime risk of having MDD
  • Patients can relapse; risk decreases with longer remission period but increases in patients with severe episodes, episodes at a younger age, and multiple episodes.
  • Predominant age
    • Low risk before early teens but highest prevalence in teens and young adults
  • Predominant gender
    • Females > males (2:1)

Etiology and Pathophysiology

Complex etiology with two major models in the literature

  • 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.
  • Other areas of research interest: inflammatory processes and 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 (1).

Risk Factors

  • Female > male (2:1)
  • Severity of 1st 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
  • 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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