Description

• A primary mood disorder characterized by a depressed mood and/or decreased interest in things that used to give pleasure (anhedonia), which represents a change from previous functioning
• Synonym(s): Unipolar affective disorder, Major depressive disorder
• System(s) affected: Nervous

Epidemiology

Incidence
Affects >18 million in the US

• 13–16% lifetime risk of having major depressive disorder (MDD)
• Recurrence in 50–80% of cases, usually within 2–3 years; risk increases by 16% with each episode

Risk Factors

• Female > Male (2:1)
• Elderly (≥65), although 1st onset usually in 20s
• 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

Genetics
Multiple gene loci place a person at increased risk when faced with environmental stressor; twin studies suggest 37% concordance (1)

Pathophysiology

Complex etiology with 2 major models in the literature (1):

• 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, acetlycholine, 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

Etiology

• Impaired synthesis/metabolism of neurotransmitters
• Environmental factors and learned behavior may affect neurotransmitters and/or have an independent influence on depression.

Commonly Associated Conditions

• Bipolar disorder, cyclothymic disorder, grief reaction, anxiety disorders, schizophrenia/schizoaffective disorders
• Medical comorbidity
• Substance abuse