Clinical depression pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

The exact pathogenesis of major depressive disorder is not fully understood. However, it is thought that major depressive disorder is the result of decreased levels of serotonin, norepinephrine, and dopamine.

Pathophysiology

• The exact pathogenesis of major depressive disorder is not completely understood; however, following etiologies have been suggested to play a role in the development of major depressive disorder.
  • 1. Neurotransmitters
    • Serotonin: Serotonin depletion has been most commonly shown to be associated with depression. For this reason, serotonergic agents are first-line treatment of major clinical depression.
    • Norepinephrine: Abnormal norepinephrine metablites have been shown in blood, urine, and CSF in patients with major depressive disorder. Serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine) increase both serotonin and norepinephrine levels and are used as the firs-line treatment of major depressive disorder.
    • Dopamine: major depressive disorder may be associated with decreased dopaminergic activity. It has been suggested that patients with major depressive disorder may have dysfunctional [masolimbic dopamine pathway]] and/or hypoactive dopamine D1 receptors. Reduced dopamine concentrations with drugs (e.g. reserpine) or certain pathologic conditions (e.g. Parkinson's disease) have been linked to symptoms of depression. In addition, drus increasing dopamine concentrations, such as amphetamine, bupropion, and tyrosine can reduce depressive symptoms.
  • 2. Psychosocial
  • 3. Cognitive: Cognitive theory of Aaron Beck describes a triad of 1) negative self-view 2) negative interpretation of experience and 3) negative view of future
  • 4. Learned helplessness: Based on this theory, depression is linked to an individual's inability to control events.
  • 5. Stressful life events: Stressful life events may result in permanent neuronal alterations, subsequently predisposing an individual to mood disorders. The most often associated life event linked to development of depression is losing a parent before age 11.

Genetics

[Disease name] is transmitted in [mode of genetic transmission] pattern.

OR

Genes involved in the pathogenesis of [disease name] include:

• [Gene1]
• [Gene2]
• [Gene3]

OR

The development of [disease name] is the result of multiple genetic mutations such as:

• [Mutation 1]
• [Mutation 2]
• [Mutation 3]

Associated Conditions

Conditions associated with [disease name] include:

• [Condition 1]
• [Condition 2]
• [Condition 3]

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Image

Brain chemicals called neurotransmitters allow electrical signals to move from the axon of one nerve cell to the neuron of another. A shortage of neurotransmitters impairs brain communication.

References