The neurotransmitter hypothesis of depression most supported by current evidence implicates deficiency of which monoamine(s), with serotonin being central?
- A Dopamine excess in the mesolimbic pathway
- B Serotonin and norepinephrine deficiency (monoamine hypothesis) ✓
- C GABA deficiency exclusively
- D Acetylcholine excess in the limbic system
Correct answer: B. Serotonin and norepinephrine deficiency (monoamine hypothesis)
Explanation
The monoamine hypothesis of depression proposes functional deficiency of serotonin (5-HT) and norepinephrine (NE) in limbic-cortical circuits. This underpins SSRI, SNRI, TCA, and MAOI mechanisms. Current evidence also implicates neuroplasticity (reduced BDNF, hippocampal atrophy) and HPA axis hyperactivity. Dopamine excess is central to the dopamine hypothesis of schizophrenia. GABA deficiency is more relevant to anxiety disorders. Cholinergic excess plays a role but is not the primary monoamine hypothesis.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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