A 48-year-old woman with severe major depressive disorder with melancholic features is being considered for electroconvulsive therapy. She has failed two adequate antidepressant trials. Which neurobiological mechanism best explains the therapeutic efficacy of ECT in severe depression?
- A Downregulation of presynaptic alpha-2 adrenergic receptors in the locus coeruleus
- B Downregulation of hypothalamic-pituitary-adrenal axis hyperactivity and increased brain-derived neurotrophic factor ✓
- C Upregulation of monoamine oxidase A activity in the prefrontal cortex
- D Selective blockade of serotonin 5-HT2A receptors in the raphe nuclei
Correct answer: B. Downregulation of hypothalamic-pituitary-adrenal axis hyperactivity and increased brain-derived neurotrophic factor
Explanation
ECT's therapeutic effect is attributed to normalisation of HPA axis hyperactivity and upregulation of BDNF, promoting neuroplasticity. This is well established in standard psychiatry texts. Option A describes a downstream effect of chronic antidepressant use, not ECT. Option C is incorrect as MAO-A activity is not increased by ECT. Option D describes a mechanism of certain atypical antipsychotics, not ECT.
Reference: Kaplan and Sadock's Comprehensive Textbook of Psychiatry, 11th ed.
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