Which of the following neurotransmitter systems is primarily implicated in the pathophysiology of Major Depressive Disorder according to the monoamine hypothesis?

Explanation

## The Monoamine Hypothesis of Major Depressive Disorder **Key Point:** The monoamine hypothesis posits that depression results from a **deficiency of serotonin (5-HT), norepinephrine (NE), and dopamine (DA)** in key brain regions. This is the foundational neurochemical model underlying modern antidepressant therapy. ### The Three Key Monoamines | Neurotransmitter | Brain Region | Function in Depression | | --- | --- | --- | | **Serotonin (5-HT)** | Prefrontal cortex, limbic system | Mood regulation, anxiety, sleep | | **Norepinephrine (NE)** | Locus coeruleus, prefrontal cortex | Attention, arousal, motivation | | **Dopamine (DA)** | Ventral tegmental area, nucleus accumbens | Reward, motivation, pleasure | ### Evidence Supporting the Monoamine Hypothesis 1. **SSRIs** (selective serotonin reuptake inhibitors) increase synaptic serotonin → antidepressant effect 2. **SNRIs** (serotonin-norepinephrine reuptake inhibitors) target both 5-HT and NE 3. **Tricyclic antidepressants** block reuptake of all three monoamines 4. **Reserpine** (depletes monoamines) induces depression 5. **Monoamine oxidase inhibitors** (MAOIs) prevent degradation of monoamines → antidepressant effect **High-Yield:** The monoamine hypothesis is the basis for 90% of antidepressant drug design and is heavily tested in NEET PG. Know the three monoamines and their roles. **Clinical Pearl:** While the monoamine hypothesis is clinically useful and explains drug action, newer models (neuroplasticity, inflammation, HPA axis dysregulation) suggest the full picture is more complex. However, for board exams, monoamine deficiency remains the primary teaching model. **Mnemonic:** **SND = Sad, No Drive** — **S**erotonin (mood), **N**orepinephrine (drive/attention), **D**opamine (dopamine/pleasure).