Neurobiologically, the mesocortical dopamine pathway projecting to the prefrontal cortex is HYPOACTIVE in schizophrenia. Which symptom cluster does this most directly explain?

• A Positive symptoms (hallucinations, delusions)
• B Tardive dyskinesia
• C Extrapyramidal side effects of antipsychotics
• D Negative symptoms (blunted affect, alogia, avolition) ✓

Explanation

The dopamine hypothesis of schizophrenia involves multiple pathways. The mesolimbic pathway (VTA to nucleus accumbens) is HYPERACTIVE, mediating positive symptoms (hallucinations, delusions). The mesocortical pathway (VTA to prefrontal cortex) is HYPOACTIVE, mediating negative and cognitive symptoms (alogia, avolition, working memory deficits). Tardive dyskinesia arises from nigrostriatal dopamine receptor upregulation after chronic blockade. EPS (acute) arises from D2 blockade in the nigrostriatal pathway. Understanding pathway-specific effects predicts why D2 blockade treats positive symptoms but can worsen negative symptoms.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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