Clinical meaning
Schizophrenia is a chronic psychotic disorder affecting approximately 1% of the population worldwide, characterized by positive symptoms (hallucinations, delusions, disorganized speech, disorganized behavior), negative symptoms (flat affect, alogia, avolition, anhedonia, social withdrawal), and cognitive deficits (impaired working memory, executive function, attention). The dopamine hypothesis remains central: hyperactivity of mesolimbic dopamine pathways (ventral tegmental area → nucleus accumbens) drives positive symptoms, while hypoactivity of mesocortical dopamine pathways (VTA → prefrontal cortex) drives negative and cognitive symptoms. All effective antipsychotics block D2 dopamine receptors in the mesolimbic pathway. However, D2 blockade in the nigrostriatal pathway causes extrapyramidal symptoms (EPS) and in the tuberoinfundibular pathway causes hyperprolactinemia. The glutamate (NMDA) hypofunction hypothesis, supported by the fact that NMDA antagonists (PCP, ketamine) produce symptoms mimicking both positive and negative symptoms of schizophrenia, may explain the full spectrum of the disease. Serotonin-dopamine interactions are exploited by second-generation (atypical) antipsychotics, which block both 5-HT2A and D2 receptors — the 5-HT2A blockade reduces nigrostriatal D2 blockade, resulting in lower EPS risk while maintaining antipsychotic efficacy. The NP must understand that schizophrenia is a chronic illness requiring lifelong antipsychotic therapy; non-adherence is the leading cause of relapse.