Biological aspects of drug resistance in schizophrenia

In order to systematize the current data of Russian and international literature on the biological aspects of the development of therapeutically resistant schizophrenia (TRS), the literature sources in the MEDLINE/PubMed, Scopus, Elibrary, Google Scholar, and Cyberleninka databases from 2009 to 2024, as well as relevant papers in the references of the analyzed publications were selected, reviewed, and systematized by the keywords «therapeutically resistant schizophrenia», «dopamine supersensitivity psychosis», «biological predictors of the development of resistance in schizophrenia», «neuroinflammation and drug resistance». Modern studies reveal distinct biological differences between patients with schizophrenia responding to antipsychotic therapy and those resistant to it. Biological hypotheses for the development of TRS are based either on the dysfunction of neurotransmitter pathways (impaired dopamine sensitivity, dysfunction of the glutamatergic and GABAergic systems) or on systemic pathological processes. These models are not mutually exclusive: each may contribute to drug resistance in schizophrenia. Understanding the underlying pathophysiology of TRS can aid in selecting a treatment approach and developing future therapies.