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Tikhonov D.V.

Mental Health Research Centre

Kaleda V.G.

Mental Health Research Centre

Biological aspects of drug resistance in schizophrenia

Authors:

Tikhonov D.V., Kaleda V.G.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(1): 19‑25

DOI: 10.17116/jnevro202612601119

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Table of contents

BIOLOGICAL ASPECTS OF DRUG RESISTANCE IN SCHIZOPHRENIA
BIOLOGICAL ASPECTS OF DRUG RESISTANCE IN SCHIZOPHRENIA

To cite this article:

Tikhonov DV, Kaleda VG. Biological aspects of drug resistance in schizophrenia. S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(1):19‑25. (In Russ.)
https://doi.org/10.17116/jnevro202612601119

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)
МСФ на ЯМ
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Abstract:

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.

Keywords:

therapeutically resistant schizophrenia
dopamine supersensitivity psychosis
hyperdopaminergic and normodopaminergic schizophrenia
NMDA
GABA
neuroinflammation

Authors:

Tikhonov D.V.

Mental Health Research Centre

Kaleda V.G.

Mental Health Research Centre

Received:

21.07.2025

Accepted:

18.09.2025

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