Depression, bipolar disorder and schizophrenia are classically considered separate diseases. Biologically, however, they overlap significantly. A new systematic review by the Department of Psychiatry and Psychotherapy Magdeburg suggests that inflammatory processes and changes in the kynurenine metabolic pathway play a role in all three disorders – and more so in biological subgroups than in classical diagnostic limits.

The research team led by Prof. Johann Steiner analysed data from three different levels: TSPO-PET imaging (immune activity in the living brain), cerebrospinal fluid (kynurenine metabolites) and post-mortem brain tissue analyses (microglia and enzymes). The results do not show a uniform pattern, but differentiated changes depending on the disease, brain region and method.

The findings were most consistent in major depressive disorder: There was increased immune activity in brain regions that are relevant for mood, stress processing and emotion regulation. In schizophrenia, imaging results were inconsistent, while cerebrospinal fluid and tissue analyses indicated a shift in kynurenine metabolism that could interfere with neuronal signaling. For bipolar disorder, the data was even sparse, with evidence of changes in certain subgroups (e.g., psychotic symptoms or suicidality).

The central finding of the study is that microglial and kynurenine changes can be better explained by biological subgroups and concrete symptoms than by rigid diagnostic limits. In the long term, this could lead to a more precise, dimensional and biologically oriented psychiatry.

First author Madeleine Nussbaumer, who is writing her doctoral thesis in Prof. Steiner’s research group, emphasized that the findings from the different methods only complement each other when viewed together to form a coherent picture.

The study has been published in the journal Molecular Psychiatry . It builds on earlier work by the Magdeburg group, which had described schizophrenia as a “glial” disease. The researchers see this as a step towards personalized psychiatry that takes greater account of biological mechanisms. However, further studies with larger cohorts and long-term courses are necessary.

Original publications:

Nussbaumer, M., Guest, P.C., Schiltz, K. et al. Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications. Mol Psychiatry (2026). DOI: https://doi.org/10.1038/s41380-026-03614-3

Bernstein, H.-G., Nussbaumer, M., Vasilevska, V., Dobrowolny, H., Nickl-Jockschat, T., Guest, P.C., Steiner, J. Glial cell deficits are a key feature of schizophrenia: implications for neuronal circuit maintenance and histological differentiation from classical neurodegeneration. Mol Psychiatry 30, 1102–1116 (2025). DOI: https://doi.org/10.1038/s41380-024-02861-6

Editor: X-Press Journalistenbüro GbR

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