Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications.
Madeleine Nussbaumer, Paul C Guest, Kolja Schiltz et al.
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In 30 seconds
This systematic review examined immune dysregulation in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) through microglial and kynurenine pathway alterations. MDD exhibited the most consistent in vivo signals with increased TSPO binding in frontolimbic regions, showing lower heterogeneity compared to SCZ. The findings suggest that microglial changes are better understood through biological subgroups rather than categorical diagnoses.
Key findings
- MDD showed increased TSPO binding in frontolimbic regions, indicating immune dysregulation.
- SCZ exhibited heterogeneous TSPO-PET findings with small decreases or no change.
- Postmortem studies indicated either activation-marker increases or loss of homeostatic microglial signatures in SCZ.
- BD evidence was limited, with only one TSPO-PET study reporting hippocampal increases.
Why it matters
Understanding the immune mechanisms underlying affective and psychotic disorders can inform future research and therapeutic strategies. This review highlights the importance of considering biological subgroups and symptom dimensions in psychiatric research.
What to keep in mind
The review notes limited cellular specificity of TSPO-PET, small sample sizes, and a focus on few cortical/limbic regions in postmortem studies.