ArticleResearch square2026
Differential brain neuroimmune profiles and altered immune balance in autism spectrum disorder compared with psychotic disorder and neurotypical controls.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Alterations in immune and neuroinflammatory processes are evident in neurodevelopmental disorders, including autism (ASD) and psychotic disorders. While prior studies using cerebral spinal fluid and serum have identified differences in cytokine levels in ASD or psychotic disorders when compared with controls, specific changes in postmortem human brain tissue remains poorly characterized, making cross-disorder comparisons uncertain. The superior temporal gyrus (STG), involved in social communication and sensory processing, is affected in both conditions, making it a relevant region for investigating immune-related differences. This study aimed to compare neuroimmune profiles in ASD and psychotic disorders. STG tissue was analyzed from 72 postmortem cases: ASD (n = 17), psychotic disorders (n = 26), and neurotypical controls (n = 29). Fresh-frozen samples were collected using biopsy punches, and cytokines, chemokines, and growth factors were quantified using multiplexed bead immunoassays. In ASD cases, there were significantly increased levels of inflammatory cytokines IL-1α, IL-8, G-CSF, M-CSF and GROa compared to both controls and psychotic disorder. In contrast, there was a significant decrease in IFNα2 and IL-4 cytokine levels in ASD compared to both controls and psychotic disorders. In the psychotic disorder group, there were increases in inflammatory chemokines eotaxin, fractalkine and RANTES compared to ASD and controls. Notably, there was a concomitant rise in regulatory cytokines TGFβ1 and IL-10 in psychotic disorder suggestive of compensatory response that was not observed in ASD. Overall, ASD presented a distinctive STG cytokine profile with an increased pro-inflammatory cytokine levels and reduced immune regulatory balance, whereas psychotic disorder exhibited significant variations in chemokines and growth factors but incorporating greater immune regulation. These data highlights that unique neuroimmune pathways occur in different neurodevelopmental disorders offering insights into potential therapeutic targets tailored to each condition.
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