Immune Cell Profiles Offer Insights Into Schizophrenia Treatment Resistance: Study

New Delhi: Could immune system changes explain why some schizophrenia patients respond to treatment while others don’t?

A recent study by researchers from Singapore's Institute of Mental Health and Singapore Immunology Network has revealed how immune system changes may influence schizophrenia and treatment responses.

The study, published in Brain, Behaviour, and Immunity, investigates the role of immune cell populations in explaining why some patients respond to antipsychotic medications while others remain resistant.

"Immune dysfunction has been linked to psychosis for years. Our findings show significant differences in immune cell populations among schizophrenia patients, particularly those with treatment resistance," said Dr. Jimmy Lee, the study’s corresponding author.

The research examined 196 participants, including 147 schizophrenia patients categorized into antipsychotic-responsive (ARS), clozapine-responsive (nCR-TRS), and clozapine-resistant (CR-TRS) groups, alongside 49 healthy controls. Using advanced immunophenotyping, the researchers analysed 66 immune cell subtypes to identify distinct patterns associated with schizophrenia and its varying responses to treatment.

The findings revealed a reduction in key immune populations, including mucosal-associated invariant T (MAIT) cells, plasmablasts, and IgG+ B cells, in schizophrenia patients. "MAIT cells, particularly their CD8+ and double-negative subsets, showed a strong association with increasing treatment resistance. This highlights their potential as biomarkers for schizophrenia subtypes," noted Dr. Yanhui Li, the study’s lead author.

Conversely, an increase in naïve CD4+ T cells and CCR5+/CCR2+ myeloid cells was observed in treatment-resistant patients. These findings suggest that immune mechanisms may play a role in driving treatment resistance, opening up possibilities for new therapeutic approaches targeting these pathways.

The study also highlighted the CD4/CD8 ratio as a promising biomarker, showing a consistent increase in patients with greater treatment resistance. This discovery could help identify individuals at risk for treatment-resistant schizophrenia (TRS). "The CD4/CD8 ratio has emerged as a potential immune biomarker for antipsychotic response and resistance in schizophrenia," the authors concluded.

The research underscores the importance of integrating immune-based studies into psychiatric care. "Understanding the immune profiles of schizophrenia patients can guide precision treatments and improve outcomes," Dr. Lee added.

By revealing the immune system's role in treatment resistance, this study paves the way for improved management of schizophrenia and emphasizes the need for further exploration of immune-targeted therapies.