Markers of neuroinflammation in the CSF of patients with difficult to treat psychiatric disease

Introduction The immune system is recognized as participating in the pathophysiology of psychiatric disease and there is renewed interest in identifying biomarkers of this immune activation. Methods We measured serum and cerebral spinal fluid (CSF) autoantibodies with other routine and novel markers of neuroinflammation, including CSF cytokines in patients with atypical psychiatric presentations of both psychotic and mood disorders (n=35). Their markers were compared with cohorts of non-inflammatory neurological disease (NIND) controls (n=18), patients with central nervous system (CNS) viral infection (n=22) and autoimmune encephalitis (AE; n=40). Results The most common autoantibody detected in the serum of patients with psychiatric disease were anti-nuclear antibodies followed by thyroid autoantibodies. Few atypical psychiatric patients had abnormal conventional CSF markers of neuroinflammation (pleocytosis, oligoclonal bands, abnormal CSF IgG: albumin ratio). Further analysis of CSF revealed elevation of ITAC/CXCL11 in the psychiatric cohort. TARC/CCL17 was lower in the psychiatric cohort compared to other groups in a random-effects multinomial model, despite no significant differences on univariate analysis. When the values of CSF cytokines were examined in individual patients, six patients (17%) had at least one CSF cytokine greater than four standard deviations above the mean of the NIND cohort group. Extensive serological evaluation revised the diagnoses of six (17%) of our psychiatric group, and these patients’ showed improvement with immunosuppression. Conclusion Our results suggest a subset of people with atypical psychiatric disease may have a predominant immune contribution. This highlights the need for reevaluation and further consideration of differential diagnosis where patient presentations are not clinically typical, do not respond to conventional psychotropic treatment, or if other risk factors for autoimmunity are present.