Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression

Abstract

Introduction: Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders.

Methods: Articles were identified by searching Pub Med, PsycInfo, and Web of Science, and the reference lists of these studies.

Results: Twenty-eight studies met the inclusion criteria (16 schizophrenia, 4 bipolar disorder, and 9 MDD). CSF levels of IL-1β and kynurenic acid were significantly increased in patients with schizophrenia and bipolar disorder compared to healthy controls (P < .001). CSF levels of IL-6 and IL-8 were significantly increased in patients with schizophrenia and MDD compared to healthy controls (P ≤ .013).

Discussion: There is preliminary evidence for similarities in the pattern of CSF cytokine and tryptophan catabolite alterations across major psychiatric disorders, although findings must be interpreted with caution in light of small numbers of studies/subjects. Many CSF alterations are also concordant with those in the peripheral blood, particularly for schizophrenia. Findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.

Keywords: bipolar disorder; cerebrospinal fluid; cytokines; inflammation; major depressive disorder; meta-analysis; schizophrenia.

Fig. 1.

Cerebrospinal fluid (CSF) cytokine and tryptophan catabolite alterations in patients with schizophrenia, bipolar disorder, and major depressive disorder vs controls.

Fig. 2.

Forest plots of cerebrospinal fluid (CSF) IL-6 alterations in patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD) vs controls. (a) Schizophrenia, (b) bipolar disorder, and (c) MDD.