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

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-1ß 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.

Are leptin levels increased among people with schizophrenia versus controls? A systematic review and comparative meta-analysis.

OBJECTIVE: Leptin may play a role in the pathophysiology of schizophrenia and it remains unclear if levels are raised compared to controls. Therefore, we performed a systematic review and meta-analysis comparing leptin levels among people with schizophrenia and controls. METHOD: Two authors independently searched major electronic databases from inception until June 2015 for studies measuring blood leptin levels among people with schizophrenia and controls. Random effects meta-analysis calculating hedges g and 95% confidence intervals (CI) and meta-regression analyses were conducted. RESULTS: Twenty-seven articles representing 1674 individuals with schizophrenia (34.6 ± 6.8 years, 55% male (0-100%), BMI 25.2 ± 3.1) and 2033 controls (33.9 ± 7.0 years, 51% male (0-100%), BMI=24.1 ± 2.1) were included. Across all studies, leptin levels may be marginally higher in schizophrenia (g=0.164, 95% CI -0.014-0.341, p=0.07, Q=217, p<0.01), particularly when one outlier was removed (g=0.196, 95% CI 0.210-0.370, p=0.02) and when we included the smallest effect size from studies with multiple comparisons (g=0.318, 95% CI 0.125-0.510, p=0.001). Leptin levels were higher in multi-episode schizophrenia (g=0.245, 95% CI 0.058-0.433, p=0.01) and females (g=0.557 95% CI 0.16-0.954, p=0.006). Subgroup analyses revealed leptin levels may be higher in participants taking second-generation antipsychotics compared to controls. Multivariate meta-regression demonstrated a lower percentage of males (ß=-0.0064, 95% CI -0.0129 to -0.0002, p=0.05), but not BMI, moderated the results. CONCLUSION: Our results suggest that schizophrenia is associated with increased blood leptin levels compared to controls, which may not be entirely attributable to antipsychotic medication or BMI. Other illness related and lifestyle choices may play a pivotal role.