Few studies have been conducted examining cytokines in cerebrospinal fluid of patients compared to healthy volunteers. The goals of this study were: 1) to report original data detailing cytokine levels in the cerebrospinal fluid (CSF) of 10 patients with a schizophrenia spectrum disorder (SSD) diagnosis and 10 healthy controls and 2) to conduct a meta-analysis of the available data on cytokine levels in the CSF of patients with SSD compared to healthy controls, including our new data. Cytokine concentrations were measured using the Q-plex Human Cytokine Screen array in CSF of 10 patients with SSD and 10 healthy volunteers. For the meta-analysis, an electronic PubMed and Google Scholar search without restrictions was conducted for articles that reported on cytokine levels in CSF in patients with an SSD compared to healthy controls. Our original data revealed statistically significant increases in levels of interleukin-8 (IL-8) and interleukin-1 beta (IL-1β) in the CSF of patients with an SSD compared to healthy volunteers. Our meta-analysis showed statistically significant increases in interleukin-6 (IL-6) and IL-8 in patients compared to healthy volunteers. Effect sizes between treated and untreated patients for IL-6 were of similar magnitude. However, IL-6 levels were higher in early stage schizophrenia patients compared to chronic schizophrenia patients. Studies with larger sample sizes, comprehensive assessments and ideally in the context of a randomized controlled intervention to minimize the impact of confounding factors are needed to fully understand the role of cytokines and inflammatory markers in the pathophysiology and treatment of schizophrenia.

Abnormalities in the complement system have been described in patients with schizophrenia, with those individuals having greater frequency of complement component 4A (C4A) alleles and higher C4A transcript levels in postmortem brain tissue. Importantly, abnormalities in C4A and other complement molecules have been associated with synaptic pruning abnormalities that occur during neurodevelopment. A few studies have investigated C4 levels in living patients with schizophrenia, but all of them did so using peripheral blood samples. No studies have examined C4 levels in cerebrospinal fluid (CSF), presumably a better biofluid choice given its intimate contact with the brain. Therefore, we report for the first time on C4 levels in CSF and plasma of patients with schizophrenia. In this study, we obtained CSF in 32 patients with schizophrenia spectrum disorders and 32 healthy volunteers and peripheral blood samples in 33 SSD and 31 healthy volunteers. C4 levels were measured using Abcam ELISA assays. Univariate analysis did not show a statistically significant difference in CSF C4 values between groups. However, a multivariable analysis showed a statistically significant increase in CSF C4 levels between groups after adjusting for sex and age. We also observed a high correlation between CSF C4 levels and age. By contrast, plasma C4 levels were not significantly different between groups. CSF and plasma C4 levels were not significantly correlated. Therefore, the use of CSF samples is critical and should be complementary to the use of peripheral blood samples to allow for a comprehensive understanding of complement C4 abnormalities in schizophrenia.

As a whole, the SSD group had higher odds of aggression than the bipolar disorder group. However, after subdividing the groups, schizophrenia had higher odds of aggression than bipolar disorder with a recent manic episode and lower odds of aggression than bipolar disorder with a recent mixed episode.

Objective: To characterize variability in daily life functioning among individuals with serious mental illness based on a naturalistic performance measure of grocery shopping and standard neuropsychological tasks using cluster analytic methods. Methods: A naturalistic performance measure, the Test of Grocery Shopping Skills (TOGSS), and standard neuropsychological tasks, were completed by 191 participants with serious mental illness. Hierarchical cluster analytic techniques were used to explore functional subgroups based on naturalistic performance measure variables. Multivariate analyses of variance were utilized to compare subgroups on TOGSS variables and neuropsychological measures, respectively. Results: Two distinct functional subgroups emerged from the cluster analysis. On average, participants in cluster one were faster, more efficient, and more accurate compared to cluster two. Based on performance on neuropsychological tasks, cluster one had better verbal memory, visual attention, and processing speed, and executive functioning scores, compared to cluster two. The clusters did not differ on a measure of auditory working memory. Conclusions and Implications for Practice: Naturalistic performance measures can assist with characterizing the heterogeneity in real life functioning among people with serious mental illness. Further work to illuminate the relationship between specific cognitive abilities and specific functional abilities is warranted and may assist with targeting effective treatment plans for functional recovery.

Introduction: Abnormalities in immune function have been described in schizophrenia. Cytokines, key signaling molecules of the immune system, have been investigated in peripheral blood samples of patients with schizophrenia though few studies have investigated cytokines in cerebrospinal fluid (CSF). Moreover, very few studies with schizophrenia subjects have investigated the relationships between CSF and blood cytokine levels or investigated sex differences. Methods: In this cross-sectional study, subjects with schizophrenia spectrum disorder (SSD) diagnosis and healthy volunteers (HV) underwent a lumbar puncture, a blood draw, and psychopathology ratings. CSF and plasma levels of IL-1B, IL-2, IL-4, IL-6, IL-8 and TNFα; were determined by enzyme-linked immunosorbent assay (ELISA) and a high-sensitivity MilliplexTM Multiplex kit. Cytokine levels were square root transformed and compared between both groups using bivariate tests and a multivariate regression analysis. CSF and plasma cytokine levels were compared as were the effects of sex. Results: Thirty SSD and 23 HV were included in the study. In bivariate analysis, CSF TNFα; and IL-4 levels were significantly increased in SSD subjects compared to HV. Multivariate regression analysis also showed increases in TNFα; and IL-4 after adjusting for sex, age and body mass index. There were no significant differences in plasma cytokine levels between groups, and there were no correlations between CSF and plasma cytokine levels. CSF levels of TNFα; and IL-4 were negatively correlated with speed of processing. Stratified analysis by sex showed significantly increased levels of TNFα; and IL-4 in SSD vs. HV in males but not in females, although sample sizes were small after stratification.