Search

Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drug-naïve or short-time medicated first episode psychosis (FEP) patients., Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay., Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in >50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls., Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exact mechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Impaired expression and function of several major neurotrophic factors such as nerve growth factor (NGF) has been proposed to contribute to the neurodevelopmental pathology of schizophrenia. However, the evidence in the majority of studies is based on variable and inconsistent levels of plasma NGF in diverse populations of early psychosis or medicated patients with chronic schizophrenia. We report here the first study comparing NGF levels in cerebrospinal fluid (CSF) and plasma from a unique patient cohort (unmedicated, early psychotic patients with similar racial and dietary patterns) and matched healthy controls. Significantly lower levels of NGF in both CSF (p=0.038) and plasma (p=0.002) were observed in drug-naïve first-episode psychosis patients as compared to controls. The levels of NGF in the CSF correlated (p=0.05) to the plasma values in controls. The data on plasma NGF confirm the reported deficits of NGF in drug-naïve first-episode psychosis. The reduced levels first time observed here may have important implications to repeatedly reported neurobiological and clinical deficits which are discussed.

Introduction: There is evidence for a relationship between low levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and suicidal behavior in mood disorder. A relationship between CSF homovanillic acid (HVA) and suicidal behavior has not been completely established. Studies done in patients with schizophrenia spectrum psychosis suffer from small numbers, short periods of follow-up and the results are contradictory. The objective of this study was to investigate the relationship between levels of CSF 5-HIAA, CSF HVA and suicidal behavior in patients with schizophrenia spectrum psychosis., Method: Three hundred eighty five patients with schizophrenia spectrum psychosis admitted to the Karolinska University Hospital between 1973 and 1987 were lumbar punctured in standardized manner. Patients were followed until 2006 for a median of 26 years. Information about prior suicide attempt was retrieved from medical records and causes of death were obtained from the Causes of Death Register at the National Board of Health and Welfare., Results: At the end of the follow-up 26 patients (6.8%) had died by suicide. Male gender (OR=3.5) and attempted suicide (OR=12.4) were risk factor for suicide when combined. There were no significant correlations between levels of CSF 5-HIAA, CSF HVA, HVA/5-HIAA ratio and attempted, violent or non-violent suicide., Conclusion: Male schizophrenia spectrum psychosis patients with prior suicide attempt are at high risk for suicide. No correlation between CSF monoamine metabolites levels and suicidal behavior was found. Suicidal behavior in schizophrenia spectrum psychosis may not, in contrast to mood disorders, be predicted by levels of CSF 5-HIAA and HVA.

Background: Previous studies have shown that cerebrospinal fluid (CSF) from schizophrenic patients contains significantly higher levels of the endogenous cannabinoid anandamide than does CSF from healthy volunteers. Moreover, CSF anandamide levels correlated inversely with psychotic symptoms, suggesting that anandamide release in the central nervous system (CNS) may serve as an adaptive mechanism countering neurotransmitter abnormalities in acute psychoses. In the present study we examined whether cannabis use may alter such a mechanism., Methods: We used liquid chromatography/mass spectrometry (LC/MS) to measure anandamide levels in serum and CSF from first-episode, antipsychotic-naïve schizophrenics (n=47) and healthy volunteers (n=81). Based on reported patterns of cannabis use and urine delta9-tetrahydrocannabinol (delta9-THC) tests, each subject group was further divided into two subgroups: 'low-frequency' and 'high-frequency' cannabis users (lifetime use < or = 5 times and > 20 times, respectively). Serum delta9-THC was investigated to determine acute use and three patients were excluded from the analysis due to detectable delta9-THC levels in serum., Results: Schizophrenic low-frequency cannabis users (n=25) exhibited > 10-fold higher CSF anandamide levels than did schizophrenic high-frequency users (n=19, p=0.008), healthy low-frequency (n=55, p<0.001) or high-frequency users (n=26, p<0.001). In contrast, no significant differences in serum anandamide levels were found among the four subgroups. CSF anandamide levels and disease symptoms were negatively correlated in both user groups., Conclusions: The results indicate that frequent cannabis exposure may down-regulate anandamide signaling in the CNS of schizophrenic patients, but not of healthy individuals. Thus, our findings suggest that alterations in endocannabinoid signaling might be an important component of the mechanism through which cannabis impacts mental health.

The authors examined the effects of antipsychotic treatment on cerebrospinal fluid somatostatin like immunoreactivity (CSF SLI) in 14 schizophrenic and 3 schizoaffective patients. There was a modest but significant increase in CSF SLI in 13 out of the 14 schizophrenic patients. In addition, there was a significant positive correlation between duration of treatment and post-treatment CSF SLI concentrations. No differential response was noted in patients also treated with the anticholinergic benztropine.