Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation.

Dorota Frydecka,Anna Tomkiewicz,Jan Aleksander Beszłej,Andrzej Kiejna,Lidia Karabon,Edyta Pawlak-Adamska,Paweł Sedlaczek,Błażej Misiak

doi:10.1007/s00406-014-0533-5

Dorota Frydecka, Anna Tomkiewicz + Show 6 more

Open Access

https://doi.org/10.1007/s00406-014-0533-5

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Abstract

The influence of the immune system deregulation on the risk of schizophrenia is increasingly recognized. The aim of this study was to assess the influence of serum interleukin-6 (IL-6) level together with the polymorphism in its gene (IL6 -174G/C) and high sensitivity C-reactive protein (hsCRP) levels on clinical manifestation and cognition in schizophrenia patients. We recruited 151 patients with schizophrenia and 194 healthy control subjects. Psychopathology was evaluated using Operational Criteria for Psychotic Illness checklist, Positive and Negative Syndrome Scale (PANSS) and Scales for Assessment of Positive and Negative Symptoms. Cognitive performance in schizophrenia patients was assessed using following tests: Rey Auditory Verbal Learning Test, Trail Making Test, Verbal Fluency Tests, Stroop and subscales from Wechsler Adults Intelligence Scale-R-Pl (Similarities, Digit Symbol Coding, Digit Span Forward and Backward). Serum IL-6 and hsCRP levels were significantly higher in schizophrenia patients in comparison with healthy controls. Both hsCRP and IL-6 levels were associated with insidious psychosis onset, duration of illness and chronic schizophrenia course with deterioration. After adjustment for age, education level, number of years of completed education, illness duration, total PANSS score, depression severity and chlorpromazine equivalent, there was still a positive association between IL-6 and hsCRP levels and worse cognitive performance. The IL6 -174G/C polymorphism did not influence IL-6 level, but it was associated with the severity of positive symptoms. Our results suggest that elevated IL-6 levels may play the role in cognitive impairment and serve as potential inflammatory biomarker of deterioration in schizophrenia.

Highlights

Interleukin-6 (IL-6) is a multifactorial cytokine that is implicated in hematopoiesis, metabolic control, bone metabolism and nociceptive regulation [1]
We found no significant difference between the variables that may influence the relationship between the IL-6 gene (IL6) -174G/C polymorphism and IL-6 levels, such as age, gender, chlorpromazine equivalent, illness duration, cigarette smoking and Body mass index (BMI) across the IL6 -174G/C genotypes (Table 3)
The influence of the immune system deregulation on the risk of schizophrenia has been reported for years ; the association between C-reactive protein (CRP) and IL-6 with

Summary

Introduction

Interleukin-6 (IL-6) is a multifactorial cytokine that is implicated in hematopoiesis, metabolic control, bone metabolism and nociceptive regulation [1]. IL-6 has been implicated in the pathophysiology of schizophrenia. The first meta-analysis of cytokine alterations in schizophrenia patients provided that IL-6 level is increased in this group of patients [2]. These findings are in line with animal models showing that IL-6 promotes the survival of catecholaminergic neurones as well as stimulates serotonergic and dopaminergic transmission in the hippocampus and prefrontal cortex [3]. Emerging evidence indicates that IL-6 level is increased already in subjects with at-risk mental state (ARMS) and might be a marker of transition from ARMS to schizophrenia [5]

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