Elsevier

Journal of Affective Disorders

Volume 225, 1 January 2018, Pages 671-675
Journal of Affective Disorders

High C-reactive protein levels are associated with depressive symptoms in schizophrenia

https://doi.org/10.1016/j.jad.2017.09.004Get rights and content

Highlights

  • Chronic Inflammation plays a crucial role in the pathophysiology of schizophrenia.

  • Chronic inflammation can be easily assessed with C - Reactive Protein (CRP) level.

  • High CRP level is associated with depressive symptoms in patients with schizophrenia.

  • High CRP level is not associated with antidepressant consumption in patients with schizophrenia.

Abstract

Background

Depressive symptoms are frequently associated with schizophrenia symptoms. C - Reactive protein (CRP), a marker of chronic inflammation, had been found elevated in patients with schizophrenia and in patients with depressive symptoms. However, the association between CRP level and depressive symptoms has been poorly investigated in patients with schizophrenia. The only study conducted found an association between high CRP levels and antidepressant consumption, but not with depressive symptoms investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS).

Objectives

The aim of this study was to evaluate CRP levels and depressive symptoms in patients with schizophrenia, and to determine whether high CRP levels are associated with depressive symptoms and/or antidepressant consumption, independently of potential confounding factors, especially tobacco-smoking and metabolic syndrome.

Methods

Three hundred and seven patients with schizophrenia were enrolled in this study (mean age = 35.74 years, 69.1% male gender). Depressive symptoms was investigated with the CDSS. Patients were classified in two groups: normal CRP level (≤ 3.0 mg/L) and high CRP level (> 3.0 mg/L). Current medication was recorded.

Results

124 subjects (40.4%) were classified in the high CRP level group. After adjusting for confounding factors, these patients were found to have higher CDSS scores than those with normal CRP levels in multivariate analyses (p = 0.035, OR = 1.067, 95% CI = 1.004–1.132). No significant association between CRP levels and antidepressants consumption was found.

Limitations

The size sample is relatively small. The cut-off point for high cardiovascular risk was used to define the two groups. CRP was the sole marker of inflammation in this study and was collected at only one time point. The design of this study is cross-sectional and there are no conclusions about the directionality of the association between depression and inflammation in schizophrenia.

Conclusion

This study found an association between high rates of CRP levels and depressive symptoms in patients with schizophrenia, but no association with antidepressant consumption. Further studies are needed to investigate the impact of inflammation in schizophrenia.

Introduction

Schizophrenia occurs in around approximately 1% of the population worldwide and around 0.6–0.8% in France (McGrath et al., 2008). It is a chronic disease characterized by psychotic symptoms, cognitive impairment and functional decline (Dickinson et al., 2004, Bruijnzeel and Tandon, 2011). Depressive symptoms are also frequently associated in schizophrenia (Tandon et al., 2009, Andrianarisoa et al., 2017). Prevalence rates of major depressive disorder (MDD) in schizophrenia range from 30% to 70% (Majadas et al., 2012, Peitl et al., 2016). Presence of depressive symptoms in patients with schizophrenia has been associated with overall worse outcomes, greater comorbidity, poorer quality of life (Andrianarisoa et al., 2017), work impairment, deterioration of psychosocial functioning, greater risk of relapse and increased risk of suicide (Tandon et al., 2009). Better understanding of the pathophysiology of depressive symptoms in schizophrenia is thus necessary.

The contribution of chronic inflammation to major mental disorders has received increased attention in the last decade (Fond et al., 2014). Among other inflammatory factors, C-reactive protein (CRP) is a nonspecific marker that has the following two advantages: i) it is easily measured in blood samples, and ii) it provides a reliable marker of chronic inflammation. CRP was first extensively studied as a predictor of cardiovascular disease (Emerging Risk Factors Collaboration et al., 2010), which is one of the leading causes of early mortality in patients with schizophrenia (Mitchell et al., 2013). Moreover, CRP levels were found elevated in patients with schizophrenia (Miller et al., 2014) and in patients with MDD (Howren et al., 2009, Strawbridge et al., 2015, Valkanova et al., 2013). In schizophrenia patients, high CRP levels have been associated not only with cardiovascular risk but also with more psychotic symptoms (Fan et al., 2007), with greater cognitive impairment (Dickerson et al., 2007, Dickerson et al., 2012, Bulzacka et al., 2016), and with greater sensory processing impairment (Micoulaud-Franchi et al., 2015) than in patients with low CRP levels. In patients with MDD, high CRP levels are considered to be a useful biomarker for predicting the risk of major depressive episode (Duivis et al., 2013, Wium-Andersen et al., 2014), and have been associated with the persistence of depressive symptoms under treatment (Zalli et al., 2016) and with differential response rates to antidepressants (Uher et al., 2014). However, whereas CRP levels are known to be associated with MDD, their association with depressive symptoms in schizophrenia has received little attention. Fond et al. (2016) found an association between high CRP levels in schizophrenia and antidepressant consumption, but not with depressive symptoms investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS).

This study sought to evaluate CRP levels and the level of depressive symptoms investigated with the CDSS but also to determine the prevalence of high CRP levels, MDD and antidepressant consumption rates in a sample of patients with stable schizophrenia. We sought to determine whether high CRP levels are associated with depressive symptoms and/or antidepressant consumption in patients with schizophrenia, independently of potential confounding factors, especially tobacco-smoking and metabolic syndrome.

Section snippets

Study participants

The study evaluated all prospective patients attending daytime hospital hours in our university and psychiatric hospital over a period of 5 years from June 2010 to June 2015. The inclusion criteria were as follows: (1) age 18–85 years old, (2) diagnosis of schizophrenia according to the DSM-IV-TR criteria, (3) antipsychotic and possibly antidepressant or mood stabilizing agent medication stable for a minimum of 3 months, and (4) French as native language. The exclusion criteria were as follows:

Patient characteristics

Three hundred and seven patients with schizophrenia participated in the study (Table 1). The mean age of the patients was 35.74 years (± 11.61), and 69.1% were male. They had moderately severe symptoms with a mean PANSS total score of 73.79 (± 20.93), and a mean 5-factor scores of 28.41 (± 9.63), 17.67 (± 7.17), 8.99 (± 3.92), 11.28 (± 4.37) and 7.42 (± 2.97) for negative, positive, excited, depressive and cognitive factors. Of the total number of patients, 29.3% were treated by antidepressants

Discussion

This study investigated the prevalence of high CRP levels, MDD and antidepressant consumption and the relationship between depressive symptoms and high CRP levels in patients with schizophrenia. Our findings provide evidence for a high prevalence of high CRP levels in our sample of patients with schizophrenia. The prevalence of high CRP levels (40.4%) is comparable with the global prevalence of abnormal CRP levels found in our previous study (Faugere et al., 2015) and in other studies (

Limitations and perspectives

Several limitations should be considered in this study. First, the size of the sample is relatively small, and further researches should replicate the findings in larger studies. Second, there is the problem of the definition of the groups (normal and high CRP level according to a 3.0 mg/L threshold). While there are no generally accepted criteria for the threshold, we chose the most consensual threshold in the recent scientific literature, which is recognized as the cut-off point for high

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Acknowledgements

Our thanks to all the patients and staff who helped with the study.

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