High C-reactive protein levels are associated with depressive symptoms 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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2022, Schizophrenia ResearchCitation Excerpt :IL-6 and TNF-α in particular are known to induce acute phase proteins of inflammation such as CRP through gene expression activation in the liver (Baumann and Gauldie, 1994). Some studies have thus highlighted significant correlations between CRP levels and clinical dimensions of schizophrenia which can be exacerbated in acute episodes such as positive symptoms (Dimitrov et al., 2016; Bolu et al., 2019; Steiner et al., 2020), agitation and aggressivity (Barzilay et al., 2016; Zhang et al., 2017; Kachouchi et al., 2020), negative symptoms (Garcia-Rizo et al., 2012; Boozalis et al., 2017), cognitive impairment (Dickerson et al., 2007; Bulzacka et al., 2016; Zhu et al., 2019), depressive symptoms (Faugere et al., 2018) and even suicidal risk (De Berardis et al., 2013). Our data which found higher CRP levels in acutely ill patients as compared to stable patients are thus in accordance with the hypothesis of the vulnerability-stress-inflammation model of schizophrenia (Howes and McCutcheon, 2017).
Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population
2020, EncephaleCitation Excerpt :CRP, which plays a pivotal role in the innate immune system and has pleiotropic effects [7–9], belongs to the pentraxin family and is synthesized by the liver after induction by interleukin (IL)-6 [9]. There is a growing evidence of the implication of CRP in the pathogenesis of SZ [10–15] as exemplified by numerous epidemiological studies highlighting association between elevated high sensitive assay CRP levels (hs-CRP) and schizophrenia [16–19]. Moreover, compelling data strongly suggest that both expression and systemic levels of CRP may be influenced by genetic variations [20,21].
Abnormal C-reactive protein blood levels as a specific biomarker of major depression and non-remission under antidepressants in schizophrenia
2020, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Beyond SZ, increased CRP has been extensively associated with depressive symptoms in general population and mood disorders, and antidepressants have been found to have anti-inflammatory effects (Hannestad et al., 2011). On the contrary, conflicting results were found for the association between CRP and depressive symptoms as well as on the effect of antidepressants in SZ patients (Faugere et al., 2018; Fond et al., 2016). Given that SZ and UD have been associated with different immunological disturbances, these different immune-inflammatory signatures may explain these discrepancies.