C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review

Abstract

Objectives: The objective of this systematic review was to synthetize the published data on the relationships between elevated blood C-reactive protein (CRP) levels and schizophrenia (SZ) onset risk, illness characteristics and treatments, cognition and physical health.Method: The systematic bibliographic searches have been carried out according to the Cochrane methodology. Medline, web of science, Google Scholar with each database being searched from inception to November 2017.Results: 53 studies were included in the present review. While meta-analyses including case-control studies suggest a clear association between CRP and SZ, one other study has suggested that CRP-associated genes were associated with a lower risk of SZ onset. Increased CRP has been significantly associated with positive symptoms in acute phase psychosis, while studies including community-dwelling stabilized subjects did not find such an association. Abnormal CRP has been associated with a wide range of cognitive impairment in SZ stabilized individuals. Body Mass index has been extensively associated with increased CRP in SZ subjects; and increased CRP has been identified as a risk factor for metabolic syndrome and cardiovascular risk in SZ subjects. Increased CRP has also been associated with high nicotine dependence in SZ smokers and one study has suggested that increased CRP was associated with sedentary behavior.Conclusion: In the light of the above-mentioned studies, increased hs-CRP may be reasonably suggested as a marker for SZ onset risk, as well as a risk factor for increased positive symptoms, cognitive impairment, hypovitaminosis D, microbiota disturbances, cardiovascular and metabolic syndrome risk in SZ subjects, and increased nicotine dependence in SZ smokers. In case of increased CRP levels, anti-inflammatory strategies (add-on anti-inflammatory drugs including aspirin and omega 3 fatty acids, vitamin D supplementation, physical activity, probiotics) should be also further evaluated.Limits: Most of the studies were cross-sectional and cohort studies are needed to determine the temporal relationship between increased CRP and the psychiatric outcomes.

The Role of Inflammation in the Treatment of Schizophrenia

“…We have seen that defining an inflammation signature in schizophrenia was difficult due to the multiple cytokines that may be disturbed according to the state of the illness. We have recently published a review on the interest of hs-CRP to identify peripheral inflammation in schizophrenia (29). Hs-CRP is the most common peripheral marker of inflammation and is synthesized by the liver in response to IL-1 and IL-6 according to the following pathway.…”

Microbiota-Orientated Treatments for Major Depression and Schizophrenia

“…Abnormal bacterial markers have been identified in the blood of SZ patients [22,23]. Emerging data show that about 30% of SZ people have elevated antigliadin antibodies (AGA) of the IgG type, representing a possible subgroup of schizophrenia patients with increased gut permeability [24]. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood-brain barrier with resulting neuroinflammation Our hypothesis is that replacing the whole microbiota of SZ-MD patients (the so-called fecal microbiota transplantation (FMT)) may improve their mental and physical health, and more specifically their depressive symptoms and quality of life.…”

Cognitive impairment and C-reactive protein in clinically stable schizophrenia outpatients: a focus on sex differences

“…C-reactive protein (CRP) represents a reliable, easy, and inexpensive marker of peripheral inflammation 4 . Plasmatic CRP has been found to correlate with central immune activity in patients with psychiatric disorders 5 , and recent literature shows a growing interest in its potential role as a biomarker of schizophrenia 6 . Elevated CRP levels have been associated with more severe psychopathology and a wide range of impaired cognitive functions in SZ in both inpatient and outpatient samples 6 , as well as in other chronic psychiatric syndromes such as bipolar disorder (BD) 7 .…”

“…Plasmatic CRP has been found to correlate with central immune activity in patients with psychiatric disorders 5 , and recent literature shows a growing interest in its potential role as a biomarker of schizophrenia 6 . Elevated CRP levels have been associated with more severe psychopathology and a wide range of impaired cognitive functions in SZ in both inpatient and outpatient samples 6 , as well as in other chronic psychiatric syndromes such as bipolar disorder (BD) 7 . Sex and hormonal status could play a role in determining this association, and in a community-dwelling elderly population, the relationship between CRP concentration and cognitive decline was observed only in women 8 .…”

“…5 Instituto de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain. 6 Departamento de Psicología, Universidad de Oviedo, Oviedo, Spain. 7 Centro de Salud Mental La Corredoria, Alfredo Blanco s/n, Oviedo, Spain.…”