Abstract
There is increasing evidence for the role of inflammation in schizophrenia, yet the stability of increased peripheral inflammation in acute psychosis and the degree to which peripheral inflammation relates to cortical thickness, a measure of the degree of neuropathology, are unknown. In independent samples, we assessed the peripheral inflammation marker C-reactive protein (CRP) to determine the extent to which: (1) CRP was elevated and stable across admissions for acute psychosis, (2) cognition, daily function and symptom severity are characteristic of chronically ill patients with schizophrenia displaying elevated CRP, and (3) CRP levels predict cortical thickness. Study 1 assessed peripheral CRP (primary outcome) and other blood measures in 174/280 people with acute psychosis while Study 2 assessed peripheral CRP, cognition and cortical thickness (primary outcomes), symptoms, and daily function in 85/97 chronically ill patients with schizophrenia and 71/87 healthy controls. In acute psychosis, CRP and neutrophil-to-lymphocyte ratio were significantly elevated relative to a normal cutoff (with 59.8% of patients having elevated CRP) which remained elevated across admissions. CRP was significantly elevated in 43% of chronically ill patients with schizophrenia compared to 20% in controls. Elevated CRP patients displayed significantly worse working memory and CRP was inversely correlated with cortical thickness in frontal, insula, and temporal brain regions. This work supports the role of inflammation in psychotic illnesses and suggests that use of peripheral markers (e.g., CRP) in conjunction with diagnosis could be used to identify patients with more cortical neuropathology and cognitive deficits.
Highlights
Schizophrenia is a severe psychiatric disorder characterized by positive and negative symptoms, cognitive deficits, and functional decline
We made the following four hypotheses: [1] C-reactive protein (CRP) would be significantly elevated in a subgroup of chronically ill patients with schizophrenia and schizoaffective disorder relative to healthy controls, [2] cognition, symptom severity, and functional abilities would be significantly affected in patients with schizophrenia who display elevated CRP relative to those patients who display normal CRP levels, [3] CRP levels would negatively correlate with cortical thickness, and [4] CRP would be elevated to a lesser extent in chronically ill patients compared to acutely ill patients
white blood cell count (WBC) was within normal levels; there was a trend toward WBC being higher in the elevated CRP group compared to the normal CRP group, which is consistent with findings from a recent study that reported a positive relationship between leukocytes and CRP in 213 patients with schizophrenia [52]
Summary
Schizophrenia is a severe psychiatric disorder characterized by positive (e.g., hallucinations and delusions) and negative (e.g., lack of motivation) symptoms, cognitive deficits, and functional decline. The aims of Study 2 comparing chronically ill patients with schizophrenia to a healthy control group were to determine the extent to which: [1] CRP levels were elevated, [2] the proportions of patients versus controls having elevated CRP, [3] there were significant cognitive, symptom severity, and daily function differences between patients with elevated and patients with normal CRP levels, and [4] CRP levels predict cortical thickness. We made the following four hypotheses: [1] CRP would be significantly elevated in a subgroup of chronically ill patients with schizophrenia and schizoaffective disorder relative to healthy controls, [2] cognition, symptom severity, and functional abilities would be significantly affected in patients with schizophrenia who display elevated CRP relative to those patients who display normal CRP levels, [3] CRP levels would negatively correlate with cortical thickness, and [4] CRP would be elevated to a lesser extent in chronically ill patients compared to acutely ill patients (comparing results from Study 1 and Study 2).
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