Association between CRP genetic diversity and bipolar disorder comorbid complications

Abstract

BackgroundChronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD.Methods568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3′-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders.ResultsWe found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004).ConclusionsOverall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.

Roles of C-reactive protein polymorphisms and life event changes on cognitive function in bipolar patients receiving valproate

“… 81 , 84 Although a previous study also reported that the frequencies of the CRP polymorphisms were similar between the BD and control groups, the polymorphisms of CRP genetic diversity might contribute to the development of autoimmune comorbid disorders and rapid cycling, which are both representative of BD severity. 85 Taken together, the results from the study suggest that although polymorphisms of CRP might not be associated with plasma CRP levels in BD, polymorphisms could be linked to treatment outcome in cases of BD.…”

Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression

“…They concluded that low grade inflammation might play a role in mania and might be rather a state than a trait marker of bipolar disorder. Lastly, Boukouaci et al (2018) suggested that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. They concluded that such findings might predict complex clinical presentations of the disease leading to precision medicine in psychiatry.…”

Rapid cycling bipolar disorder: Literature review on pharmacological treatment illustrated by a case report on ketamine

“…They concluded that these findings support a role of the altered peripheral immune response in RCBD. In a large cohort, some authors found that in a subgroup of patients, a CRP gene variant is associated with thyroid disorders and mostly with rapid cycling, especially in women (Boukouaci et al., 2018 ). Another study found higher levels of IL‐8, MCP‐1, IFN‐γ, IL‐6, TNF‐α in nonresponder depressed bipolar patients compared to responders (Benedetti et al., 2017 ).…”