[Show abstract][Hide abstract] ABSTRACT: Depression has been associated with chronic changes in the serum concentration of C-reactive protein (CRP) in observational studies, but it is unclear if this association is causal or is due to confounding and bias. Genetic studies are less subject to this type of error and offer an opportunity to investigate if CRP is causally linked to depression, particularly because known polymorphisms of the CRP gene have been associated with high- and low-basal serum concentrations of CRP [single nucleotide polymorphisms (SNPs) rs1130864 and rs1205, respectively]. The aim of this study is to determine if polymorphisms of SNPs rs1130864 and rs1205 are associated with prevalent depression.
We completed a cross-sectional study of a community sample of 3700 men aged > or = 70 years, and used the 15-item Geriatric Depression Scale (GDS-15) to assess depressive symptoms. A GDS-15 score 7 or more indicates the presence of clinically significant depressive symptoms. Physical morbidity was assessed with the physical component summary score (PCS) of the SF-36 Health Survey. We collected fasting blood samples to measure high sensitivity CRP and to extract DNA for the genotyping of SNPs rs1130864 and rs1205 of the CRP gene.
One hundred and eighty-two men were depressed (4.9%). The odds of depression increased by 2% (95% CI = 1-4%) for every unit (mg/l) increase of CRP and nearly doubled for men with CRP > or = 3 mg/l vs <1 mg/l [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.27-2.98]. However, the association between high CRP (> or = 3 mg/l) and depression was no longer significant after the analyses were adjusted for smoking, age, body mass index (BMI) and PCS. Men with the CT and TT genotypes of rs1130864 had 1.36 (95% CI = 1.13-1.63) and 2.31 (95% CI = 1.65-3.24) greater odds of CRP > or = 3 mg/l than CC carriers, but there was no association between this polymorphism and the presence of prevalent depression. The G > A polymorphism of SNP rs1205 was associated with 24% (95% CI = 16-32%) lower concentration of CRP compared with other genotypes. Men with the rs1205 AA genotype had 1.66 (95% CI = 1.07-2.57) and 1.67 (95% CI = 1.08-2.58) greater odds of having clinically significant depression than participants with the GA and GG genotypes, respectively.
Our study shows that clinically significant depressive symptoms in later life are unlikely to be caused by an increase in the serum concentration of CRP. Instead, we found that the risk of depression was greater amongst people who carry the rs1205 G > A genetic polymorphism of the CRP gene, which was associated with approximately 20% lower serum concentration of CRP compared with other genotypes. This suggests that CRP may be a compensatory response to external insults that predispose to depression, and that an increase in the concentration of CRP might be adaptive.
International Journal of Epidemiology 05/2009; 38(4):1049-59. DOI:10.1093/ije/dyp199 · 9.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: A series of epidemiological, clinical and laboratory findings suggest an autoimmune process in schizophrenia and include, among others, high titers of various autoantibodies in the sera of patients. Antiribosomal P antibody is known to exist in systemic lupus erythematosus (SLE) patients with a psychiatric presentation, including psychosis, rationalizing the examination of its existence in patients with schizophrenia. Methods: Sera of 59 patients, 48 diagnosed with schizophrenia and 11 diagnosed with a schizoaffective disorder, were examined for the presence of antiribosomal P antibody titers using ELISA. The control group consisted of 94 healthy subjects with similar age and gender distribution. Results: Anti-ribosomal P antibody titers were below cut-off level in 58 patients and borderline in one patient, similar to the low titers of the control group. Conclusions: Previous investigations have demonstrated high specificity for anti-ribosomal P antibody in SLE patients with psychosis. In view of the results of this study, however, anti-ribosomal P antibody is not a biological marker for schizophrenia.
The Israel journal of psychiatry and related sciences 01/2011; 48(4):275-279. · 0.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is compelling clinical literature implicating a role for cytokines in the pathophysiology of major depressive disorder (MDD). Interleukin-6 (IL-6) and interleukin-1β (IL-1β) are pleiotropic inflammatory cytokines that have been reported to be elevated in patients with MDD. The present studies were undertaken to investigate the relationship between IL-6 and IL-1β in animal models of depressive-like behavior. Analysis of brain tissue homogenates in the cortex of rats subjected to chronic stress paradigms revealed elevated levels of IL-6 protein in the absence of elevations in IL-1β. Central administration of recombinant mouse IL-6 produced depressive-like phenotypes in mice, which were not accompanied by IL-1β-induced increases in the brain tissue or IL-1β-related sickness behavior typical of a general central nervous system inflammatory response. Systemic administration of fluoxetine in the presence of centrally administered IL-6 failed to produce the expected antidepressant-like response in mice relative to sham-infused controls. Further, administration of fluoxetine to mice with endogenous overexpression of brain IL-6 (MRL/MpJ-Fas(LPR/LPR) (LPR mice)) failed to produce the expected antidepressant-like effect relative to fluoxetine-treated control mice (MRL/MpJ(+/+)). Interestingly, blockade of IL-6 trans-signaling by coadministration of a gp130/Fc monomer or an anti-mouse IL-6 antibody with IL-6 prevented the IL-6-induced increases in immobility time as well as attenuated IL-6-induced increases of protein in the cortex. Taken together, these data indicate that elevations in IL-6 may have a pathophysiological role underlying depression and more specifically resistance to current classes of antidepressant medications and suggest that modulation of the IL-6 signaling pathway may have therapeutic potential for treatment-resistant depression.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.