BACKGROUND: Depression and depressive symptoms have been repeatedly linked to elevated levels of C-reactive protein (CRP) but questions remain as to the statistical robustness of the association and particularly whether the association between depression and CRP reflects the presence of a chronic disease. METHODS: A random sample of 6,126 men and women aged 45-69 years was examined in a cross-sectional study in seven towns in the Czech Republic. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CESD) scale. RESULTS: Center for Epidemiologic Studies Depression score was significantly related to increased levels of CRP in a linear fashion. After controlling for a range of potential confounders, subjects with depressive symptoms (CESD score >or= 16) had CRP concentrations 0.43 mg/l (95% CI 0.16-0.72) higher than those without symptoms. The association remained significant when study sample was restricted to healthy subjects; among individuals who did not report any chronic disease, the difference between those with and without depressive symptoms was 0.44 mg/l (95% CI 0.14-0.74), and among persons who did not visit a doctor in the last 12 months the difference was 1.20 mg/l (95% CI 0.52-1.87). CONCLUSIONS: These results confirm that there is a statistically robust association between depressive symptoms and increased levels of CRP. We did not find evidence that the association is due presence of a chronic condition.

• MeSH
• C-reaktivní protein analýza   MeSH
• chronická nemoc MeSH
• deprese krev   diagnóza   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• úzkostné poruchy MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• C-reaktivní protein MeSH

BACKGROUND: Schizophrenia is associated with elevated levels of circulating C-reactive protein (CRP) and other inflammatory markers, but it is unclear whether these associations extend to psychotic symptoms occurring in adolescence in the general population. A symptom-based approach may provide important clues for apparent trans-diagnostic effect of inflammation, which is also associated with depression and other psychiatric disorders. METHODS: Based on data from 2421 participants from the Avon Longitudinal Study of Parents and Children birth cohort, we examined associations of serum CRP levels assessed around age 16 with ten positive and ten negative symptoms of psychosis assessed using questionnaires around age 17, using both individual symptoms and symptom dimension scores as outcomes. Regression models were adjusted for sex, body mass index, depressive symptoms, substance use, and other potential confounders. RESULTS: Most prevalent positive symptoms were paranoid ideation (4.8%), visual (4.3%) and auditory (3.5%) hallucinations. Negative symptoms were more strongly correlated with concurrent depressive symptoms (r=0.51; P < 0.001) than positive symptoms (rpb=0.19; P < 0.001). The associations of CRP with positive and negative symptom dimension scores were similar. At individual symptom level, after adjusting for potential confounders including depressive symptoms, CRP was associated with auditory hallucinations (adjusted OR = 2.22; 95% CI, 1.04-4.76) and anhedonia (adjusted OR = 1.13; 95% CI, 1.02-1.26). CONCLUSIONS: Inflammation is associated with sub-clinical psychotic symptoms in young people in general population. Association of CRP with symptoms commonly shared between mood and psychotic disorders, such as auditory hallucinations and anhedonia, could be one explanation for the apparent trans-diagnostic effect of inflammation.

• Klíčová slova
• ALSPAC, C-reactive protein, Cohort study, Inflammation, Negative symptoms, Psychotic symptoms,
• MeSH
• C-reaktivní protein analýza   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• psychotické poruchy * epidemiologie   MeSH
• schizofrenie * epidemiologie   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• C-reaktivní protein MeSH

BACKGROUND: About every fourth patient with major depressive disorder (MDD) shows evidence of systemic inflammation. Previous studies have shown inflammation-depression associations of multiple serum inflammatory markers and multiple specific depressive symptoms. It remains unclear, however, if these associations extend to genetic/lifetime predisposition to higher inflammatory marker levels and what role metabolic factors such as Body Mass Index (BMI) play. It is also unclear whether inflammation-symptom associations reflect direct or indirect associations, which can be disentangled using network analysis. METHODS: This study examined associations of polygenic risk scores (PRSs) for immuno-metabolic markers (C-reactive protein [CRP], interleukin [IL]-6, IL-10, tumour necrosis factor [TNF]-α, BMI) with seven depressive symptoms in one general population sample, the UK Biobank study (n = 110,010), and two patient samples, the Munich Antidepressant Response Signature (MARS, n = 1058) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D, n = 1143) studies. Network analysis was applied jointly for these samples using fused graphical least absolute shrinkage and selection operator (FGL) estimation as primary analysis and, individually, using unregularized model search estimation. Stability of results was assessed using bootstrapping and three consistency criteria were defined to appraise robustness and replicability of results across estimation methods, network bootstrapping, and samples. RESULTS: Network analysis results displayed to-be-expected PRS-PRS and symptom-symptom associations (termed edges), respectively, that were mostly positive. Using FGL estimation, results further suggested 28, 29, and six PRS-symptom edges in MARS, STAR*D, and UK Biobank samples, respectively. Unregularized model search estimation suggested three PRS-symptom edges in the UK Biobank sample. Applying our consistency criteria to these associations indicated that only the association of higher CRP PRS with greater changes in appetite fulfilled all three criteria. Four additional associations fulfilled at least two consistency criteria; specifically, higher CRP PRS was associated with greater fatigue and reduced anhedonia, higher TNF-α PRS was associated with greater fatigue, and higher BMI PRS with greater changes in appetite and anhedonia. Associations of the BMI PRS with anhedonia, however, showed an inconsistent valence across estimation methods. CONCLUSIONS: Genetic predisposition to higher systemic inflammatory markers are primarily associated with somatic/neurovegetative symptoms of depression such as changes in appetite and fatigue, consistent with previous studies based on circulating levels of inflammatory markers. We extend these findings by providing evidence that associations are direct (using network analysis) and extend to genetic predisposition to immuno-metabolic markers (using PRSs). Our findings can inform selection of patients with inflammation-related symptoms into clinical trials of immune-modulating drugs for MDD.

• Klíčová slova
• Body Mass Index, C-reactive protein, Depression, Depressive symptoms, Inflammation, Interleukin 10, Interleukin 6, Network analysis, Tumour necrosis factor-α,
• MeSH
• antidepresiva terapeutické užití   MeSH
• C-reaktivní protein analýza   MeSH
• deprese * genetika   MeSH
• depresivní porucha unipolární * farmakoterapie   genetika   MeSH
• lidé MeSH
• multifaktoriální dědičnost MeSH
• zánět farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antidepresiva MeSH
• C-reaktivní protein MeSH

BACKGROUND: Meta-analyses confirm increased circulating C-reactive protein (CRP) levels in depression. Longitudinal studies have linked one-off measurements of CRP at baseline with increased risk of developing depressive symptoms subsequently at follow-up, but studies with repeat CRP measures from the same individuals are scarce. METHODS: We have examined whether longitudinal patterns of inflammation, based on three CRP measurements from childhood to early-adulthood, are associated with the risk of depression in early-adulthood in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort. RESULTS: Using Gaussian mixture modelling of available CRP data from age 9, 15 and 18 years, we identified four population clusters/sub-groups reflecting different longitudinal patterns of CRP: persistently low (N=463, 29.5%); persistently high (N=371, 24%); decreasing (N=360, 23%); increasing (N=367, 23.5%). The increasing group showed a steep increase in CRP levels between adolescence and early-adulthood. Participants in this group had a higher risk of moderate/severe depression at age 18 years, compared with those with persistently low CRP; adjusted odds ratio (OR)=3.78 (95% Confidence Interval (CI), 1.46-9.81; p=0.006). The odds of moderate/severe depression were also increased for the persistently high CRP group, but this was not statistically significant; OR=2.54 (95% CI, 0.90-7.16). LIMITATIONS: Repeat CRP measures were available for a subset, who may not be representative of all cohort participants. CONCLUSIONS: The results suggest that an increasing pattern of inflammation from adolescence to early-adulthood is associated with risk of depression in early-adulthood.

• Klíčová slova
• ALSPAC, C-reactive protein, CRP, Depression, Immunopsychiatry, Inflammation,
• MeSH
• C-reaktivní protein metabolismus   MeSH
• deprese krev   epidemiologie   MeSH
• depresivní poruchy krev   epidemiologie   MeSH
• dítě MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• prospektivní studie MeSH
• riziko MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• C-reaktivní protein MeSH