Association between C-reactive protein and depression: modulated by gender and mediated by body weight

Background Studies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics. Methods We estimated seven regularized Mixed Graphical Models in the Netherlands Study of Depression and Anxiety (NESDA) data (N = 2321) to explore shared variances among (1) depression severity, modeled via depression sum-score, nine DSM-5 symptoms, or 28 individual depressive symptoms; (2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); (3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases. Results The depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al., CRP was associated with ‘sleep problems’, ‘energy level’, and ‘weight/appetite changes’; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms ‘insomnia’, ‘hypersomnia’, and ‘aches and pain’ showed unique positive relations to all inflammatory markers. Conclusions We found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.

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Section: Discussionsupporting

confidence: 90%

Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates

et al. 2019

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“…Our results show that relationships between depression and inflammation are strongly attenuated after BMI adjustment. This is consistent with some studies in the literature (Elovainio et al 2009;Liu et al 2014), but contrasts with other results of more robust associations (Haapakoski et al 2015b be that weight represents a major explanatory factor that accounts for the link between depression and inflammation, and that inflammation can occur in depressed patients because certain depressive symptoms emerge as a result from a shared pathophysiology with obesity and metabolic conditions (Lamers et al 2017;Milaneschi et al 2018). Future studies may benefit from more closely investigating weight changes and obesity, given that waist circumference and waist-to-hip ratio have been shown to relate to CRP (Choi et al 2013).…”

Section: Discussionsupporting

confidence: 86%

Using network analysis to examine links between individual depression symptoms, inflammatory markers, and covariates

Fried¹,

Haslbeck²

2018

Preprint

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Background. Studies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics.Methods. We estimated seven regularized mixed graphical models in the NESDA data (N=2321) to explore shared variances among 1) depression severity, modeled via depression sum-score, 9 DSM-5 symptoms, or 28 individual depressive symptoms; 2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); 3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases.Results. The depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al. (2016), CRP was associated with 'sleep problems', 'energy level', and 'weight/appetite changes'; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms 'insomnia, 'hypersomnia', and 'aches and pain' showed unique positive relations to all inflammatory markers. Conclusions.We found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.

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“…The results show elevated CRP levels in patients hospitalized due to manic exacerbation compared to depressed exacerbation, suggesting that, in affective patients, manic polarity has a stronger link to inflammation compared to depressed polarity. The results of this study concur with recent reports suggesting increased immune activation in bipolar patients compared to non-bipolar patients [2, 3, 7, 9, 16-20], and increased immune activation in manic patients compared both to the non-manic bipolar patients and the non-bipolar patients [9, 14, 15, 17, 21-23]. However, in those studies, patients were selected and categorized based on their DSM diagnoses, while we employed a transdiagnositc approach and included all inpatients with acute affective exacerbation leading to hospitalization, regardless of their primary DSM diagnoses.…”

Section: Discussionsupporting

confidence: 93%

“…Inflammation has gained much interest as data accumulates to point its association with psychopathological symptoms [2-7]. The role of inflammation in the pathophysiology of affective disorders has been widely investigated during the last decade, with a growing support regarding a putative link between the two [3, 8-10].…”

Section: Introductionmentioning

confidence: 99%

Association between Elevated C-Reactive Protein and Manic Polarity in Acute Psychiatric Inpatients with Affective Symptomatology

et al. 2017

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The interplay between the immune system and behaviour is of increasing interest in psychiatry research. Specifically, accumulating data points to a link between inflammation and psychopathology, including affective symptomatology. We investigated the association between inflammation and affective polarity in psychiatric inpatients who were hospitalized due to an affective exacerbation. Data was collected retrospectively and comparisons were made between manic and depressed patients. C-reactive protein (CRP), a general laboratory marker of immune activation and inflammation, was used as a non-specific inflammatory biomarker. Age, smoking and body mass index were considered covariates. Manic polarity (n = 89) was associated with statistically significant elevated CRP levels compared to depressed polarity (n = 44, 56%; p = 0.036), after controlling for covariates. No differences were observed in CRP levels across Diagnostic and Statistical Manual of Mental Disorders-IV Edition-Text Revised psychiatric diagnoses. These findings suggest a transdiagnostic association between inflammation and manic polarity in affective inpatients.

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Association between C-reactive protein and depression: modulated by gender and mediated by body weight

Cited by 46 publications

References 38 publications

Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates

Using network analysis to examine links between individual depressive symptoms, inflammatory markers, and covariates

Using network analysis to examine links between individual depression symptoms, inflammatory markers, and covariates

Association between Elevated C-Reactive Protein and Manic Polarity in Acute Psychiatric Inpatients with Affective Symptomatology

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