Polygenic risk for immuno-metabolic markers and specific depressive symptoms: A multi-sample network analysis study

Kappelmann, Nils; Rost, Nicolas; Moser, Sylvain; Schmoll, Vanessa; Trastulla, Lucia; Štochl, Jan; Lucae, Susanne; Binder, Elisabeth B.; Khandaker, Golam; Arloth, Janine

doi:10.1016/j.bbi.2021.03.024

Cited by 39 publications

(27 citation statements)

References 88 publications

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“…41 In keeping with these findings, polygenic scores influencing higher CRP levels were positively associated with increasing altered appetite and fatigue (along with TNF-α), suggesting that genetic predisposition to higher systemic inflammatory markers are primarily associated with somatic/neurovegetative symptoms of depression. 42 This evidence was supported by a multi-sample network analysis in depressed and general population cohorts, and is also consistent with previous observational studies on circulating inflammation markers in population cohorts. 7,43 Moreover, Mendelian randomization analyses suggested a causal effect of increased CRP on somatic symptoms (appetite alterations, tiredness/…”

Section: Discussionsupporting

confidence: 90%

Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms

Gialluisi¹,

Santonastaso²,

Bonaccio³

et al. 2021

JIR

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Background Depression is a mood disorder characterized by a high rate of resistance to pharmacological treatments, which has often been linked to chronic inflammation. This can be influenced by different environmental factors, in particular pro-inflammatory diets. However, a mediating role of circulating inflammation has never been observed. Aim To test the association between a dietary inflammatory index (DII ® ) and continuous depressive symptoms (adapted version of PHQ9) in an Italian population cohort (N=13,301), along with potential explanatory effect of a composite index (INFLA-score) based on four circulating inflammatory biomarkers: C-reactive protein, granulocyte-to-lymphocyte ratio, platelet and white blood cell counts. Results Significant positive associations were observed between DII and total depressive symptoms (standardized β (SE) = 0.038 (0.005), p < 0.001), and with two factors tagging somatic (0.012 (0.003), p < 0.001) and cognitive symptoms (0.012 (0.003), p < 0.001), after adjustment for different potential confounders (socioeconomic status, chronic health conditions and lifestyles). These associations were about twice as strong in women than in men. INFLA-score explained a small but significant proportion of the association with total depressive symptoms (0.90–2.30%, p < 0.05), which was mainly driven by granulocyte-to-lymphocyte ratio (1.18–1.65%). This effect was even stronger for the somatic (2.66–4.66%) but not for the cognitive factor (0%). Conclusion These findings support a strong link between inflammatory diet and depression, especially with somatic symptoms and within women. Moreover, they provide novel evidence for a potential explanatory role of circulating inflammation in this association, suggesting new paths for prevention and treatment of major and atypical depression.

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Section: Discussionsupporting

confidence: 90%

Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms

Gialluisi¹,

Santonastaso²,

Bonaccio³

et al. 2021

JIR

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“…Significant enrichment of genes involved in protein degradation pathways as well as the predictive capacity of risk for cardioembolic stroke, however, support a link between LLD and risk for vascular dysfunction [ 198 ]. Other large GWAS data showed co-heritability between CRP levels and individual depressive symptoms [ 199 ] and that inflammatory markers are associated with neurovegetative symptoms of depression [ 200 ]. A GWAS of cognitive functional decline in individuals with LLD identified candidate genes, including SLC27A1, involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective component in the brain that is reduced in these patients [ 201 ].…”

Section: Challenging Pathomechanismsmentioning

confidence: 99%

“…Since VaD is often associated with increased inflammation biomarkers [ 105 ], neuroinflammation may be a key therapeutic target for therapeutic strategies in LLD [ 66 , 200 ], and a meta-analysis suggested that nonsteroidal anti-inflammatory agents (NSAID) and cytokine antagonists have antidepressant properties in relevant patients [ 229 ]. Efficacious psychotherapies for LLD may include streamlined, neurobiologically based methods targeting behavioral domains assumed to result from dysfunctions of specific brain networks [ 33 ], or neuroplasticity-based computerized cognitive remediation programs [ 230 ], but their effectiveness needs to be validated.…”

Section: Implications For Clinical Practice and Managementmentioning

confidence: 99%

Pathomechanisms of Vascular Depression in Older Adults

Jellinger¹

2021

IJMS

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Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto–limbic and other important neuronal networks, may contribute to the development of LLD. The “vascular depression” hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

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“… 42 These results differ from the findings of the current study. Similarly, the application of the network model has considered the assessment of polygenic risk measures of BMI, as observed in the study by Kappelmann et al, 43 who evaluated 3 national samples and found that, in 2 of them, the polygenic risk measure of BMI presented a greater association with the items “Low interest and dissatisfaction” (PH1) and “Problems with sleep” (PH3). This finding is consistent with our results that evidenced higher scores of depressive symptoms in the obesity group.…”

Section: Discussionmentioning

confidence: 99%

Network Analysis of Depressive Symptomatology in Underweight and Obese Adults

Ramos-Vera

Serpa

Saldarriaga

et al. 2022

J Prim Care Community Health

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Background: Depressive symptoms can affect people’s quality of life and social environment. In addition, in severe situations, they can lead to suicidal behaviors. Objective: This study aimed to analyze the differences in depressive symptoms in underweight and obese Peruvian adults. Methods: A cross-sectional study was carried out based on secondary data obtained from the Instituto Nacional de Estadística e Informática (INEI), Lima, Peru. A sample of 10 053 participants was considered, of which 55.96% were women. Two Gaussian plot models were estimated and the levels of depressive symptomatology were compared between the 2 groups (adults with underweight and obese). Results: A total of 1510 (15.02%) were underweight adults and 8543 (84.98%) were obese adults. There were differences in the reporting of depressive symptoms in the underweight group; the most central items were “Depressed mood” (PH2), “Tiredness/low energy” (PH4), and “Psychomotor difficulties” (PH8). Conclusion: This study provides new evidence on the dynamic relationship between depressive symptoms according to the body mass index categories (underweight and obese) assessed.

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Polygenic risk for immuno-metabolic markers and specific depressive symptoms: A multi-sample network analysis study

Cited by 39 publications

References 88 publications

Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms

Circulating Inflammation Markers Partly Explain the Link Between the Dietary Inflammatory Index and Depressive Symptoms

Pathomechanisms of Vascular Depression in Older Adults

Network Analysis of Depressive Symptomatology in Underweight and Obese Adults

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