The Association Between Vascular Inflammation and Depressive Disorder. Causality, Biomarkers and Targeted Treatment

Kalkman, Hans O.

doi:10.3390/ph13050092

Cited by 18 publications

(16 citation statements)

References 200 publications

(244 reference statements)

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“…Furthermore, endothelial dysfunction was associated with a persistent course of depression [ 104 ]. More recent evidence for the role of systemic damage of the endothelium was found in a study showing that markers for endothelial dysfunction were associated with reduced CBF in LLD patients [ 101 , 105 ]. In conclusion, these studies suggest that macro- and microvascular dysfunctions causing impaired cerebral hemodynamics/reduced perfusion play a role in the development of LLD.…”

Section: Impaired Cerebral Hemodynamicsmentioning

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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Section: Impaired Cerebral Hemodynamicsmentioning

confidence: 99%

Pathomechanisms of Vascular Depression in Older Adults

Jellinger¹

2021

IJMS

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“…Recently, biomarkers of vascular inflammation have been implicated in the causation of depression. [36] Recently we have also reported the role of decreased NO in the development of CV risks in gestational hypertension. [37] Further, decreased brain NO synthase expression has been reported in depression.…”

Section: Dicussionmentioning

confidence: 94%

Sympathovagal imbalance, cardiometabolic risks and hypertension status are linked to depression in women having risk factors for pregnancy-induced hypertension

Pal

Habeebullah

Madhavan

et al. 2021

IJCEP

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Background and Aim: Pregnancy is a physiological state in which there are cardiovascular, autonomic, hemodynamic and psychological changes. Increase in incidence of stress and depression in antenatal period has been reported. Autonomic changes in pregnancy-induced hypertension (PIH) and its dysfunction in depression are well documented. However, there is no report of contribution of sympathovagal imbalance (SVI) and cardiometabolic alterations to stress and depression in PIH. Methods: In this case-control study, we assessed and analyzed cardiovascular autonomic functions including heart rate variability (HRV) and cardiometabolic risks (CMR) between pregnant women having risks of PIH (n=62) and normal healthy pregnant women (n=68). The perceived stress scale (PSS-10) and Quality of Life (QoL) were used to evaluate depressive symptoms and perceived stress. The HRV and CMR parameters were correlated with PSS. Multiple regression analysis was performed individually to study their association with PSS. Logistic regression was done to determine the prediction of hypertension/prehypertension status by PSS. Results: There was increase in heart rate and blood pressure, decreased HRV and increased markers of insulin resistance, atherogenic lipid profile, markers of inflammation, oxidative stress and vascular endothelial dysfunction in PIH risk subjects compared to control subjects. Parameters of SVI and decreased cardiovagal modulation and CMR were significantly correlated and associated with PSS. PSS had independent prediction of prehypertension/hypertension status in the study group. Conclusion: Findings of the present study indicate that there is considerable SVI and CMR in PIH. It appears that depression is the major cause of SVI and decreased cardiovagal modulation in PIH, and retrograde inflammation and vascular endothelial dysfunction could be the potential mechanisms of depression mediated SVI in PIH.

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“…2.1. Anti-Inflammatory Effects of EPA and DHA Several lines of evidence support an altered immune-status in depression, with proinflammatory cytokines in both plasma and cerebrospinal fluid influencing the progression and severity of depressive disorders [99][100][101][102][103][104][105][106][107]. While ω-3 PUFAs have been shown to reduce the secretion of pro-inflammatory cytokines in several cellular and animal models [108], there is also increasing support for a similar effect in humans.…”

Section: Omega-3 Pufas and Immunomodulationmentioning

confidence: 99%

Disentangling the Molecular Mechanisms of the Antidepressant Activity of Omega-3 Polyunsaturated Fatty Acid: A Comprehensive Review of the Literature

Kalkman

Hersberger

Walitza

et al. 2021

IJMS

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Major depressive disorders (MDDs) are often associated with a deficiency in long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), as well as signs of low-grade inflammation. Epidemiological and dietary studies suggest that a high intake of fish, the major source of ω-3 PUFAs, is associated with lower rates of MDDs. Meta-analyses of randomized placebo-controlled ω-3 PUFAs intervention-trials suggest that primarily eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), is responsible for the proposed antidepressant effect. In this review, we dissect the current biological knowledge on EPA and DHA and their bioactive lipid metabolites to search for a pharmacological explanation of this, to date, unexplained clinical observation. Through enzymatic conversion by cyclooxygenase (COX), lipoxygenase (ALOX), and cytochrome P-450 monooxygenase (CYP), EPA and DHA are metabolized to major anti-inflammatory and pro-resolving lipid mediators. In addition, both ω-3 PUFAs are precursors for endocannabinoids, with known effects on immunomodulation, neuroinflammation, food intake and mood. Finally, both ω-3 PUFAs are crucial for the structure and organization of membranes and lipid rafts. While most biological effects are shared by these two ω-3 PUFAs, some distinct features could be identified: (1) The preferential CYP monooxygenase pathway for EPA and EPA derived eicosanoids; (2) The high CB2 receptor affinities of EPA-derived EPEA and its epoxy-metabolite 17,18-EEQ-EA, while the DHA-derived endocannabinoids lack such receptor affinities; (3) The competition of EPA but not DHA with arachidonic acid (AA) for particular glycerophospholipids. EPA and AA are preferentially incorporated into phosphatidylinositols, while DHA is mainly incorporated into phosphatidyl-ethanolamine, -serine and -choline. We propose that these distinct features may explain the superior antidepressant activity of EPA rich ω-3 PUFAs and that these are potential novel targets for future antidepressant drugs.

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The Association Between Vascular Inflammation and Depressive Disorder. Causality, Biomarkers and Targeted Treatment

Cited by 18 publications

References 200 publications

Pathomechanisms of Vascular Depression in Older Adults

Pathomechanisms of Vascular Depression in Older Adults

Sympathovagal imbalance, cardiometabolic risks and hypertension status are linked to depression in women having risk factors for pregnancy-induced hypertension

Disentangling the Molecular Mechanisms of the Antidepressant Activity of Omega-3 Polyunsaturated Fatty Acid: A Comprehensive Review of the Literature

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