Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder

Massardo, Teresa; Quintana, Juan Carlos López; Jaimovich, Rodrigo; Sáez, Claudia G.; Risco, Luis; Liberman, Claudio; Araya, A. Verónica; Galleguillos, Tamara; Castro-Mora, Gabriel; Pereira, Jaime

doi:10.1159/000508110

Cited by 14 publications

(12 citation statements)

References 64 publications

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“…Sertraline has been found to lessen increased platelet secretion found among depressed patients; however, both groups of our patients were receiving SSRIs [79]. Endothelial dysfunction is also consistently present in MDD, as well as platelet activation and other peripheral inflammatory and oxidative stress biomarkers associated to rCBF changes after SSRIs therapy, as demonstrated by our group [80, 81].…”

Section: Discussion/conclusionsupporting

confidence: 62%

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

et al. 2022

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Introduction: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. Methods: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck’s Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. Results: Clinical scores decreased in both groups (p = 0.0001); Beck’s presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. Conclusion: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.

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Section: Discussion/conclusionsupporting

confidence: 62%

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

et al. 2022

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“…Such biomarkers of endothelial dysfunction include endothelin-1 (ET-1), circulating endothelial cells, endothelial microparticles, endoglin, etc. [ 100 ], plasma soluble intercellular adhesion molecules (siCAM), or high-sensitive C-reactive particles (hs-CRP) [ 101 ]. A genome-wide association study (GWAS) suggested a potential role of vascular endothelial growth factor (VEGF) in depression development [ 102 ].…”

Section: Impaired Cerebral Hemodynamicsmentioning

confidence: 99%

“…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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“…Additionally, perfusion abnormality in BA 23 increased in both groups but more in the placebo group. In one of our previous studies published recently, a significant association between endothelial dysfunction markers and changes in rCBF was observed in another group of MDD patients not taking any specific medication [76]. This suggests that the systematic damage or activation of the endothelium may be contributing to the observed perfusion abnormality.…”

Section: Feature Selectionmentioning

confidence: 68%

Identification of Statin’s Action in a Small Cohort of Patients with Major Depression

et al. 2021

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Statins are widely used as an effective therapy for ischemic vascular disorders and employed for primary and secondary prevention in cardiac and cerebrovascular diseases. Their hemostatic mechanism has also been shown to induce changes in cerebral blood flow that may result in neurocognitive improvement in subjects with Major Depressive Disorder. Behavioral data, various blood tests, and resting-state brain perfusion data were obtained at the start of this study and three months post-therapy from a small cohort of participants diagnosed with Major Depressive Disorder. Subjects received either rosuvastatin (10 mg) or placebo with their standard selective serotonin reuptake inhibitors therapy. At the end of the study, patients using rosuvastatin reported more positive mood changes than placebo users. However, standard statistical tests revealed no significant differences in any non-behavioral variables before and after the study. In contrast, feature selection techniques allowed identifying a small set of variables that may be affected by statin use and contribute to mood improvement. Classification models built to assess the distinguishability between the two groups showed an accuracy higher than 85% using only five selected features: two peripheral platelet activation markers, perfusion abnormality in the left inferior temporal gyrus, Attention Switching Task Reaction latency, and serum phosphorus levels. Thus, using machine learning tools, we could identify factors that may be causing self-reported mood improvement in patients due to statin use, possibly suggesting a regulatory role of statins in the pathogenesis of clinical depression.

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Regional Brain Perfusion Is Associated with Endothelial Dysfunction Markers in Major Depressive Disorder

Cited by 14 publications

References 64 publications

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder

Pathomechanisms of Vascular Depression in Older Adults

Identification of Statin’s Action in a Small Cohort of Patients with Major Depression

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