Shared metabolic and neuroimmune mechanisms underlying Type 2 Diabetes Mellitus and Major Depressive Disorder

Duarte-Silva, Eduardo; Melo, M. T. de; Maes, Michaël; Filho, Adriano José Maia Chaves; Macêdo, Danielle Silveira; Peixoto, Christina Alves

doi:10.1016/j.pnpbp.2021.110351

Cited by 29 publications

(27 citation statements)

References 174 publications

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Section: Metabolic Disordersmentioning

confidence: 99%

“…MDD patients often have metabolic disorders, and patients with metabolic disorders also tend to have depressive symptoms [88][89][90]. In recent years, it has been noted that systemic chronic inflammation is associated with intestinal mucosal barrier dysfunction, and partly involved in the development of obesity and type 2 diabetes [90,91]. As discussed in Section 2.3, systemic inflammation is considered a pathogenesis of MDD, hence metabolic diseases and MDD may share pathological mechanism commonalities.…”

Section: Metabolic Disordersmentioning

confidence: 99%

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How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Suda

Matsuda

2022

IJMS

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Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut–brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known to contribute to the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, which could affect neuronal development and synaptic plasticity. Increased gut permeability causes an influx of gut microbial components such as lipopolysaccharides, and the resultant systemic inflammation may lead to neuroinflammation in the central nervous system. In light of the fact that gut microbial factors contribute to the initiation and exacerbation of depressive symptoms, this review summarizes the current understanding of the molecular mechanisms involved in MDD onset, and discusses the therapeutic potential of probiotics, including butyrate-producing bacteria, which can mediate the microbiota–gut–brain axis.

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Section: Metabolic Disordersmentioning

confidence: 99%

Section: Metabolic Disordersmentioning

confidence: 99%

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Suda

Matsuda

2022

IJMS

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“…There is a significant comorbidity between mood disorders including major depressive and bipolar disorder and T2DM and MetS-associated features, including atherogenicity and IR [6][7][8][9][10][11]. According to the WHO (2017), T2DM is frequently accompanied by mood disorders and a systematic review and meta-analysis showed that the prevalence of depression in T2DM is around 25% [12].…”

Section: Introductionmentioning

confidence: 99%

“…The comorbidity between mood disorders (either MDD or BD) and T2DM may be explained by multiple overlapping pathways, including IR, atherogenicity, activation of immune-inflammatory and nitro-oxidative stress pathways, an acute phase response, complement activation, T helper (Th)-17 activation, lowered antioxidant levels, mitochondrial dysfunction, and breakdown of the blood-brain-barrier (BBB) and the gut tight junctions barriers (leaky BBB and gut) [11]. Moreover, lowered plasma albumin, an inflammatory marker, predicts T2DM [15] and is a hallmark of MDD [16].…”

Section: Introductionmentioning

confidence: 99%

“…The same shared pathways underpin the comorbidity between mood disorders and MetS [17][18][19][20][21]. Shared biomarkers of mood disorders, T2DM, and MetS comprise increased levels of pro-inflammatory cytokines, malondialdehyde (MDA, indicating lipid peroxidation), nitric oxide (NO) metabolites (indicating increased NO production), and advanced protein oxidation products (AOPPs), and lowered paraoxonase (PON)-1 activity [10,11,22,23]. Nevertheless, the biomarkers of affective symptoms (depression and anxiety) in T2DM are not well established and, consequently, research should focus on the up-or downstream biomarkers of the abovementioned pathways that play a role in depression and anxiety due to T2DM.…”

Section: Introductionmentioning

confidence: 99%

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Intersections between Copper, β-Arrestin-1, Calcium, FBXW7, CD17, Insulin Resistance and Atherogenicity Mediate Depression and Anxiety Due to Type 2 Diabetes Mellitus: A Nomothetic Network Approach

Al‐Hakeim

Hadi

Jawad

et al. 2022

JPM

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Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established. The present study delineated the effects of serum levels of copper, zinc, β-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, calcium, magnesium on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls beyond the effects of insulin resistance (IR) and atherogenicity. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales. We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, β-arrestin-1, calcium, and IR coupled with atherogenicity. Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms, which were mediated by IR and atherogenicity. Copper, β-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of IR and atherogenicity. T2DM and affective symptoms share common pathways, namely increased atherogenicity, IR, copper, and β-arrestin-1, and lowered calcium, whereas copper, β-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.

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The molecular pathophysiology of depression and the new therapeutics

Tian

et al. 2022

MedComm

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Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long‐lasting antidepressant effects in treatment‐resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects.

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Shared metabolic and neuroimmune mechanisms underlying Type 2 Diabetes Mellitus and Major Depressive Disorder

Cited by 29 publications

References 174 publications

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Intersections between Copper, β-Arrestin-1, Calcium, FBXW7, CD17, Insulin Resistance and Atherogenicity Mediate Depression and Anxiety Due to Type 2 Diabetes Mellitus: A Nomothetic Network Approach

The molecular pathophysiology of depression and the new therapeutics

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