Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome.

The pathophysiology of amnestic Mild Cognitive Impairment (aMCI) is largely unknown, although some papers found signs of immune activation. To assess the cytokine network in aMCI after excluding patients with major depression (MDD) and to examine the immune profiles of quantitative aMCI (qMCI) and distress symptoms of old age (DSOA) scores. A case-control study was conducted on 61 Thai aMCI participants and 60 healthy old adults (both without MDD). The Bio-Plex Pro human cytokine 27-plex test kit was used to assay cytokines/chemokines/growth factors in fasting plasma samples. aMCI is characterized by a significant immunosuppression, and reductions in T helper 1 (Th)1 and T cell growth profiles, the immune-inflammatory responses system, interleukin (IL)1β, IL6, IL7, IL12p70, IL13, GM-CSF, and MCP-1. These 7 cytokines/chemokines exhibit neuroprotective effects at physiologic concentrations. In multivariate analyses, three neurotoxic chemokines, CCL11, CCL5, and CXCL8, emerged as significant predictors of aMCI. Logistic regression showed that aMCI was best predicted by combining IL7, IL1β, MCP-1, years of education (all inversely associated) and CCL5 (positively associated). We found that 38.2% of the variance in the qMCI score was explained by IL7, IL1β, MCP-1, IL13, years of education (inversely associated) and CCL5 (positively associated). The DSOA was not associated with any immune data. An imbalance between lowered levels of neuroprotective cytokines and chemokines, and relative increases in neurotoxic chemokines are key factors in aMCI. Future MCI research should always control for the confounding effects of affective symptoms. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-73099-z.

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Disorders in lipid metabolism, oxidative stress, and antioxidants in patients with amnestic mild cognitive impairment without major depression

Nantachai,

Maes,

Tran-Chi

et al. 2024

Preprint

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BackgroundAmnestic mild cognitive impairment (aMCI) is characterized by changes in lipids and oxidative stress (OS). It is crucial to exclude patients with major depression (MDD) to accurately evaluate these biomarkers in aMCI.AimsTo examine lipid and oxidative stress biomarkers associated with aMCI versus normal controls.MethodsWe performed a case-control analysis involving 61 individuals with aMCI (without MDD) and 60 healthy controls. We assessed the severity of aMCI, distress symptoms of old age, and lipid/OS biomarkers.ResultsThe levels of serum -SH groups were significantly higher in individuals with aMCI, while the levels of malondialdehyde (MDA) were significantly lower in the same group. Serum advanced oxidation protein products, glutathione, and folic acid did not show any notable variations. In individuals with aMCI, we observed an elevated apolipoprotein B (ApoB)/ApoA ratio, as well as decreased levels of high-density lipoprotein cholesterol (HDL), ApoA, and a reverse cholesterol transport (RCT) index. The simultaneous presence of aMCI and subclinical depressive symptoms is marked by elevated levels of triglycerides and ApoB, as well as decreased levels of ApoA and HDL. A significant portion of the variability (24.9%) in a quantitative MCI severity score can be attributed to -SH groups, age (positively), MDA and education (inversely).DiscussionThe alterations in MDA and -SH levels in aMCI may potentially disrupt redox signaling, which can affect cell signaling and homeostatic setpoints. The interaction between aMCI and subclinical depressive symptoms can lead to increased atherogenicity and reduced antiatherogenic protection.

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Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome.

Cited by 3 publications

References 59 publications

The recurrence of illness (ROI) index is a key factor in major depression that indicates increasing immune-linked neurotoxicity and vulnerability to suicidal behaviors

The recurrence of illness (ROI) index is a key factor in major depression that indicates increasing immune-linked neurotoxicity and vulnerability to suicidal behaviors

Cytokine dysregulation in amnestic mild cognitive impairment

Disorders in lipid metabolism, oxidative stress, and antioxidants in patients with amnestic mild cognitive impairment without major depression

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