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Major depression, suicidal behaviors and neuroticism are pro-atherogenic states driven by lowered reverse cholesterol transport.

Jirakran, K.; Vasupanrajit, A.; Tunvirachaisakul, C.; Kubera, M.; Maes, M.

2023-02-11 psychiatry and clinical psychology
10.1101/2023.02.10.23285746 medRxiv
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BackgroundThere are strong associations between major depressive disorder (MDD), metabolic syndrome (MetS) and cardiovascular disorder, which may be explained by increased atherogenicity and the microimmuneoxysome (Maes et al., 1994; 2011). The present study was conducted to determine if MDD, the severity of depression, suicidal behaviors, and neuroticism are associated with increased pro-atherogenic versus anti-atherogenic indices (PRO/ANTI-AI) and a reverse cholesterol transport (RCT) index. MethodsThis study included 34 healthy controls, 33 participants with MetS, and MDD patients with (n=31) and without (n=35) MetS, and measured total (TC) and free (FC) cholesterol, high (HDLc) and low (LDLc) density lipoprotein cholesterol, triglycerides (TG), apolipoprotein (ApoA), ApoB, cholesterol esterification rate (CER) and a composite (based on HDLc, ApoA and CER), reflecting RCT. ResultsIn the combined MDD + MetS study group, no associations between MDD and lipids were detected. After the exclusion of all MetS participants, MDD is strongly associated with (a) increased FC, TG, ApoB, Castelli risk index 1, ApoB/ApoA, and (b) decreased HDLc, ApoA and the RCT index. In participants without MetS, there are significant associations between severity of depression, suicidal behaviors, and neuroticism and ApoB/ApoA, Castelli risk, and RCT indices. ConclusionsStudies linking lipids to depressive subtypes can only be interpreted after MetS patients are excluded. The depression phenome, suicidal behaviors, and neuroticism are associated with a lowered RCT and increased atherogenicity, which are likely involved in the microimmuneoxidative pathophysiology of MDD. The RCT is a new drug target to treat and prevent MDD, neuroticism, and suicidal behaviors.

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