Are abnormalities in lipid metabolism, together with adverse childhood experiences, the silent causes of immune-linked neurotoxicity in major depression?

Abstract Background Severe or recurring major depression is associated with increased adverse childhood experiences (ACEs), heightened atherogenicity, and immune-linked neurotoxicity (INT). Nevertheless, the interconnections among these variables in outpatient of major depression (OMDD) have yet to be determined. Objectives Determine the correlations among INT, atherogenicity, and ACEs in 66 OMDD patients (of whom thirty-three had metabolic syndrome, MetS) and sixty-seven controls (31 of whom had MetS). Results The free cholesterol/reverse cholesterol transport ratio, apolipoprotein (Apo) B and E, and a comprehensive atherogenicity index were all significantly associated with increased INT in OMDD subjects without MetS. ACEs were substantially correlated with INT in patients with MetS. INT (only in MetS) and atherogenicity indices (only in people without MetS) were significantly associated with the clinical phenome features of OMDD, including the recurrence of illness (ROI, including lifetime suicidal behaviors), the lifetime phenome (neuroticism + lifetime anxiety disorders and dysthymia), and the current phenome (including current suicidal behaviors). A significant proportion of the variability (58.3%) in the lifetime + current phenome could be accounted for by INT, interactions between INT and atherogenicity (labeled "atherommune index"), ApoE, three ACE subtypes (all positively correlated), and age (inversely correlated). A single validated latent construct could be extracted from ROI, lifetime phenome, current phenome, INT, and atherommune index. 36.1% of this factor’s variance was accounted for by three ACE subtypes. Discussion We have developed a novel OMDD model, namely a pathway phenotype, labeled the "atherommune-phenome," which demonstrates that the interplay between INT and atherogenicity is essential to OMDD.