Abstract
AbstractBackgroundAdverse Childhood Experiences (ACEs) and Negative Life Events (NLEs) may activate immune-inflammatory pathways, which play a role in the onset of Major Depressive Disorder and its severe phenotype Major Dysmood disorder (MDMD).ObjectivesTo assess if elevated ACEs and NLEs in first episode (FE)-MDMD predict activation of the immune-inflammatory response system (IRS), chemokines, and growth factors that participate in the pathophysiology of MDMD.MethodsThis research assessed the effects of ACEs and NLEs on forty-eight cytokines/chemokines/growth factors, in 71 FE-MDMD patients and forty heathy controls.ResultsACEs are highly significantly associated with the classical M1 macrophage, T helper (Th)-1, Th-1 polarization, IRS, and neurotoxicity immune profiles, and not with the alternative M2, and Th-2 immune profiles. There are highly significant correlations between ACEs and NLEs and different cytokines/chemokines/growth factors, especially with interleukin (IL)-16, CCL27, stem cell growth factor, and platelet-derived growth factor. Partial Least Squares analysis showed that 62.3% of the variance in the depression phenome (based on severity of depression, anxiety and suicidal behaviors) was explained by the regression on IL-4 (p=0.001, inversely), the sum of ACEs + NLEs (p<0.0001), and a vector extracted from 10 cytokines/chemokines/growth factors (p<0.0001; both positively associated). The latter partially mediated (p<0.0001) the effects of ACE + NLEs on the depression phenome.ConclusionsPart of the effects of ACEs and NLEs on the depression phenome is mediated via activation of immune and growth factor networks. These pathways have a stronger impact in subjects with lowered activities of the compensatory immune-regulatory system.
Publisher
Cold Spring Harbor Laboratory