The effects of adverse childhood experiences on depression and suicidal behaviors are partially mediated by neuroticism, a forme fruste of major depression

Abstract

Neuroticism, a personality trait, can predict major depressive disorder (MDD). The current study aims to determine whether a) neuroticism is a feature of the acute state of MDD, including suicidal behaviors (SB); and b) adverse childhood experiences (ACEs) are associated with neuroticism in MDD. This study included 133 participants, 67 normal controls and 66 MDD patients, and assessed the Big 5 Inventory (BFI), ACEs using the ACE Questionnaire, and the phenome of depression using the Hamilton Depression (HAMD) Rating Scale (HAMD), Beck Depression Inventory (BDI), State-Trait Anxiety (STAI) and Columbia Suicide Severity Rating Scale (C-SSRS) scores to assess current SB. Neuroticism was significantly higher in MDD than controls, and it explained 64.9% of the variance in the depression phenome (a latent vector extracted from HAMD, BDI, STAI, and current SB scores). The other BFI domains had much less (extraversion, agreeableness) or no effect (openness, conscientiousness). One latent vector could be extracted from the phenome, lifetime dysthymia, lifetime anxiety disorders and neuroticism scores. Neglect (physical and emotional) and abuse (physical, neglect and sexual) account for approximately 30% of the variance in this latent vector. Partial Least Squares analysis showed that the effects of neglect on the phenome were partially mediated by neuroticism, whereas the effects of abuse were completely mediated by neuroticism. Neuroticism (trait) and the MDD phenome (state) are both manifestations of the same latent core, with neuroticism being a less severe manifestation of major depression, which in fact is a multiplicative manifestation of neuroticism.

Towards a major methodological shift in depression research by assessing continuous scores of recurrence of illness, lifetime and current suicidal behaviors and phenome features: focus on atherogenicity and adverse childhood experiences

“…We [14] used principal component analysis (PCA) to determine three important ACE categories: a) using ACE9, ACE10, ACE11, ACE12, ACE13, and ACE15 (physical and emotional neglect items, for a full list and description of the ACE components, see Table 1 in the Electronic Supplementary File in [14]), we created a PC that we named “ACEneglect”; b) using ACE1, ACE2, ACE3, ACE4, ACE19, ACE20, ACE21, and ACE22 (all physical and emotional abuse ACE items), we derived a second validated factor, named “ACEabuse” [14]; and c) using ACE5, ACE6, ACE7, and ACE8 (all sexual abuse items) we constructed a third PC, labeled ACEsexabuse [14]. The other ACE rating scale items were not significant in the current analysis.…”

“…Seven items from the C-SSRS were used to derive the first PC reflecting current (last month) suicidal ideation (Current_SI, KMO=0.703, Bartlett’s χ 2 =982.510, df=15, p<0.001, EV=72.05%, all loadings > 0.672; [14]). The severity of current SA (Current_SA) was calculated using the first PC extracted from 5 C-SSRS items [14] (KMO=0.636, Bartlett’s χ2=302.236, df=3, p<0.001, EV=81.14%, all loadings > 0.807). Current SBs (Current_SBs) were conceived of as a z-unit-weighted composite of Current_SI and Current_SA.…”

“…In addition, no discriminant validity could be established between ROI and depressive traits, suggesting that both facets are manifestations of the same core, namely the lifetime+Current phenome of depression. These findings are highly significant since they demonstrate that neuroticism and dysthymia are mild variants of the disease “depression” [2, 14]. As previously mentioned, neuroticism and dysthymia can be viewed as prodromes or residual symptoms following an acute episode [14].…”

“…Neuroticism was measured using a Thai version of the Big Five Inventory [28, 29]. Since neuroticism is the sole factor consistently linked to MDD, we used raw scores from that dimension in the current study [14]. Both the Beck Depression Inventory II (BDI-II) [30] and the Hamilton Rating Scale for Depression [31] were used to assess depressive symptoms.…”

“…The proper approach to defining a “correct outcome model” of depression research is to employ continuous variables reflecting a) the current phenome, comprising current suicidal behaviors (SBs), the severity of illness as assessed with depression interview-based ratings scales, and self-rated scales assessing depression, health-related quality of life (HR-QoL) and disabilities [1,2,5,7,10], and b) the lifetime phenome, which comprises ROI and different traits [13], including neuroticism, a form fruste of depression, dysthymia and anxiety disorders, such as generalized anxiety disorder (GAD) [5,7,13,14]. Genetic and trait biomarkers should consequently be used as predictors in ML techniques to predict the correct outcome model of depression, and state biomarkers should be used to examine associations with current phenome data.…”