Inflammation, childhood trauma, and symptom dimensions in schizophrenia: a path-analysis study

Abstract

Introduction: It has been postulated that immune dysregulations may establish a link between early risk factors, such as childhood trauma (CT), and the later development of schizophrenia. Schizophrenia and experience of childhood trauma (CT) have independently been associated with increased circulating levels of inflammatory biomarkers, while CT and inflammation have also been linked to particular clinical features of the disorder. We investigated whether increased levels of inflammatory biomarkers were underpinned by CT among subjects with schizophrenia, and whether this inflammation mediated the relationship between CT and symptom dimensions.

Methods: 451 subjects from the FACE-SZ ("FondaMental Academic Centres of Expertise for Schizophrenia") cohort were included. Path-analysis was used to evaluate direct and indirect relationships between Childhood Trauma Questionnaire (CTQ) scores, serum concentrations of C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, and Positive And Negative Syndrome Scale of Schizophrenia (PANSS) scales.

Results: Significant associations between CTQ and PANSS scales and between the former and inflammatory biomarkers were found. Notably, CRP was positively predicted by emotional abuse (β = 0.10) and physical neglect (β = 0.12), and negatively by emotional neglect while IL-6 (β = -0.18) was negatively predicted by sexual abuse (β = -0.05). No indirect associations between CT on PANSS through effects on the inflammatory biomarkers were found.

Conclusions: Our study confirmed the association between CT and PANSS dimensions and identified novel links between CT and inflammation among patients with schizophrenia, highlighting the need for further elucidation of the complex relationships between early stress and chronic inflammation in psychiatry.

Keywords: Biomarkers; Childhood trauma; Cytokines; Inflammation; Schizophrenia.

Fig. 1

Path-analysis diagram modelling the relationships between CT types, selected peripheral inflammatory biomarkers, and PANSS factors. Legends: Arrows imply significant associations (p-value<0.05); the colour blue represents correlations, while red and orange arrows (paths) depict direct and indirect effects, respectively; the given values correspond to the standardised regression coefficients for each path Abbreviations: Dep: depressed PANSS factor, Dis.: disorganised PANSS factor, EA: emotional abuse, EN: emotional neglect, Exc.: excited PANSS factor, Neg.: negative PANSS factor, PA: physical PANSS abuse, PN: physical neglect, Pos.: positive PANSS factor, SA: sexual abuse.