The role of the endocannabinoid system in the interplay of adverse childhood experiences and interleukin 6 in individuals with borderline personality disorder
Psychopharmacology (Berl). 2025 May 17. doi: 10.1007/s00213-025-06809-8. Online ahead of print.
ABSTRACT
RATIONALE: Adverse childhood experiences (ACEs) have been identified as a major risk factor for psychiatric disorders from childhood to adult life along with the dysregulation of neuroendocrinological processes mediating stress and inflammation. The endocannabinoid system (ECS) has been found to play a putative role in the release of inflammatory cytokines.
OBJECTIVE: We investigated the role of the ECS in the interplay between ACEs and interleukin 6 (IL-6) as an inflammatory marker.
METHODS: We analysed ACEs (CTQ, Bernstein et al. 2003), plasma IL-6 and endocannabinoid concentrations (anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in a cohort comprising 48 female individuals diagnosed with borderline personality disorder (BPD) and 31 matched healthy controls (HCs).
RESULTS: We found higher IL-6 levels in individuals with BPD compared to HCs and, across all study participants, observed significant positive correlations between AEA, 2-AG and IL-6 levels. CTQ sum scores correlated positively with IL-6 concentrations at a trend level (statistically significant for sexual abuse). Correlations between CTQ sum scores and IL-6 levels were particularly strong in participants with low endocannabinoid levels (lowest three quartiles; n = 57) while in the quartile with the highest endocannabinoid levels (n = 19), no correlations were evident. Furthermore, an exploratory analysis applying a median split for IL-6 levels revealed that the number of individuals with recent suicide attempts (< 1 month ago) was significantly higher in the high IL-6 levels group (OR = 0.22; 95%CI = 0.06-0.86).
CONCLUSION: Our findings support the bidirectional link between ACEs and immune system alterations and suggest that endocannabinoids may counteract the stress-inflammatory response.
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