The role of the endocannabinoid system in the interplay of adverse childhood experiences and interleukin 6 in individuals with borderline personality disorder.
Jennifer Spohrs, Valentin Kühnle, Stefan O Reber, David Mikusky, Niklas Sanhüter, Ana Macchia, Sandra Nickel, Birgit Abler
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引用次数: 0
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.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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