Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation

TY - JOUR

T1 - Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation

AU - Funchal, Giselle A.

AU - Schuch, Jaqueline B.

AU - Zaparte, Aline

AU - Sanvicente-Vieira, Breno

AU - Viola, Thiago W.

AU - Grassi-Oliveira, Rodrigo

AU - Bauer, M. E.

N1 - Publisher Copyright: © 2023 Cambridge University Press. All rights reserved.

PY - 2024/4

Y1 - 2024/4

N2 - Background: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. Methods: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. Results: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. Conclusion: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

AB - Background: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. Methods: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. Results: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. Conclusion: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

KW - childhood maltreatment

KW - cocaine use disorder

KW - early life stress

KW - inflammation

KW - neutrophil extracellular traps

KW - phagocytosis

KW - smoked cocaine

KW - Reactive Oxygen Species/metabolism

KW - Cocaine/adverse effects

KW - Neutrophils/metabolism

KW - Cytokines

KW - Humans

KW - Inflammation/metabolism

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - Child Abuse

KW - Female

KW - Substance-Related Disorders

KW - Child

KW - Chronic Disease

U2 - 10.1017/neu.2023.11

DO - 10.1017/neu.2023.11

M3 - Journal article

C2 - 36847141

AN - SCOPUS:85149957067

SN - 0924-2708

VL - 36

SP - 97

EP - 108

JO - Acta Neuropsychiatrica

JF - Acta Neuropsychiatrica

IS - 2

ER -