Neuro-Immuno-Endocrine Interactions in Early Life Stress and Heroin Withdrawal Timeline

Both heroin abuse and early life stress (ELS) affect the immune system and the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, accelerated aging due to mild inflammation has been indicated in these conditions. The present study aims to compare plasma levels of apoptosis markers, inflammatory markers, and stress hormones during early heroin abstinence period. Thirty-one individuals with heroin/opioid use disorder who had heroin-ELS and 26 of their siblings who were not abusing substances (ELS), and 32 individuals with heroin/opioid use disorder without a history of ELS (heroin-no ELS) were included in the study. The levels of interleukin-6, C-reactive protein, erythrocyte sedimentation rate, albumin, alanine transaminase, aspartate transaminase, and white blood cell count were assessed as the inflammatory and biochemistry markers. Also, apoptosis markers including tumor necrosis factor (TNF)-related weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, soluble tumor necrosis factor receptor type I as apoptosis markers were detected by enzyme-linked immunosorbent assay. ELS was simultaneously evaluated using the Childhood Trauma Questionnaire, Minnesota Multiphasic Personality Inventory, and beck depression inventory scales. Besides, heroin craving was assessed by Daily Drinking/Drug Questionnaire score in individuals with heroin use disorder. This is the first study to evaluate the inflammatory, stress, and apoptosis markers during heroin abstinence, supporting the association between ELS and peripheral pro-inflammatory markers' levels and HPA axis.