The interplay between sexual abuse and inflammation, oxidative stress, and DNA damage in drug-naïve panic disorder patients

• Published in: Molecular psychiatry Vol. 28; no. 7; pp. 2995 - 3001
• Main Authors: Quagliato, Laiana A., Nardi, Antonio E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2023; Nature Publishing Group
• Subjects: 631/45; 692/53/2421; 8-Hydroxy-2'-Deoxyguanosine; 96/21; Anxiety; Behavioral Sciences; Biological Psychology; Biomarkers; Child; Child abuse & neglect; Children; Clinical trials; Deoxyguanosine; DNA Damage; Humans; IL-1β; Immunosuppressive agents; Inflammasomes; Inflammation; Interleukin 1; Medicine; Medicine & Public Health; Mental disorders; Neurosciences; Oxidative stress; Oxidative Stress - physiology; Panic attacks; Panic Disorder; Pharmacotherapy; Psychiatry; Sex crimes; Sex Offenses; Sexual abuse; Thiobarbituric Acid Reactive Substances; Trauma
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-023-02086-z

Although accumulating evidence suggests an interplay between child abuse and inflammatory processes and the pathophysiology of mental disorders, few studies have investigated the cellular mechanisms related to this matter. Furthermore, no studies to date have evaluated cytokine, oxidative stress, and DNA damage levels in drug-naïve panic disorder (PD) patients and their possible association with childhood trauma. The aim of the present study was to determine the levels of the proinflammatory interleukin (IL)-1B, the oxidative stress marker TBARS, and  8-hydroxy-2' -deoxyguanosine (8-OHdG; representing DNA damage) in drug-naïve PD patients compared to controls. Furthermore, this investigation aimed to determine whether early-life trauma could predict peripheral levels of the previously mentioned markers in unmedicated PD patients. This work showed that drug-naïve PD patients presented elevated levels of TBARS and IL-1B but not 8-OHdG compared to healthy controls. In addition, sexual abuse during childhood was associated with increased levels of IL-1B in PD patients. Our findings suggest that the microglial NLRP3 inflammasome complex might be activated in drug-naïve PD patients. This study is the first to associated sexual abuse with increased levels of IL-1B in drug-naïve PD patients and to demonstrate that this population presents high concentrations of oxidative stress and inflammation markers but not DNA damage markers when compared to healthy controls. Independent replication of these findings would support further clinical trials of inflammasome inhibitory drugs in PD patients, which could lead to effective novel treatments for people with PD and contribute to elucidating pathophysiological differences depending on trauma exposure in the immune disturbances accompanying PD.