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Background: Heroin and other opioid use disorders (HUD and OUD) cause major public health morbidity and mortality. Although standard-of-care medication assisted treatment (MAT) exists, little is known about potential predictors of change during recovery. Recovery can include normalization of brain white matter (WM) microstructure, which is sensitive to cytokine and immune signaling. Here we aimed to determine whether blood-based serum cytokine/immune levels can be markers of WM microstructure recovery following MAT. Methods: Inpatient Individuals with HUD (iHUD; n=21) and healthy controls (HC; n=24) underwent magnetic resonance scans with diffusion tensor imaging (DTI) and provided ratings of drug cue-induced craving, arousal and valence twice, earlier in treatment and ≈14 weeks of inpatient MAT (with methadone or buprenorphine) thereafter. At this second session (MRI2), they also provided a peripheral blood sample for multiplex relative quantification of serum cytokine/immune proteins (with a proximity extension assay, Olink). We explored the correlation of a multi-target cytokine biomarker score (based on principal component analysis of 19 proteins that differed significantly between iHUD and HC) with change in whole-brain DTI (ΔDTI; MRI2 - MRI1) metrics (fractional anisotropy, mean diffusivity, and axial diffusivity) across the 14 weeks of MAT. Results: The cytokine biomarker score, obtained at the MRI2 stage, was correlated with ΔDTI metrics in frontal, fronto-parietal, and cortico-limbic WM tracts (e.g., including the genu of the corpus callosum, anterior corona radiata, and others). In a follow-up analysis, specific cytokines represented in the multi-target biomarker score, such as the interleukin-related oncostatin M (OSM), colony-stimulating factor (CSF1), and the chemokine CCL7 were correlated with similar ΔDTI metrics in iHUD, but not in HC. Levels of other specific cytokines (i.e., CCL19 and CCL2) were negatively correlated with change in cue-induced craving or arousal. Thus, lower levels of the aforementioned cytokines were correlated with an increase in cue-induced craving or arousal across the two stages (MRI2 - MRI1). Conclusions: Studied as a multi-target biomarker score, or as selected individual targets, peripheral serum cytokines are highly accessible biomarkers of WM microstructure recovery in iHUD undergoing inpatient MAT.
Background: Heroin and other opioid use disorders (HUD and OUD) cause major public health morbidity and mortality. Although standard-of-care medication assisted treatment (MAT) exists, little is known about potential predictors of change during recovery. Recovery can include normalization of brain white matter (WM) microstructure, which is sensitive to cytokine and immune signaling. Here we aimed to determine whether blood-based serum cytokine/immune levels can be markers of WM microstructure recovery following MAT. Methods: Inpatient Individuals with HUD (iHUD; n=21) and healthy controls (HC; n=24) underwent magnetic resonance scans with diffusion tensor imaging (DTI) and provided ratings of drug cue-induced craving, arousal and valence twice, earlier in treatment and ≈14 weeks of inpatient MAT (with methadone or buprenorphine) thereafter. At this second session (MRI2), they also provided a peripheral blood sample for multiplex relative quantification of serum cytokine/immune proteins (with a proximity extension assay, Olink). We explored the correlation of a multi-target cytokine biomarker score (based on principal component analysis of 19 proteins that differed significantly between iHUD and HC) with change in whole-brain DTI (ΔDTI; MRI2 - MRI1) metrics (fractional anisotropy, mean diffusivity, and axial diffusivity) across the 14 weeks of MAT. Results: The cytokine biomarker score, obtained at the MRI2 stage, was correlated with ΔDTI metrics in frontal, fronto-parietal, and cortico-limbic WM tracts (e.g., including the genu of the corpus callosum, anterior corona radiata, and others). In a follow-up analysis, specific cytokines represented in the multi-target biomarker score, such as the interleukin-related oncostatin M (OSM), colony-stimulating factor (CSF1), and the chemokine CCL7 were correlated with similar ΔDTI metrics in iHUD, but not in HC. Levels of other specific cytokines (i.e., CCL19 and CCL2) were negatively correlated with change in cue-induced craving or arousal. Thus, lower levels of the aforementioned cytokines were correlated with an increase in cue-induced craving or arousal across the two stages (MRI2 - MRI1). Conclusions: Studied as a multi-target biomarker score, or as selected individual targets, peripheral serum cytokines are highly accessible biomarkers of WM microstructure recovery in iHUD undergoing inpatient MAT.
ObjectivesTo assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation and sick leave.MethodsUsing the French health insurance database, this nationwide cohort study included adults with PsA who were new users (not in the year before the index date) of targeted therapies for ≥9 months during 2015–2021. Main endpoints were difference in proportion of users of associated treatments, hospitalisations and sick leaves between 3 and 9 months after and 6 months before targeted therapy initiation. Logistic regression models adjusted for sex, age, psoriasis, inflammatory bowel disease and Charlson Comorbidity Index compared the impact of biologics initiation (tumour necrosis factor inhibitor (TNFi)/interleukin 17 inhibitor (IL17i)/IL12/23i) on associated treatment discontinuation.ResultsAmong 9793 patients initiating targeted therapy for PsA (mean age: 51±13 years, 47% men), 62% initiated TNFi, 14% IL17i, 10% IL12/23i, 1% Janus kinase inhibitor, 12% phosphodiesterase-4 inhibitor. After treatment initiation, the proportion of treatment users was significantly reduced for NSAIDs (−15%), opioid analgesics (−9%), prednisone (−9%), methotrexate (−15%) and mood disorder treatments (−2%), along with decreased hospitalisations (−12%) and sick leaves (−4%). TNFi had a greater sparing effect on NSAIDs and prednisone use than IL17i (ORa=1.04, 95% CI=1.01 to 1.07; 1.04, 1.02 to 1.06) and IL12/23i (1.07, 1.04 to 1.10; 1.06, 1.04 to 1.09). Odds of methotrexate discontinuation was reduced with TNFi versus IL17i (0.96, 0.94 to 0.98) and IL12/23i (0.94, 0.92 to 0.97).ConclusionsTargeted therapy initiation for PsA reduced the use of associated treatment and healthcare, with TNFi having a slightly greater effect than IL17i and IL12/23i, except for methotrexate discontinuation.
Opioid Use Disorder is a chronic condition characterized by compulsive opioid use despite negative consequences, resulting in severe health risks such as overdose and contraction of infectious diseases. High dropout rates in opioid agonist therapy highlight the need for more effective relapse prevention strategies. Animal and clinical studies indicate that opioids influence gut microbiota, which in turn plays a critical role in addiction development and alters behavioral responses to opioids. This study provides a comprehensive review of the literature on the effects of opioids on the gut microbiome and explores the potential of microbiome manipulation as a therapeutic target in opioid addiction.
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