Dercon, Q. | Search bioRxiv

bioRxiv2025

Inflammatory profiles of transdiagnostic symptom dimensions in healthy females

BackgroundPsychiatric disorders are increasingly conceptualised as heterogeneous categories with transdiagnostic underlying mechanisms that cut across multiple diagnoses and vary within a single diagnosis. Inflammation induced by psychosocial stress is one particularly potent example: previous research suggests that inflammatory profiles may correspond to symptom subgroups rather than traditional diagnostic categories. However, robust identification of transdiagnostic symptoms linked to specific inflammatory profiles remains rare. In this study, we examined the relationship between inflammatory profiles (at baseline and after a stress induction) and transdiagnostic symptom dimensions in females, who show higher prevalence of stress-related disorders such as anxiety and depression. MethodsA modest but relatively homogenous healthy female sample, between the ages of 18 and 35, was recruited (N=26). We obtained venous blood samples, at baseline and after a combined physiological and social stress induction, to measure full blood counts, plasma cytokines and peripheral blood mononuclear cells (PBMCs; for cell stimulation and intracellular flow cytometry analysis). Participants completed a battery of psychiatric self-report questions, from which we modelled three transdiagnostic factor scores. Finally, we used Bayesian regressions to evaluate the predictive contribution of transdiagnostic factors to inflammatory markers (at baseline and stress-induced), as well as to the principal components of inflammatory measures (derived from a principal component analysis (PCA) of the inflammatory data). ResultsWe identified specific relationships between inflammatory profiles and transdiagnostic symptom dimensions. Higher scores on a social withdrawal factor were associated with greater baseline neutrophil (95% highest density interval (HDI) = [0.06, 1.32]; BF10 = 2.92) and monocyte counts (95% HDI = [0.29, 1.46]; BF10 = 19.08), whereas higher anxious-depression scores were associated with a lower baseline monocyte count (95% HDI = [-0.96, -0.02]; BF10 = 1.81) and a greater inflammatory response to stress (e.g., change in neutrophil scores from pre- to post stress induction: (95% HDI = [0.18, 2.14]); BF10 = 5.66). We also found evidence for an association between the social withdrawal factor and an immune principal component most strongly weighted by monocytes, basophils, and IL-6 (95% HDI = [-1.14, -0.01]; BF10 = 1.88). ConclusionsWe find preliminary evidence that different transdiagnostic psychiatric symptom dimensions map onto specific inflammatory profiles, both at baseline and after a stress induction. This represents a proof-of-principle for the use of data-driven and hypothesis-driven approaches to identify and link transdiagnostic factors with inflammatory changes, which may be of use to future studies with larger, clinical populations, or for testing in the context of stratified interventions.

immunology↗

bioRxiv2025

Differential effects of dopamine and serotonin on reward and punishment processes in humans: A systematic review and meta-analysis

ImportanceTo support treatment assignment, mechanistic biomarkers should be selectively sensitive to specific interventions. Here, we examine whether different components of reinforcement learning in humans satisfy this necessary precondition. We focus on pharmacological manipulations of dopamine and serotonin that form the backbone of first-line management of common mental illnesses such as depression and anxiety. ObjectiveTo perform a meta-analysis of pharmacological manipulations of dopamine and serotonin and examine whether they show distinct associations with reinforcement learning components in humans. Data SourcesOvid MEDLINE/PubMed, Embase, and PsycInfo databases were searched for studies published between January 1, 1946 and January 19, 2023 (repeated April 9, 2024, and October 15, 2024) investigating dopaminergic or serotonergic effects on reward/punishment processes in humans, according to PRISMA guidelines. Study SelectionStudies reporting randomized, placebo-controlled, dopaminergic or serotonergic manipulations on a behavioral outcome from a reward/punishment processing task in healthy humans were included. Data Extraction and SynthesisStandardized mean difference (SMD) scores were calculated for the comparison between each drug (dopamine/serotonin) and placebo on a behavioral reward or punishment outcome and quantified in random-effects models for overall reward/punishment processes and four main subcategories. Study quality (Cochrane Collaborations tool), moderators, heterogeneity, and publication bias were also assessed. Main Outcome(s) and Measure(s)Performance on reward/punishment processing tasks. ResultsIn total, 68 dopamine and 39 serotonin studies in healthy volunteers were included (Ndopamine=2291, Nplacebo=2284; Nserotonin=1491, Nplacebo=1523). Dopamine was associated with an increase in overall reward (SMD=0.18, 95%CI [0.09 0.28]) but not punishment function (SMD=-0.06, 95%CI [-0.26,0.13]). Serotonin was not meaningfully associated with overall punishment (SMD=0.22, 95%CI [-0.04,0.49]) or reward (SMD=0.02, 95%CI [-0.33,0.36]). Importantly, dopaminergic and serotonergic manipulations had distinct associations with subcomponents. Dopamine was associated with reward learning/sensitivity (SMD=0.26, 95%CI [0.11,0.40]), reward discounting (SMD=-0.08, 95%CI [-0.14,-0.01]) and reward vigor (SMD=0.32, 95%CI [0.11,0.54]). By contrast, serotonin was associated with punishment learning/sensitivity (SMD=0.32, 95%CI [0.05,0.59]), reward discounting (SMD=-0.35, 95%CI [-0.67,-0.02]), and aversive Pavlovian processes (within-subject studies only; SMD=0.36, 95%CI [0.20,0.53]). Conclusions and RelevancePharmacological manipulations of both dopamine and serotonin have measurable associations with reinforcement learning in humans. The selective associations with different components suggests that reinforcement learning tasks could form the basis of selective, mechanistically interpretable biomarkers to support treatment assignment. Key pointsO_ST_ABSQuestionC_ST_ABSDo pharmacological manipulations of dopamine and serotonin affect components of reinforcement learning in humans? FindingsUpregulating dopamine is associated with increased reward learning/sensitivity and reward response vigor, and decreased reward discounting. Upregulation of serotonin is associated with increased punishment learning/sensitivity and decreased reward discounting. MeaningPharmacological manipulations of dopamine and serotonin have dissociable associations with different components of reinforcement learning. This forms a necessary basis for the development of selective markers for treatment assignment.

neuroscience↗