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Major depressive disorder (MDD) is associated with dysfunctional self-reported interoception (i.e., abnormal perception of the body's physiological state) and systemic inflammation, both of which adversely affect treatment response. In this study, we explored associations between C-reactive protein (CRP) and self-reported interoception, to gain more insight into the pathophysiology of interoceptive impairments in MDD. We also aimed to replicate previous findings on the associations of depression and fatigue severity with CRP. The study included 97 depressed individuals, who completed self-administered questionnaires (Multidimensional Assessment of Interoceptive Awareness (MAIA-2); Beck Depression Inventory-II, Multidimensional Fatigue Inventory). CRP concentrations were analyzed in the serum using a particle-enhanced turbidimetric immunoassay. We applied Bayesian inference to estimate robust effect parameters from posterior distributions based on MCMC sampling, and computed Bayes factors (BF 10 ) as indices of relative evidence. The bivariate analysis supported evidence against associations between CRP and self-reported interoception (BF 10 ≤ 0.32), except for one dimension (Not-Distracting: r = 0.11, BF 10 > 0.43, absence of evidence). Positive correlations with overall depression (r = 0.21, BF 10 = 3.19), physical fatigue (r = 0.28, BF 10 = 20.64), and reduced activity (r = 0.22, BF 10 = 4.67) were found. The multivariate analysis showed moderate evidence that low-grade inflammation predicted higher scores on the MAIA-2 Not-Worrying scale (β = 0.28, BF 10 = 3.97), after controlling for relevant confounders. Inflammatory responses, as measured by CRP, may not be involved in the pathophysiology of dysfunctional self-reported interoception. However, systemic low-grade inflammation could potentially exert a protective effect against worries about pain or discomfort sensations. An immunological involvement in interoceptive impairments cannot be ruled out until future studies considering additional biomarkers of inflammation replicate our findings.

Interoception is the sense of the physiological condition of the entire body. Impaired interoception has been associated with aberrant activity of the insula in major depressive disorder (MDD) during heartbeat perception tasks. Despite clinical relevance, studies investigating interoceptive impairments in MDD have never been reviewed systematically according to the guidelines of the PRISMA protocol, and therefore we collated studies that assessed accuracy in detecting heartbeat sensations (interoceptive accuracy, IAc) in MDD (databases: PubMed/Medline, PsycINFO, and PsycARTICLES). Out of 389 records, six studies met the inclusion criteria. The main findings suggest that (i) moderately depressed samples exhibit the largest interoceptive deficits as compared with healthy adults. (ii) difficulties in decision making and low affect intensity are correlated with low IAc, and (iii) IAc seems to normalize in severely depressed subjects. These associations may be confounded by sex, anxiety or panic disorder, and intake of selective serotonin reuptake inhibitors. Our findings have implications for the development of interoceptive treatments that might relieve MDD-related symptoms or prevent relapse in recurrent depression by targeting the interoceptive nervous system.