Stress-induced pro- and anti-inflammatory cytokine concentrations in panic disorder patients

An attenuated responsivity of the hypothalamus-hypophysis-adrenal (HPA) axis upon challenge and an increased risk for cardiac events are relatively consistent findings in panic disorder (PD) patients. Due to cytokine-HPA interactions, an altered HPA-axis responsivity may be accompanied by altered cytokine concentrations. Immunological reactions under stress might be considered the missing link for explaining an increased cardiac risk. This study analyzed stress-induced cytokine levels in PD patients.

A total of n = 32 PD patients and n = 32 healthy control individuals performed the Trier Social Test (TSST). Blood sample collection accompanied the TSST for the collection of cortisol and pro- (IL-6, TNF-α) and anti-inflammatory cytokines (IL-10). Established self-report questionnaires were handed out for the clinical characterization and the assessment of subjective levels of distress during testing. Repeated measures ANCOVA were conducted to evaluate main effects of time or group and time x group interaction effects. Additional ANCOVAS with disease severity as between-subjects factor (healthy, borderline, mild, moderate, severe) took global panic severity into account. Pearson correlation analyses were carried out to test for an association of panic specific symptoms and peak cytokine release.

The TSST resulted in a significantly increased secretion of cortisol, IL-6 and IL-10. The data analysis further revealed a significant time x group interaction effect for cortisol and IL-10. Compared to the healthy volunteers, the PD patients showed significantly higher baseline and challenged IL-10 concentrations but lower challenged cortisol concentrations. Mildly and moderately affected patients showed the highest levels of IL-10 compared to the healthy individuals. There were no differential secretion patterns of IL-6 and TNF-α between both groups in the course of the TSST. The peak IL-6 release was found to be significantly associated with global disease severity.

We found evidence for altered levels of cytokines with primarily anti-inflammatory properties in PD patients under baseline and a psychosocial stress condition. The results provide tentative evidence for a low-grade inflammatory process in PD patients, possibly representing a missing link factor between PD diagnosis and the increased risk for cardiac disease.