Cytokine Levels in Panic Disorder: Evidence for a Dose-Response Relationship

Belem da Silva, Cristiano Tschiedel MD, PhD; Costa, Marianna de Abreu MD; Bortoluzzi, Andressa MSc; Pfaffenseller, Bianca MSc; Vedana, Flávia; Kapczinski, Flávio MD, PhD; Manfro, Gisele Gus MD, PhD

doi: 10.1097/PSY.0000000000000384
Original Articles

Objective: Several studies have investigated possible biological correlates of mental disorders. Although some studies have consistently reported elevated levels of serum inflammatory markers in depression, very few have evaluated cytokine levels in patients with lifetime panic disorder (PD).

Methods: Seventy-eight adults (75% women) from an anxiety disorders outpatient unit were categorized according to their PD status: current or in remission. Serum levels of interleukin (IL)-6, tumor necrosis factor α, and IL-10 were evaluated using flow cytometry with enhanced sensitivity flex sets. Data on clinical comorbidity, lipid profile, fasting blood glucose, C-reactive protein, and PD severity were also obtained.

Results: Significantly higher mean levels of serum IL-6 (0.83 vs 0.60 pg/mL [95% confidence interval {CI}for the log-transformed mean difference, −0.41 to −0.57], p = .008) but not of tumor necrosis factor-α (0.18 vs 0.14 pg/mL [95% CI, −1.12 to 0.11]; p = 0.53) or IL-10 (0.21 vs 0.26 [95% CI, −0.20 to 0.44]; p = 0.16), were associated with current PD compared to remitted PD. Higher Panic Disorder Severity Scale (standardized β = 0.36; p = .013), body mass index (standardized β = 0.53, p < .001) and fasting blood glucose 5.6 mmol/L or greater (standardized β = 0.23, p = .038) were significantly associated with higher levels of IL-6 in the multivariate linear regression model.

Conclusions: Our findings support a proinflammatory state in patients with current PD that is independent of possible confounders. Although there are important implications of these findings, replication is required.

From the Federal University of Rio Grande do Sul (Belem da Silva, Costa, Bortoluzzi, Vedana, Kapczinski, Manfro), Brazil; Hospital de Clínicas de Porto Alegre (Belem da Silva, Costa, Bortoluzzi, Pfaffenseller, Vedana, Kapczinski, Manfro), Brazil; Basic Research and Advanced Investigations in Neurosciences (Bortoluzzi, Manfro), BRAIN Laboratory, HCPA; and Laboratório de Psiquiatria Molecular (Pfaffenseller, Kapczinski), Instituto Nacional de Ciência e Tecnologia–Translacional em Medicina (INCT), HCPA, UFRGS.

Supplemental Content

Address correspondence and reprint requests to Cristiano Tschiedel Belem da Silva, MD, PhD, Department of Psychiatry, Hospital de Clínicas de Porto Alegre, 1350 Ramiro Barcelos St, Room 400 N, Rio Branco, Porto Alegre, RS, Brazil. E-mail:

Received for publication October 9, 2015; revision received June 24, 2016.

Copyright © 2017 by American Psychosomatic Society