Inflammatory Response to Stress May Predict CBT Response in Youth With Mood Disorders

Cytokine markers IL-6 and IL-12 appeared to be sensitive to acute psychosocial stress in a laboratory setting.

Study data published in the Journal of Psychiatry Research found modest correlations between immune response to stress and cognitive behavioral therapy (CBT) outcomes in adolescents with mood disorders.

Jennifer G Pearlstein, of the University of California Berkeley, led a preliminary pilot study to assess the feasibility of using inflammation markers to predict CBT response.

Adolescents with a primary mood disorder diagnosis were recruited from the Division of Child and Adolescent Psychiatry at the Stanford University School of Medicine. Eligible diagnoses included major depressive disorder and bipolar disorder types I, II, or not otherwise specified.

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Enrollees participated in a 10-session, 90-minute per week CBT group. Pre and post-group assessments were administered at weeks 1 and 10, respectively, and included stress induction using the Trier Social Stress Test (TSST). Blood samples were taken before the TSST and at 30, 60, and 90 minutes post-TSST and then analyzed for cytokine levels. Hierarchic linear models were conducted for the baseline and follow-up laboratory sessions to assess changes in inflammatory cytokines over time. The area under the curve with respect to increase (AUCi) was calculated for each cytokine; linear regression models using AUCi were performed to predict depressive symptoms at follow-up.

Among 34 adolescents who completed pre- and post- group assessments, 28 had valid cytokine data (mean age, 15.03±1.91 years; 41.2% boys). A significant reduction in depression symptoms as measured by the Children’s Depression Rating Scale was observed at follow-up (P <.05).

Results for the efficacy of cytokine markers were mixed. At baseline, a significant effect of time was observed only for interleukin (IL)-6 (P <.01). At the post-group assessment, a significant effect of time was observed for both IL-12 (P <.05) and IL-6 (P <.001). As such, IL-6 and IL-12 appeared to be sensitive to acute psychosocial stress in a laboratory setting.

At the pre-group assessment, the AUCi for tumor necrosis factor-α and IL-1β (both P <.05) was negatively associated with depressive symptoms. The AUCi for IL-1β was also inversely associated with life stress (P <.05). At follow-up, the AUCi for IL-6 and interferon (IFN)γ were positively associated with depressive symptoms and the AUCi for IL-8 was negatively associated with life stress (all P <.05). In models that predicted follow-up AUCi using baseline AUCi and chronic stress levels, there was a significant main effect of stress for IL-1β (P <.05) and a nominal effect of stress for IL-8 (P =.06) and IFNγ (P =.07). Linear regression markers using AUCi for each inflammatory marker showed mixed results. Models using IL-12 and IL-1β significantly predicted post-group depression symptoms (P <.05).

As study limitations, investigators cited the small study cohort and potential confounding effects of psychotropic medication use in patients. Additionally, cytokines were assessed separately, although inflammatory markers typically operate in tandem.

“Inflammatory response to stress induction is a feasible putative mechanism of change in CBT in youth,” authors wrote.


Pearlstein JG, Staudenmaier PJ, West AE, Geraghty S, Cosgrove VE. Immune response to stress induction as a predictor of cognitive-behavioral therapy outcomes in adolescent mood disorders: a pilot study. J Psychiatr Res. 2019;120:56-63.