Social Stress Heightens Risk for Depression Through Inflammatory Response

Heightened inflammatory reactivity to social stress appears to increase the risk for depression in adolescent girls, according to the results of a study published in Depression and Anxiety.¹ These findings provide further support for the Social Signal Transduction Theory of Depression, as proposed by Michael Irwin, MD, and George Slavich, PhD, of the Cousins Center for Psychoneuroimmunology, University of California, Los Angeles.²

Depression frequently emerges in adolescence and over the lifetime is associated with an increased risk for serious immunologic-related disorders such as asthma, chronic pain, cardiovascular disease, and autoimmune and neurodegenerative disorders. Following the onset of puberty, the rate of depression increases 5-fold and compared with boys, girls have twice the risk of developing major depressive disorder. In adolescent girls, interpersonal life stress is a strong predictor of depression.

Dr Slavich and colleagues enrolled 116 adolescent girls (mean age, 14.71 years, range 12-16 years; 65.5% white) at risk for psychopathology. They characterized baseline inflammatory reactivity to social stress by quantifying salivary proinflammatory cytokine responses to social stressors using the laboratory-based Trier Social Stress Test. The task involved preparing and delivering a speech in front of a camera with a judge in the room. Proinflammatory cytokines selected for study were tumor necrosis factor-alpha (TNF‐α), interleukin (IL)‐1β, and IL‐6. After 9 months, the researchers assessed stressful life events the participants had experienced in the interim, as well as depressive symptoms.

There were significant increases in depression over time in association with greater interpersonal life stressors in girls who had elevated salivary TNF‐α and IL‐1β reactivity to social stress at baseline (both P <.001). No significant relationship was found for non-interpersonal stress exposure or IL-6.

The study authors hypothesized that, “TNF‐α and especially IL‐1β are the predominant mediators of sickness behavior in the brain, and, therefore, could potentially be better markers of stress-related vulnerability for depression than IL-6.”  They admitted, however, that this may also be related to the earlier release of TNF‐α and IL‐1β than IL-6 in the inflammatory cascade.

The researchers noted several limitations, including the fact that salivary cytokines are not interchangeable with serum levels and that they may be sensitive to acquisition methods, salivary flow rate, oral hygiene, and sleep quality. Furthermore, the use of only female adolescents in the study population may limit generalizability to other populations, particularly boys.

Slavich et al concluded, “To the extent that interventions can be developed to modify negative stress-related cognitions that drive inflammatory reactivity, such interventions may be helpful for reducing inflammation‐related depression and physical disease risk.”

Reference

1.  Slavich GM, Giletta M, Helms SW, et al. Interpersonal life stress, inflammation, and depression in adolescence: Testing Social Signal Transduction Theory of Depression. Depress Anxiety. 2020;37:179-193.

2.  Slavich, GM & Irwin MR. From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin. 2014;140:774-815. doi:org/10. 1037/a0035302