Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: differential reactivity in bipolar disorder.

Mounting evidence suggests a chronic pro-inflammatory state in individuals with bipolar disorder (BD). Stress exposure is known to exacerbate several inflammatory conditions as well as psychiatric disorders. Here, we analyzed plasma levels of pro-inflammatory cytokines and their soluble receptors to realistic acute psychosocial stress challenge in BD. Thirteen euthymic type 1 BD patients and 15 matched controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST and plasma cytokines interleukin IL-2, IL-6, IL-33, and tumor necrosis factor alpha (TNF-α) were measured. In addition TNF-α soluble receptors TNFR1 and TNFR2, and IL-33 soluble receptor sST2 were assessed. Increased IL-33 and reduced sST2 levels were observed in BD subjects as compared to controls, independently of stress exposure. Following TSST, there were higher levels of IL-2 and reduced levels of sTNFR1 in both groups. However, the magnitude change for both cytokines was found higher in controls than BD subjects. Our data suggest that BD patients have differential stress reactivity as compared to controls, possibly related to an immunologic imbalance and failure of regulatory mechanisms.

Differential neuroendocrine and immune responses to acute psychosocial stress in women with type 1 bipolar disorder.

Bipolar disorder (BD) has been associated with immune imbalance, including lymphocyte activation and increased pro-inflammatory cytokines. Immune activation is part of stress response, and psychosocial stress has been implicated in the pathogenesis of psychiatric disorders. Here, we investigated the neuroendocrine and immune responses to acute psychosocial stress challenge in BD. Thirteen euthymic participants with type 1 BD and 15 healthy controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST. Lymphocytes were isolated and stimulated in vitro to assess lymphocyte activation profile, lymphocyte sensitivity to dexamethasone, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling by flow cytometry. Heart rate and salivary cortisol levels were monitored across the task. BD participants exhibited blunted stress responses as shown by reduced heart rate and salivary cortisol levels in comparison to healthy controls. BD was also associated with reduction in the percentage of regulatory T cells, but with expansion of activated T cells. When compared to controls, patients showed increased lymphocyte MAPK p-ERK and p-NF-κB signaling after the stress challenge, but exhibited a relative lymphocyte resistance to dexamethasone. In conclusion, stress-related neuroendocrine responses are blunted, associated with increased immune activation and lower sensitivity to glucocorticoids in BD. An inability in reducing NF-κB and MAPK signaling following TSST could be underlying the immune imbalance observed in BD.