Depression treatment response to ketamine: sex-specific role of interleukin-8, but not other inflammatory markers
Jennifer L. Kruse, Megha M. Vasavada, Richard Olmstead, Gerhard Hellemann, Benjamin Wade, Elizabeth C. Breen, John O. Brooks, Eliza Congdon, Randall Espinoza, Katherine L. Narr, Michael R. Irwin
Translational Psychiatry March 21, 2021 Peer reviewed DOI: 10.1038/s41398-021-01268-z via DOAJ
Summary
Lower levels of interleukin-8 (IL-8) may predict how well depressed patients respond to ketamine treatment, with significant differences observed between sexes. In a study of 46 depressed patients, lower baseline IL-8 levels in females were associated with better treatment response, while no such association was found in males. Changes in IL-8 levels also correlated with changes in depression scores, but this relationship varied by sex, indicating that IL-8's role in treatment response may differ between men and women.
Study at a glance
| Design | open label trial |
|---|---|
| Sample size | 46 |
| Population | depressed patients receiving ketamine treatment |
| Key finding | Lower baseline levels of IL-8 in females trended with better response to ketamine treatment, while no similar trend was observed in males. |
Abstract
Abstract Inflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.