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Inflammatory Proteins and Clinical Response to Psychological Therapy in Patients with Depression: An Exploratory Study.

ABSTRACT: In people with depression, immune dysfunctions have been linked with treatment non-response, but examinations of psychological therapy outcomes, particularly longitudinal biomarker studies, are rare. This study investigated relationships between inflammation, depressive subtypes and clinical outcomes to psychological therapy. Adults with depression (n = 96) were assessed before and after a course of naturalistically-delivered psychological therapy. In total, 32 serum inflammatory proteins were examined alongside therapy outcomes and depressive subtypes (somatic/cognitive symptom subtype, and bipolar/unipolar depression). Overall, 49% of participants responded to treatment. High levels of tumour necrosis factor (TNF?), interleukin-6 (IL-6) and soluble intracellular adhesion molecule-1 (sICAM1), and low interferon-? (IFN?), preceded a poorer response to therapy. After therapy, non-responders had elevated c-reactive protein (CRP), thymus and activation-regulated chemokine (TARC) and macrophage chemoattractant protein-4 (MCP4), and attenuated IFNy. Non-somatic depressive symptoms were universally not associated with proteins, while somatic-depressive symptom severity was positively correlated with several pro-inflammatory markers. In the somatic subgroup only, IL-6 and serum amyloid alpha (SAA) decreased between pre- and post-therapy timepoints. Regardless of treatment response, IL-7, IL-8, IL-15 and IL-17 increased over time. These results suggest that inflammation is associated with somatic symptoms of depression and non-response to psychological therapy. Future work may enhance the prospective prediction of treatment-response by examining larger samples of individuals undertaking standardised treatment programmes.

SUBMITTER: Strawbridge R

PROVIDER: S-EPMC7761611 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Inflammatory Proteins and Clinical Response to Psychological Therapy in Patients with Depression: An Exploratory Study.

Strawbridge Rebecca R Marwood Lindsey L King Sinead S Young Allan H AH Pariante Carmine M CM Colasanti Alessandro A Cleare Anthony J AJ

Journal of clinical medicine 20201202 12

In people with depression, immune dysfunctions have been linked with treatment non-response, but examinations of psychological therapy outcomes, particularly longitudinal biomarker studies, are rare. This study investigated relationships between inflammation, depressive subtypes and clinical outcomes to psychological therapy. Adults with depression (<i>n</i> = 96) were assessed before and after a course of naturalistically-delivered psychological therapy. In total, 32 serum inflammatory proteins ...[more]

PMID: 33276697

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Project description:BackgroundInflammation can modulate tumour growth and progression, and influence clinical response to treatment. We investigated the potential of circulating inflammatory proteins for response stratification of immune checkpoint inhibitor (ICI) therapy for advanced melanoma.MethodsStudy subjects were 87 patients with unresectable stage III or IV cutaneous melanoma from the multiple centres across the United Kingdom (UK) and the Netherlands (NL) who received ipilimumab, nivolumab, or pembrolizumab, or a combination of ipilimumab and nivolumab. Serum samples were collected before and during ICI therapy at follow-up visits scheduled every third week over a 12-week period. We performed targeted quantification of 92 proteins involved in inflammation and tested for association of their pre-treatment and on-treatment levels, as well as longitudinal changes, with overall response rate, progression-free survival, and overall survival.FindingsWe observed consistently higher pre-treatment levels of interleukin-6 (IL-6), hepatocyte growth factor (HGF), and monocyte chemotactic protein 2 (MCP-2), in non-responders compared to responders (meta-analysis p=3.31 × 10-4, 2.29 × 10-4, and 1.02 × 10-3, respectively). Patients' stratification according to the median value of IL-6, HGF, and MCP-2 highlighted a cumulative negative effect of pre-treatment levels of the three proteins on response (p=1.13 × 10-2), with overall response rate among patients presenting with combined elevated IL-6, HGF, and MCP-2 levels being three-fold lower (26.7%) compared to patients with none of the three proteins elevated (80.0%, p=9.22 × 10-3). Longitudinal data analysis showed that on-treatment changes in circulating inflammatory proteins are not correlated with response.InterpretationOur findings are in line with an increasing body of evidence that the pro-inflammatory cytokine IL-6 can influence response to ICI in advanced melanoma, and further support a role of circulating HGF and MCP-2 levels as prognostic biomarkers as suggested by previous smaller studies. Inflammatory proteins may serve as predictive biomarkers of ICI response and valuable targets for combination therapy.FundingThis work was supported by the Seerave Foundation and Dutch Cancer Society.

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Inflammatory Proteins and Clinical Response to Psychological Therapy in Patients with Depression: An Exploratory Study.

Publications

Inflammatory Proteins and Clinical Response to Psychological Therapy in Patients with Depression: An Exploratory Study.

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