Abstract
Objective: In experimental settings, systemically elevated inflammation markers interfere with major depression treatment. In German healthcare, compulsory national health insurance covers treatment of a wide variety of depressive disorders, if it follows evidence-based medicine guidelines combining recommended therapies. To date, little is known about the relevance of immune system cytokine production with regard to real-world clinical care for patients with moderate depression.Methods: Seventy three patients with moderate depression subjected to multimodal psychotherapeutic inpatient therapy (mPT) following a psychodynamic concept at a German university hospital were included. As a primary outcome, mPT success, evidenced by delta HADS “depression,” was analyzed according to tumor necrosis factor alpha (TNFα) production by peripheral blood mononuclear cells (PBMC) after phytohemagglutinin (PHA) challenge at baseline. Secondary outcomes addressed the inflammatory response and mental health comparing high and low TNFα-producers.Results: First, higher PBMC TNFα production at baseline predicted a better mPT-outcome (R2 0.162, p = 0.014). Second, patients with high TNFα (hTNF) at baseline produced significantly more acute inflammatory cytokines [interleukin (IL)1β, IL6), TH1/TH2 cytokines [interferon gamma (IFNγ), IL4] as well as eotaxin and IL2 compared to low TNFα producers (lTNF) (Cohen's ds between −0.532 and −1.013). Demographic data, diagnosis subtype-distribution, medication, systemic inflammation markers [C-reactive protein (CRP), high mobility group box 1 (HMGB1), leptin], anxiety and depression (HADS) did not differ. From baseline to mPT-discharge, HADS “depression” decreased in both hTNF (11.31 to 5.47, p = 0.001, d = 1.184) and lTNF patients (11.50–7.92, p = 0.001, d = −0.765), while PBMC cytokine production decreased significantly in hTNF (Cohen's ds between −0.304 and −0.345) with a significant group by time interaction for TH1/TH2 ratio. At the end of therapy, comparison of TNF groups revealed significantly lower depression-scores in hTNF compared to lTNF patients (5.47 compared to 7.92, p = 0.035, d = 0.504).Conclusions: Our study demonstrates successful treatment of depression in a clinical care setting using multimodal psychotherapy based on a psychodynamic concept following guideline recommendation. The greatest improvement in patient depression was linked to the highest production of TNFα by PBMCs at baseline. Our study contributes to the definition of patient subpopulations with differing cytokine responses that are related to succesful treatment of depression.
Highlights
The interaction between depression and inflammation is an intensely debated topic [1,2,3,4,5,6,7,8]
We found that baseline TNFα production of peripheral blood mononuclear cells (PBMC) in response to PHA challenge predicted multimodal psychotherapeutic inpatient therapy (mPT) outcomes, and higher logTNFα at T1 predicted higher improvement of Hospital Anxiety and Depression Scale (HADS) “depression” (delta HADS “depression” = T2 scores—T1 scores) in the total patient sample
We report a significant response to multimodal psychotherapeutic inpatient therapy following a psychodynamic concept in patients with moderate depression and high production of TNFα by PBMC at the time of hospital admission
Summary
The interaction between depression and inflammation is an intensely debated topic [1,2,3,4,5,6,7,8]. Evidence is accumulating that stress-exaggerated inflammation can contribute to the development of depression and at the same time promote infections and non-communicable diseases such as autoimmune, metabolic or cardio-vascular disease [9,10,11,12,13,14] Such maladaptive inflammatory activity is held partly responsible for the frequent co-morbidities that accompany depressive disorders and with the increased medical care required for respective patients. Present concepts of the role of inflammation in depression are based on randomized controlled trials employing mostly patients suffering from major depressive disorder [15] In these studies, depression is associated at it’s peak with high levels of general inflammation markers such as C-reactive protein (CRP) as well as high levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6). Due to the observation that patients with major depression and high levels of inflammation markers appear to be more resistant to pharmacologic or behavioral treatment [11, 20, 22,23,24,25,26], this topic warrants further investigation of the role of inflammation in different therapeutic approaches and patient subpopulations
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