Journal of Alternative Complementary & Integrative Medicine Category: Medicine Type: Brief Report
Mindfulness-Based Cognitive Therapy Associated with Decreases in C-Reactive Protein in Major Depressive Disorder: A Pilot Study
- Stuart J Eisendrath1*, Erin Gillung2, Abby Hartzler2, Molly James-Myers2, Owen Wolkowitz2, Walter Sipe2, Dhakshin Ramanatham2, Kevin Delucchi2
- 1 Department Of Psychiatry, University Of California, 401 Parnassus Avenue, San Francisco, CA 94143-0984, United States
- 2 Department Of Psychiatry, University Of California, San Francisco, California, United States
*Corresponding Author:Stuart J Eisendrath
Department Of Psychiatry, University Of California, 401 Parnassus Avenue, San Francisco, CA 94143-0984, United States
Received Date: Apr 14, 2016 Accepted Date: Jun 02, 2016 Published Date: Jun 16, 2016
There appears to be growing evidence that there is a relationship between major depressive disorder and inflammation. This study investigates the relationship between depression and C-Reactive Protein (CRP), a marker for inflammation. We utilize mono-treatment with Mindfulness-Based Cognitive Therapy (MBCT) as the independent variable in this investigation. To our knowledge, this is the first study to explore whether MBCT mono-treatment may affect an inflammatory biomarker in major depressive disorder. In an open trial, 11 participants had blood samples taken pre- and post-intervention. Results indicate that there significant decreases in CRP levels as well as depression severity ratings. These results suggest that further investigation with a randomized controlled trial could yield more substantial information about the relationship of inflammation and the psychotherapeutic treatment of major depression. This information may have implications for future targets of depression treatment.
Trial registration: CurrentTrials.gov Identifier; NCT02385786 Registered 10 March 2015.
C-Reactive Protein (CRP)
Hamilton depression rating score-17 (HAMD-17)
Major Depressive Disorder (MDD)
Mindfulness-Based Cognitive Therapy (MBCT)
Quick Inventory of Depressive Symptoms-Self Report-16 (QIDS-SR16)
Randomized Controlled Trial (RCT)
The relationship between depression and inflammation is still evolving. Harley et al.,  noted that elevated CRP is a predictor of good long-term outcomes with antidepressant treatment and poor outcome with psychotherapy, although there was only a small sample of individuals with high CRP. Dahl et al.,  investigated cytokines and CRP in depressed individuals receiving nonpharmacological treatment with weekly support and psychotherapy as compared with those receiving antidepressants. Both samples had reductions in cytokines with recovery, the nonpharmacological sample significantly so. Neither sample had changes in CRP. Krogh et al.,  investigated the effects of exercise on IL-6 and CRP in a depressed population. They noted that there were no significant changes in either parameter after 3 months. Clearly there is further explorations are needed.
Participants were 8 female and 3 male outpatients, aged 20 to 48 years old, who met DSM-IV diagnoses of MDD through evaluation with the Structured Clinical Interview for DSM-IV diagnosis. This instrument and other ratings were completed by a clinical assessor not involved in the intervention. Participants were not taking medications for depression for at least 3 months, were not in psychotherapy, and had minimum Hamilton Depression Rating Score-17 items (HAMD17) scores of 17, indicating moderate to severe depressive symptoms upon entry into MBCT. Measures of depression severity and blood samples were collected pre - (T1) and post-MBCT intervention (T2). We used the HAMD17 as the primary outcome measure and also evaluated the change in inflammation using the CRP following MBCT. We utilized the Quick Inventory of Depressive Symptoms-Self Report-16 (QIDS-SR16) as a secondary outcome. We ruled out medical illness using a clinical review of systems. Participants were enrolled consecutively.
Depressed subjects participated in an 8-week MBCT structured group therapy intervention emphasizing mindfulness meditation training that included components of Cognitive-Behavioral Therapy. Classes were taught in 8 weekly consecutive sessions that were 2 hours and 15 minutes in duration and were led by a psychiatrist and a master’s level therapist. Both the curriculum and format were developed by Segal et al.,  with modifications by Eisendrath et al.,  for an actively depressed population. Patients were asked not to start other treatments during the intervention.
Blood samples were collected within one week before T1 and after T2 and subjects were assessed by clinical history to rule out any concurrent or recent infections. To standardize potential diurnal CRP variation, whole blood samples were collected via venipuncture between 10 am and noon. The blood was then centrifuged @ 400rpm and the serum collected and stored at -800C pending analysis. All samples were shipped on dry ice for analysis at the same time to Myriad RBM for Human Inflammation ELISA bioassay for high-sensitivity CRP. The normal Myriad RBM range for CRP is 0.28 to 10ug/mL.
RESULTS AND DISCUSSION
|Characteristics (n=11)||Mean/Description||Standard Deviation|
|Patient age||34.9 (20-48) years||7.91|
|Ethnicity||9 White/2 Hispanic|
|Employment Status||4 Full/4 Part/3unemployed|
|Age of first major depressive episode||24.8||6.64|
|Number of MDE||3.4||1.51|
|Suicide Score (Item 3 HAMD)||1||0.77|
|Length of MDE||48.5 months||53.7|
|Per Cent free of psychotropic medications>3 months||100%|
|No active substance abuse||11|
The mean change in CRP, HAMD17, and QIDS-SR16 between T1 and T2 were analyzed using student’s one-sample t-tests for significance. Mean CRP decreased from 1.82 mg/L at T1 to 1.32 at T2 (t (20) = 2.21, p=0.0517). This represented an effect size of 0.66 (Cohen’s d, moderately large). The HAMD-17 score decreased significantly from 18.55 to 9.36 (t (20) = 5.76, p<0.0001) with an effect size of 2.08 (Cohen’s d, large). The QIDS-SR16 showed a similar decrease from 21.90 to 11.88 (t (18) = 3.824, p=0.001) with an effect size of 0.85 (Cohen’s d, large). These outcomes are portrayed in table 2.
|Measure Means||Pre-MBCT (T1)||Post-MBCT (T2)||Significance|
|CRP||1.82 ug/mL||1.32 ug/mL||p=0.0517|
To date, this is the first evidence that MBCT targeting depression has the potential to modulate inflammation in depressed patients without medical illness. CRP change from T1 to T2 was nearly significant (p=0.0517), and we expect that given a larger sample size, CRP change would have a better chance of meeting full significance. This finding raises many questions. If MBCT leads to decreased inflammation, how does it have this effect? Might change in inflammatory processes be the mediators of MBCT’s effects on depression, or might MBCT reduce depression with consequent decreased inflammatory processes? Our small sample size limited our assessment of correlation between CRP and HAMD-17 scores and may be why this finding was statistically not significant. Given the growing evidence that a subset of depressed individuals are likely to demonstrate increased inflammation [15,16], does inflammation level make an individual more or less sensitive to MBCT? Future research via a full, Randomized Controlled Trial (RCT) could address these questions as well as contribute to furthering the understanding of the pathophysiology of MDD.
CRP is an acute phase protein that responds to cytokines and gives evidence of inflammation. Cytokines have been shown to access the brain and cause negative effects on neurogenesis, neurotransmitter metabolism, and neuroendocrine function, all processes known to be involved in depression . Research has shown that mindfulness meditation can also affect the brain through each of these domains [17-22]. How mindfulness meditation brings about its effects in these domains, and whether this involves inflammatory cytokines remains unclear. Kaliman et al.,  found decreased pro-inflammatory gene (RIPK2 and COX2) expression in meditators compared with controls. Malarkey et al.,  found that a mindfulness-based intervention for an employee program was associated with a decrease in CRP compared to controls that approached significance (p=0.08). If change in inflammation mediates MBCT effects on depression, it may be that MBCT affects inflammatory cytokines via similar mechanisms as delineated by Kaliman et al.,  and Malarkey et al., .
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Citation: Eisendrath SJ, Gillung E, Hartzler A, James-Myers M, Wolkowitz O et al. (2016) Mindfulness-Based Cognitive Therapy Associated with Decreases in C-Reactive Protein in Major Depressive Disorder: A Pilot Study. J Altern Complement Integr Med 2: 010.
Copyright: © 2016 Stuart J Eisendrath, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.