Role of IL-8, CRP and epidermal growth factor in depression and anxiety patients treated with mindfulness-based therapy or cognitive behavioral therapy in primary health care
Introduction
Patients with depression, anxiety and stress and adjustment disorders are common in primary health care, varying between 12% and 32% and cause a lot of sufferings often in middle-aged to young-aged women patients (Berardi et al., 1999, Bodlund et al., 1999, Nordstrom and Bodlund, 2008, Parikh et al., 1997, Vazquez-Barquero et al., 1997).
Dysregulation of the immune system is linked to the pathophysiology of depression and its co-morbidities. For example, higher levels of cytokines such as IL-6 and IL-8 in plasma, serum and cerebrospinal fluid (CSF) are associated with depression and other psychiatric disorders (Dowlati et al., 2010, Maes et al., 1999, Remlinger-Molenda et al., 2012). IL-6 is a well-known proinflammatory cytokine whereas IL-8 may perform either pro- or anti-inflammatory role depending upon the concentration (Kronfol and Remick, 2000). Multiple studies have measured the effect of antidepressant treatment on circulating cytokines levels in major depression; however, the results are not consistent (Hannestad et al., 2011b, Muller et al., 2006, Tyring et al., 2006). Furthermore, little is known about the effect of psychotherapeutic interventions on the levels of cytokines in patients with mild to moderate depression and anxiety.
Epidermal growth factor (EGF) is a member of epidermal growth factor family and its role in cancer risk and its prognosis is well established (Memon et al., 2004). However its role in mental disorders is not well explored despite the fact that EGF serves as a neurotrophic factor to enhance cell proliferation and neuronal differentiation (Xian and Zhou, 1999). Furthermore, aggressive behavior in mice is shown to provoke a marked increase in plasma levels of EGF (Nexo et al., 1981). Moreover, a study on rhesus monkeys shows that EGF activates the hypothalamic-pituitary-adrenal (HPA) axis through stimulation of corticotropin-releasing hormone release from the hypothalamus and such states may include trauma, surgery, and possibly emotional stress (Luger et al., 1988). Finally, few recent studies have shown its role in stress and mood disorders (Wallensten et al., 2016, Yamamori et al., 2016). However its role in mild to moderate depression and anxiety is not known. Also it is not known whether EGF is just a physiological measure of depression and anxiety or it has a role in response to mindfulness based therapy or CBT.
The present study uses data from a randomized controlled trial (RCT) of patients with depression, anxiety and stress-related disorders from 16 primary health care centers in Sweden. In this 8-week RCT, patients were randomized to control group [mainly cognitive based therapy, (CBT)] or intervention group (mindfulness-based group therapy. It was found that mindfulness-based group therapy was as effective as CBT in alleviating mental health symptoms for primary health care patients with depressive, anxiety, or stress and adjustment disorders (Sundquist et al., 2014). However, underlying molecular mechanism associated with the improvement in symptoms of depression and anxiety after CBT or mindfulness-based therapy is not known. We hypothesized that levels of EGF, IL-8, IL-6 and hsCRP were associated with the measure of anxiety and mild to moderate depression and had a role in response to mindfulness based therapy and CBT. Primary aims of the study were to investigate potential effect of mindfulness and CBT on the levels of biomarkers (EGF, IL-8, IL-6 and hsCRP) and their associations with measure of the symptoms of mild to moderate depression and anxiety.
Section snippets
Study participants
The study participants were recruited in a randomized controlled trial (RCT) of mindfulness.
which included a group of patients with mild to moderate depression and anxiety as described earlier (Sundquist et al., 2014). Briefly, eligible patients were aged between 20 and 64 years, who fulfilled the diagnostic criteria, were fluent in Swedish and had a score of ≥10 on the PHQ-9, ≥7 on the HADS-D or HADS-A or a score on the MADRS between 13 and 34. Eligible patients who consent to take part in the
Characteristics and levels of molecular markers at baseline
Table 1 shows baseline characteristics of participants and levels of EGF, IL-8, IL-6 and hsCRP in mindfulness and CBT groups. The mean age of participants randomized in mindfulness and CBT groups was 42 and 41, respectively. Female participants were in majority in both groups, however no significant difference in male and female participants in two groups was found (p=0.09). Median baseline scores for MADRS (22 vs 19, p=0.01), HADS-D (9 vs 8, p=0.01), HADS-A (13 vs 11, p=0.04) and PHQ-9 (13 vs
Discussion
In this study, we show that levels of EGF in patients with mild to moderate depression and anxiety were decreased after both, mindfulness-based therapy and in CBT and were associated with response to both these therapies. In contrast, levels of IL-8 or CRP were not significantly affected by either of these therapies and were not associated with measures of depression and anxiety either in our sample.
We have previously shown that mindfulness-based therapy and CBT are equally associated with
Disclosure statement
Authors declare no conflict of interest.
Acknowledgments
This project was supported by the Swedish Research Council to Jan Sundquist (2012–2378), by the Swedish Research Council to Kristina Sundquist (K2012-70X-15428-08-3), the Swedish Research Council for Health, Working Life and Welfare (In Swedish: Forte; Reg.nr: 2013-1836) to Kristina Sundquist, as well as ALF funding from Region Skåne awarded to Jan Sundquist and Kristina Sundquist.
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