Elsevier

Psychoneuroendocrinology

Volume 35, Issue 2, February 2010, Pages 226-232
Psychoneuroendocrinology

Serum chemokine levels in major depressive disorder

https://doi.org/10.1016/j.psyneuen.2009.06.007Get rights and content

Summary

Objective

To examine the role of chemokines of two major chemokine families, CC and CXC, in major depressive disorder (MDD) in a population-based sample.

Method

The serum levels of CC chemokines MCP-1 and MIP-1β, and CXC chemokine IL-8 were measured from 122 participants (MDD group, n = 61; controls, n = 61). Depression severity was assessed with the 29-item Hamilton Depression Rating Scale.

Results

The MDD group had lower levels of MCP-1, MIP-1β and IL-8 than the healthy controls. The likelihood of major depressive disorder for participants with chemokine levels below the median (MCP-1: <26.26 pg/mL; MIP-1β: <42.57 pg/mL; IL-8: <2.86 pg/mL) was 3.6 (p = 0.002) for MIP-1β and 2.4 (p = 0.037) for IL-8 in regression models adjusted for age, gender, body mass index, smoking, and alcohol consumption. MCP-1 did not associate with the presence of MDD after adjustments for potential confounders. Further adjustments for somatic illnesses or medications did not affect these findings.

Conclusion

Our findings suggest that depression-related alterations of inflammatory markers may be more complex than previously assumed, and that at least some of the chemokines may be down-regulated.

Introduction

Low-grade inflammation has been demonstrated to associate with major depressive disorder (MDD) (Raison et al., 2006). Increased levels of pro-inflammatory cytokines IL-1, IL-2 and IL-6 as well as upregulation of serum indicators of immune activation are observable in MDD (Schiepers et al., 2005). However, data on the role of chemotactic cytokines, i.e., chemokines, in the pathophysiology of depression are scarce.

Chemokines have been divided into two major families, CC and CXC, depending on the presence or absence of an amino acid between the first two NH2-terminal cysteines (Rollins, 1997). In inflammation, they direct cell movements needed to initiate T-cell-mediated immune responses. CC chemokines primarily attract monocytes, whereas CXC chemokines attract neutrophils and lymphocytes (Rollins, 1997, Baggiolini, 1998). Chemokines also have several other functions; they modify hematopoiesis and angiogenesis, and have an antagonist effect in pathological conditions such as HIV-1 infection (Rollins, 1997). In the central nervous system, chemokines are observable under both physiological and pathological conditions (de Haas et al., 2007). They affect cell interaction, neuromodulation, and synaptic transmission, factors that have been demonstrated to be altered in depression (Li and Ransohoff, 2008).

In order to explore the roles of CC chemokines MCP-1 and MIP-1β, and CXC chemokine IL-8 in MDD, we examined the serum levels of these chemokines in 61 MDD subjects and 61 healthy controls in a population-based sample.

Section snippets

Study setting and subjects

This study formed a clinical arm of the Kuopio Depression (KUDEP) four-phase general population study focusing on the mental health of general population adults aged 25–64 years. It was conducted in the province of Kuopio in Eastern Finland. A random sample of 3004 participants was selected in 1998 via the National Population Register. The same sample was followed up in 1999 and 2001. The baseline sample (in 1998) comprised 2050 participants, the first follow-up sample in 1999 a total of 1722

Results

Characteristics of the study sample are summarized in Table 1. The MDD group participants smoked more, had higher depression scores, and lower levels of MCP-1, MIP-1β, and IL-8 than the healthy controls. In the MDD group, the median of the scores for the HAM-D-21 was 12 (range 1–28). No correlations were observable between depression scores and the levels of MCP-1 (HAM-D-21: rho = 0.05, p = 0.71; ADS: rho = 0.07, p = 0.59; HAM-D-29: rho = 0.09, p = 0.51), MIP-1β (HAM-D-21: rho = 0.07, p = 0.57; ADS: rho = −0.01,

Discussion

To the best of our knowledge, this is the first study demonstrating lowered levels of circulating CC and CXC chemokines in MDD. MIP-1β and IL-8 levels were lowered in the MDD group regardless of the adjustments for potential confounders.

Lowered levels of MIP-1β, a pro-inflammatory chemokine, suggest reduced pro-inflammatory chemokine activity in the MDD group compared with healthy controls. This unexpected observation is discordant with the large number of previous investigations reporting an

Role of funding source

SML was supported by funding from Kuopio University Hospital EVO, the Finnish Graduate School of Psychiatry, and research grants from the Foundation for Psychiatric Research and the Finnish Medical Foundation. HK-H was supported by the Academy of Finland (grant 116996). K-HH was supported by a fellowship from the Academy of Finland. The funding had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit

Conflict of interest

None of the authors have financial conflicts or other conflicts of interest in this area.

Acknowledgements

The authors thank Kaisa Haatainen, Ph.D., and Tarja Saharinen, M.N.Sc. for their valuable contribution to the KUDEP study.

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