Serum chemokine levels in major depressive disorder
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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