br Materials and methods br Acknowledgements SD
Materials and methods
Acknowledgements SD was supported by a pre-doctoral research fellowship from the Flanders Agency for Innovation and Entrepreneurship (VLAIO-Flanders, Belgium). YB is supported by a postdoctoral fellowship from Research Foundation Flanders (FWO, Belgium). We thank Isabelle Geron (PerkinElmer) for support in the design and optimization of AlphaLISA assays, the VIB Screening Core for technical assistance regarding the EnVision Plate reader used in the AlphaLISA assays, and the BCCM/GeneCorner (http://bccm.belspo.be) for providing the IL-6 gene. SNS acknowledges research support from Research Foundation Flanders (FWO, Belgium) (grants G0E1516N, G0B4918N), the Hercules Foundation (Belgium) (grant AUGE-11-029), and the VIB.
Depression is becoming increasingly recognized as a disorder of immune hyperactivation., , , , , , , Patients with major depressive disorder have increased plasma inflammatory biomarkers, most consistently interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein., Blockade of the production of these cytokines is associated with reduced depressive symptoms., , , Studies in the perinatal period have suggested that postpartum depression is associated with increased plasma inflammatory biomarkers, most consistently IL-1β, soluble IL-1 receptor antagonist, and IL-6., , , While peripheral cytokines are able to cross the blood-brain barrier, equilibrium between cerebrospinal fluid (CSF) and plasma is not established and peripheral blood markers may not reflect the intracerebral environment milieu. Although cytokines are large molecules, a variety of mechanisms facilitate transport between plasma and CSF. These include the following: (1) leaky regions of the blood-brain barrier, (2) Costunolide via various facilitative molecules, (3) activation of cells surrounding the cerebral vasculature, and (4) binding of cytokine receptors on peripheral afferent nerve fibers. When inflammatory cytokines are present in the CSF, they can cause damage to existing nerve cells as well as inhibition of neural cell growth in the hippocampus, amygdala, prefrontal cortex, anterior cingulate, and basal ganglia, which leads to symptoms of depression. There is conflicting reported evidence between depressive symptomatology and CSF inflammatory biomarkers (). Heterogeneity in research methodology, including indications and circumstances for undergoing a lumbar puncture, may explain some of these reported differences. Pregnancy further complicates the inflammatory assessment because normal pregnancy represents a state of immunologic changes. As pregnancy progresses, increases in peripheral phagocytic (monocytes and granulocytes) and dendritic cells have been observed that are partially offset by decreases in CD4, CD8, B, and NK cells. Correspondingly, plasma cytokines and chemokines involved in phagocytic recruitment, such as TNFα, increase, whereas plasma inflammatory molecules, such as vascular endothelial growth factor and interferon (IFN)-γ decrease throughout gestation. Despite these changes, perinatal depression has been shown to be associated with increased plasma inflammatory cytokines, similar to major depressive disorder outside pregnancy., , , The association between depressive symptomatology and CSF inflammatory cytokines has not been well established in pregnant patients. A positive correlation between CSF IL-6 and TNFα and scores on the Edinburgh Postnatal Depression Scale has been reported in parturients; however, the authors did not account for the potential underlying impact of labor itself or establish clinical diagnoses of major depressive disorder. Perinatal depression, or depression that begins either during pregnancy or within 12 months postpartum, is one of the most common complications of pregnancy affecting approximately 1 in 7 women., However, the majority of women with depression are neither identified nor treated., This disparity between clinical need and care provision is not due to a lack of access to the health care system in general because contact with health care professionals is typically increased in the perinatal period. The unmet need reflects barriers to mental health care. Furthermore, current treatments are not often fully effective, and only a minority of women achieve a therapeutic response.,