title: Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction.
abstract: BACKGROUND
  Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.
  
  
  METHODS
  160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.
  
  
  RESULTS
  Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p=0.000001, macrophage colony-stimulating factor 1 (CSF-1), p=0.000004, and fractalkine (CX3CL1), p=0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p=0.000011, vascular endothelial growth factor A (VEGF-A), p=0.000016, and IL-15 receptor subunit alpha (IL-15RA), p=0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.
  
  
  CONCLUSIONS
  Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Edvinsson
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Bränn
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hellgren
authors.affiliation: Department of Medical Science, Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Freyhult
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Richard
authors.initials: R
authors.lastname: White
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Masood
authors.initials: M
authors.lastname: Kamali-Moghaddam
authors.affiliation: Department of Neurobiology, Unit Behavioral Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, The Netherlands.
authors.forename: Jocelien
authors.initials: J
authors.lastname: Olivier
authors.affiliation: Department of Chemistry, Analytical Chemistry and SciLifeLab, Uppsala University, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Boström
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Alkistis
authors.initials: A
authors.lastname: Skalkidou
authors.affiliation: Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Cunningham
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. Electronic address: inger.sundstrom@kbh.uu.se.
authors.forename: Inger
authors.initials: I
authors.lastname: Sundström-Poromaa
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003863:Depression / Q000150:complications / Q000276:immunology*; D003866:Depressive Disorder / Q000188:drug therapy; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology* / Q000378:metabolism / Q000523:psychology*; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D017367:Selective Serotonin Reuptake Inhibitors / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antenatal depression; Inflammatory markers; Pregnancy; Proximity extension assay; Selective serotonin reuptake inhibitors