Metabolic Profiling Indicates Diversity in the Metabolic Physiologies Associated With Maternal Postpartum Depressive Symptoms.

Background: Postpartum depression (PPD) is a devastating disease requiring improvements in diagnosis and prevention. Blood metabolomics identifies biological markers discriminatory between women with and those without antenatal depressive symptoms. Whether this cutting-edge method can be applied to postpartum depressive symptoms merits further investigation. Methods: As a substudy within the Biology, Affect, Stress, Imagine and Cognition Study, 24 women with PPD symptom (PPDS) assessment at 6 weeks postpartum were included. Controls were selected as having a score of ≤ 6 and PPDS cases as ≥12 on the Edinburgh Postnatal Depression Scale. Blood plasma was collected at 10 weeks postpartum and analyzed with gas chromatography-mass spectrometry metabolomics. Results: Variations of metabolomic profiles within the PPDS samples were identified. One cluster showed altered kidney function, whereas the other, a metabolic syndrome profile, both previously associated with depression. Five metabolites (glycerol, threonine, 2-hydroxybutanoic acid, erythritol, and phenylalanine) showed higher abundance among women with PPDSs, indicating perturbations in the serine/threonine and glycerol lipid metabolism, suggesting oxidative stress conditions. Conclusions: Alterations in certain metabolites were associated with depressive pathophysiology postpartum, whereas diversity in PPDS physiologies was revealed. Hence, plasma metabolic profiling could be considered in diagnosis and pathophysiological investigation of PPD toward providing clues for treatment. Future studies require standardization of various subgroups with respect to symptom onset, lifestyle, and comorbidities.

Cohort profile: the Biology, Affect, Stress, Imaging and Cognition (BASIC) study on perinatal depression in a population-based Swedish cohort.

PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection. PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort. FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system. FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.

Spring peaks and autumn troughs identified in peripheral inflammatory markers during the peripartum period.

Seasonal variations have recently been described in biomarkers, cell types, and gene expression associated with the immune system, but so far no studies have been conducted among women in the peripartum period. It is of note that pregnancy complications and outcomes, as well as autoimmune diseases, have also been reported to exhibit seasonal fluctuations. We report here a clear-cut seasonal pattern of 23 inflammatory markers, analysed using proximity-extension assay technology, in pregnant women. The inflammatory markers generally peaked in the spring and had a trough in the autumn. During the postpartum period we found seasonality in one inflammatory marker, namely monocyte chemotactic protein 4 (MCP-4). Our findings suggest that seasonal variations in peripheral inflammatory markers are only observed during pregnancy. The results of this study could be valuable to professionals working within the field of immunology-related areas, and provide insight for the understanding of obstetric complications.

Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms.

Antenatal depression affects ~9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.

Meteorological parameters and air pollen count in association with self-reported peripartum depressive symptoms.

BACKGROUND: Meteorological parameters and air pollen count have been associated with affective disorders and suicide. Regarding peripartum depression, the literature is restricted and inconclusive. METHODS: This cross-sectional study included women (pregnant, n = 3843; postpartum, n = 3757) who participated in the BASIC (Biology, Affect, Stress, Imaging, and Cognition) study 2010-2015 and the UPPSAT (Uppsala-Athens) study (postpartum, n = 1565) in 2006-2007. Cases were defined according to presence of depressive symptoms during pregnancy (gestational week 32) and 6 weeks postpartum, using the Edinburgh Postnatal Depression Scale (EPDS). Exposure of sunshine, temperature, precipitation, snow coverage, and air pollen counts of durations of 1, 7, and 42 days prior to the outcome were studied for associations with depressive symptoms, using negative binomial regression. RESULTS: Prior to Bonferroni correction, the concentration of mugwort pollen, both one week and six weeks before the EPDS assessment at gestational week 32, was inversely associated with depressive symptoms in pregnancy, both before and after adjustment for season. No associations were found between the exposure to meteorological parameters and pollen and depressive symptoms, at the same day of depressive symptoms' assessment, the previous week, or the six weeks prior to assessment, either during pregnancy or postpartum after Bonferroni correction. CONCLUSIONS: There was no evidence that neither short-term nor long-term exposure to meteorological parameters or air pollen counts were associated with self-reported peripartum depressive symptoms in Uppsala, Sweden.