Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

Association between inflammatory biomarkers before pregnancy and risk of perinatal depression: A prospective cohort study of 4483 women in Sweden.

AIM: Perinatal depression (PND) is a global health concern, affecting millions of childbearing women. Emerging data suggest that inflammation may play a role in the development of PND. Peripheral blood inflammatory biomarkers before pregnancy are widely tested in clinical practice at minimum cost, yet their potential role in PND risk remains unknown. METHODS: We conducted a prospective cohort study of 4483 birthing women during 2009-2021 within the LifeGene study with linkage to Swedish registers. Peripheral blood inflammatory biomarkers were profiled at baseline. Cases of PND were identified using validated tools or clinical diagnosis from subsequent pregnancies and postpartum periods. Logistic regression models were employed to assess the associations of each inflammatory biomarker (z scored) with PND. RESULTS: We identified 495 (11.0 %) PND cases with an average age of 29.2 years. Pre-pregnancy platelet-to-lymphocyte ratio (PLR) was positively associated [OR, 95 % CI:1.14(1.01,1.27)], while lymphocyte count was inversely associated [OR, 95 % CI: 0.89(0.80,0.98)] with PND. A dose-response relationship was indicated for both PLR and lymphocytes when analyzed in categories based on tertile distribution. These associations appeared more pronounced for postpartum depression than antepartum depression and were independent of psychiatric comorbidities. CONCLUSION: With implications for future mechanistic research, these findings suggest that blood levels of lymphocytes and PLR before pregnancy are associated with subsequent risk of PND in a dose-response manner.