Elgeta Hysaj

Background: Major psychiatric disorders (MPDs) and premenstrual disorders (PMDs) are often comorbid, with indications of shared genetic architecture. However, the specific genetic variants underlying this comorbidity remain elusive. The aim of this study was to identify genomic loci shared between MPDs and PMDs, and to assess the functional characteristics of genes mapped to these loci. Methods: We used genome-wide association data for symptoms of PMDs (S-PMD, n = 67 068) from the Norwegian Mother, Father and Child Cohort Study (MoBa), and for MPDs (schizophrenia, n = 130 644; bipolar disorder, n = 827 335; major depression, n = 1 918 432) from the Psychiatric Genomic Consortium. Shared genetic loci were identified with the conjunctional false discovery rate (conjFDR). Genes mapped to the identified loci were included in functional and pharmacological gene-set enrichment analyses (GSEAs). Results: We identified 20 loci shared between S-PMD and the MPDs, including 19 novel loci for S-PMD (conjFDR<0.05). GSEA revealed genes involved in calcium signaling and neuronal projection pathways. The drug enrichment analysis identified 36 drugs, including riluzole and mianserin, significantly associated with the identified molecular pathways. Conclusions: We identified 20 genetic loci shared between the S-PMD and MPDs, implicating calcium transmission in the pathogenesis of PMDs. Together with the drug enrichment results, this provides a biological basis for repurposing existing drugs in the treatment of PMD.

Background: Premenstrual disorders (PMDs) are prevalent and impair women’s quality of life, but their long-term influence on work capacity is unclear. Understanding the association between PMDs and subsequent sick leave and unemployment could inform interventions and policies. Objective: We hypothesised that women with PMDs have an increased risk of future sick leave and unemployment compared with those without PMDs. Methods: We conducted a prospective cohort study involving 15 857 women aged 15–60 years who were employed at baseline in the LifeGene Study, with linkage to population and health registers in Sweden. PMDs were identified from clinical diagnoses and symptom questionnaires; sick leave and unemployment data were obtained from national registers. Poisson regression estimated incidence rate ratios (IRRs) for sick leave and unemployment in women with versus without PMDs. Findings: A total of 2585 (16.3%) women (mean age 32.5 years) had probable PMDs. Over a median 9.17-year follow-up, 6741 (42.5%) and 1485 (9.4%) experienced at least one sick leave or unemployment, respectively. Compared with women without PMDs, those with PMDs had a 40% higher risk of sick leave (IRR 1.40, 95% CI 1.31 to 1.49) and a 27% higher risk of unemployment (IRR 1.27, 95% CI 1.10 to 1.46). Risk elevations were pronounced for sick leave≥90 days (IRR 1.69, 95% CI 1.50 to 1.91) and depression-related sick leave (IRR 1.41, 95% CI 1.27 to 1.56). Discussion: Women with PMDs are at increased risk of sick leave and unemployment, suggesting significant long-term socioeconomic burden associated with PMDs. Clinical implications: This study underscores the need for greater awareness of PMDs in clinical practice. Healthcare providers should recognise the potential impairment at work associated with PMDs, especially in women with recurrent symptoms or comorbidities like anxiety or depression.

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.