PREPRINT: Associations between hair endocannabinoid concentrations and parental depressive symptoms: A longitudinal study of mothers, fathers, and their offspring up to two years postpartum

Background: About one in five mothers and one in ten fathers experience postpartum depression, withadverse consequences for family health and child development. The aetiology of postpartum depressivesymptoms (PPDS) is characterised within a biopsychosocial framework, yet the underlying biologicalmechanisms remain incompletely understood. The endocannabinoid system (ECS), which interactswith the glucocorticoid system and is implicated in the pathophysiology of depressive disorders, hasnot yet been investigated in relation to PPDS. Moreover, longitudinal investigations including bothmothers and fathers and long-term measurements in hair are currently lacking.Objective: This study aimed to examine longitudinal associations between parents’ hairendocannabinoids and parental PPDS across the first two years postpartum, adjusting for hair cortisol.Secondary aims were to assess associations between parental PPDS and hair N-acylethanolamines, andto explore intergenerational links with children’s hair endocannabinoids and N-acylethanolamines.Methods: Data from 307 mothers, 208 fathers, and 288 children, who partook in the biological sub-study DREAMHAIR were used. Mothers and fathers completed the Edinburgh Postnatal DepressionScale to assess PPDS at 8 weeks, 14 months, and 24 months after birth. At each assessment, mothers,fathers, and their children provided 2 cm hair samples. Concentrations of the endocannabinoids AEAand 1-AG/2-AG, the N-acylethanolamines SEA, PEA, and OEA, as well as cortisol were quantified.Results: Multi-group random intercept cross-lagged panel models showed no significant associationsbetween PPDS and hair endocannabinoids or N-acylethanolamines in either mothers or fathers. OnlyPPDS at eight weeks after birth were associated with lower hair AEA levels at 14 months. Adjusting forhair cortisol did not alter effects. Exploratory analyses indicated that higher maternal PPDS eight weeksafter birth associated with lower child hair OEA levels at 14 months, while paternal PPDS at 14 monthsshowed a non-significant trend with higher child hair 1-AG/2-AG levels at 24 months.Conclusion: Findings suggest that rather than altered hair endocannabinoids and N-acylethanolaminespredicting PPDS, depressive psychopathology may influence AEA signalling over time in a communitycohort of mothers and fathers. Potential intergenerational effects of PPDS via the ECS require furtherexploration. Future research in high-risk samples and with a broader covariate adjustment is needed toinform possible interventive approaches.