Maternal depression and the polygenic p factor: A family perspective on direct and indirect effects

Abstract

Within-family studies typically assess indirect genetic effects of parents on children, however social support theory points to a critical role of partners and children on women's depression. To address this research gap and account for the high heterogeneity of depression, we calculated a general psychiatric factor using eleven major psychiatric polygenic scores (polygenic p), in up to 25,000 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study (MoBa). Multilevel modelling of trio polygenic p was used to distinguish direct and indirect genetic effects on mother’s depression during pregnancy (gestational age 17 and 30 weeks), infancy (6 months, 18 months) and early childhood (3 years, 5 years, and 8 years). We found mother’s polygenic p predicts their depression symptoms (b= 0.092; 95% CI [0.087,0.098]), outperforming prediction using a single major depressive disorder polygenic score (b= 0.070, 95% CI [0.066,0.075]). Jointly modelling trio polygenic p revealed indirect genetic effects of fathers (b = 0.022, 95% CI [0.014,0.030]) and children (b = 0.021, 95 % CI [0.010,0.037]) on mothers' depression and a negative interaction between child genes and time (b = -0.024, 95% CI [-0.045,0.004]), indicating the effect of time on depression differs as a function of child liability to psychiatric disorders. Our results support the generalizability of polygenic effects across mental health and highlight the importance of incorporating longitudinal data into our within-family analyses.

Disentangling direct and indirect genetic effects from partners and offspring on maternal depression using trio-GCTA

“…Our findings are broadly in line with the conceptualisation of maternal depression as a family-wide mental illness 9,49 , the risk of which is influenced both by individual factors (e.g., direct genetic effects), and family-level characteristics, as has been shown previously 50 . The results of the present study suggest that genetic effects from both partners and offspring, mediated through the environment, contribute to maternal depressive symptoms at multiple timepoints after birth.…”

Intergenerational consequences of racism in the United Kingdom: a qualitative investigation into parents' exposure to racism and offspring mental health and well‐being

“…Participants discussed parent and child experiences of racism as intrinsically connected and co‐occurring, with vicarious consequences in both directions between generations (Figure 2). Our data corroborate the hypothesis that parents' experiences of racism can impact child well‐being in the United Kingdom, while further highlighting a broader bidirectional picture, as raised previously in research on racism exposure (Colen et al., 2019) and family mental health (Ahmadzadeh et al., 2019; Ayorech et al., 2023; Creswell et al., 2020). Results emphasise the pervasive nature of racism for some families in Britain, the impacts of which may vary by individuals' intersecting identities (Crenshaw, 1989) and the need for a family systems approach to understanding the impacts (Cox & Paley, 2003).…”

“…The same was true for results relating to child social behaviour, including social isolation and low self‐confidence. As outlined in family mental health causal inference research, it could be that children's internalising symptoms go on to impact parents' mental health and behaviour (Ahmadzadeh et al., 2019; Ayorech et al., 2023; Creswell et al., 2020), as the mechanism for indirect effects of children's experiences of racism on parents (Figure 2). Parents did not discuss children's externalising‐related behaviours, although teenagers described their own anger and frustration, sometimes directed towards their parents.…”

“…Research has been based on brief, broad measures of parents' exposure to interpersonal and some institutional forms of racism, with child outcomes examined across all stages of development. The possibility of child experiences of racism impacting parents has been considered by very few (Colen, Li, Reczek, & Williams, 2019), which could involve children's mental health impacting parents' mental health and behaviour, as identified in family mental health causal inference research (Ahmadzadeh et al., 2019; Ayorech et al., 2023; Creswell et al., 2020). Most studies have been focussed on experiences in African American families in the United States, with some including Mexican and Chinese American families, or indigenous families in Australia and New Zealand.…”