Maternal distress in the postpartum period, consisting of symptoms of anxiety and/or depression, is prevalent in 10-25% of pregnancies and is associated with reduced or dysregulated mother-infant bonding, representing a significant stressor to the infant (Essex et al., 2002; Lebel et al., 2020; Thomas et al., 2017). In turn, postnatal maternal distress poses risks to the emotional development of the offspring and is associated with a range of adverse emotional outcomes that may persist across the lifespan, such as internalizing and externalizing behavioral problems (Rees et al., 2019; Stein et al., 2014; Zou et al., 2019). Internalizing behavioral problems may include anxious, depressed, or withdrawn behaviors that affect one's internal environment (Liu et al., 2004). In contrast, external behavioral problems may include disruptive or aggressive behaviors that affect one's external environment (Liu et al., 2004).

Emotional regulation, defined as the ability to modulate emotional responses, including intensity, duration, or occurrence using age-appropriate strategies, is important for long-term emotional development (Blanchard-Fields & Coats, 2008; Blandon et al., 2008; Cai et al., 2021). Emotional regulation emerges in the first few months of life and continues to mature across the lifespan (Aktar & Pérez-Edgar, 2020; Rutherford et al., 2015). However, infancy through to early childhood is a sensitive period for its development (Aktar & Pérez-Edgar, 2020). During this time, emotion regulation is learned or achieved within the context of caregiver-child interactions. Disruptions in these interactions, such as lower-quality interactions or decreased sensitivity, have been observed in mothers experiencing maternal distress and can adversely affect an infant's emotional development (Feldman., 2003; Thomas et al., 2017), increasing the risk of internalizing and externalizing disorders (Crugnola et al., 2016; Feng et al., 2008; Granat et al., 2017; Maughan et al., 2007). Previous work suggests that high-quality maternal-infant interactions help to regulate the infants stress response and thus support healthy brain development (Center on the Developing Child, 2009; Donnici et al., 2021; National Scientific Council on the Developing Child, 2014). However, low-quality interactions, characterized by decreased sensitivity and negative affect which have been observed in cases of maternal distress, may leave the infant's stress response unregulated (Donnici et al., 2021; Feldman et al., 2003; Kaitz et al., 2009; Thomas, 2017).

Alterations in brain development may underlie associated risks to emotional development in offspring exposed to maternal distress (Lean, 2021). Infancy is a sensitive period for neural development. The brain undergoes rapid and complex structural and functional changes leaving developmental trajectories vulnerable to early experiences. In line with this, evidence suggests maternal distress may alter brain development in infants. For example, postnatal maternal anxiety and depression have been associated with amygdala volume in children (Donnici et al., 2021; Lupien et al., 2011). Furthermore, postnatal maternal anxiety has been negatively associated with left hippocampal volumes in infants (Qiu et al., 2013). However, associations between maternal distress and the developing infant brain have not been fully elucidated, with previous work focusing mainly on limbic structures. As such, research on infant subcortical structures more broadly in association with maternal distress is needed to identify potential early neural markers of risk.

Previous work has found variations in brain structure to predict developing emotional capabilities such as emotional regulation (Graham et al., 2017; Luby et al., 2016; Moog et al., 2021; Pagliaccio et al., 2014). For example, research has found associations between macrostructure (volume) of limbic areas and later emotion regulation at different stages of development from infants to adolescence (Blanton et al., 2010; Moog et al., 2021; Pagliaccio et al., 2014). This may suggest brain-behavior relationships may be useful predictors of emotional development. However, potential relationships between brain structure and subsequent emotional capabilities early in development during infancy have been limited. Previous research has emphasized the importance of infancy through to early childhood for emotional development, and indicates early interventions are key to promote healthy outcomes, as such, further research in elucidating neural markers to identify those at risk during this developmental period is needed.

Evidence suggests that biological sex of the infants should be considered in examination of these brain-behavior relationships. Sex differences have been found in emotional development including emotion regulation, as well as vulnerability to emotion-related pathologies (Chaplin & Aldao, 2013; Stein et al., 2014; Weinburg & Tronick, 1999). For example, internalizing disorders are more prevalent in girls, while externalizing disorders are more common in boys, both generally and in association with maternal distress (Chaplin et al., 2019; Hick et al., 2019). Together, these results suggest biological sex should be considered in examining relationships between brain structure and predictors of emotional development (Letourneau et al., 2019).

Given the evidence that infancy is a key period for brain development and maternal interactions are essential for healthy emotional development, in the present work we sought to better understand the associations between maternal distress, infant brain development and subsequent emotion regulation to identify risk and resilience factors. We hypothesized that high-quality maternal interactions support heathy brain development of the offspring. Low-quality interactions, characterized by decreased sensitivity and negative affect as observed in cases of maternal distress, may alter developing neural systems and could underlie the risks to emotional development (Feldman et al., 2003; Kaitz et al., 2009; Thomas, 2015). Furthermore, given sex-differences in the vulnerability to emotional outcomes, we hypothesized that biological sex would be an important moderator of this relationship. Based on previous findings, we hypothesized that postnatal maternal distress would be associated with infant subcortical macrostructure. We further predicted that infant subcortical macrostructure would be associated with emotion regulation abilities. Moreover, we hypothesized this association would be moderated by biological sex.

Infants underwent MRI scanning between 2-5 months of age. Subcortical brain structure volumes were extracted from anatomical MRI images. During this period (2-5 months postpartum), maternal distress was measured via self-report on anxiety and depression questionnaires. Infant emotion regulation was subsequently assessed at 8-11 months via maternal report. This study addressed the following questions: What is the association between postnatal maternal distress and infant subcortical macrostructure? Does infant subcortical macrostructure predict emotional regulation in infants in the first year of life? Does biological sex moderate this relationship?