Examining the relationship between prenatal depression, amygdala-prefrontal structural connectivity and behaviour in preschool children

Abstract

Prenatal depression is a common, underrecognized, and undertreated condition with negative consequences on child behaviour and brain development. Neurological dysfunction of the amygdala, cingulate cortex and hippocampus are associated with the development of depression and stress disorders in youth and adults. Although prenatal depression is associated with both child behaviour and neurological dysfunction, the relationship between these variables remains unclear. In this study, fiftyfour mothers completed the Edinburgh Depression Scale (EDS) during the second and third trimester of pregnancy and 3 months postpartum. Their children's behaviour was assessed using the Child Behaviour Checklist (CBCL), and the children had diffusion magnetic resonance imaging (MRI) at age 4.1 +/-0.8 years. Associations between prenatal depressive symptoms, child behaviour, and child brain structure were investigated. Third trimester EDS scores were associated with altered white matter in the amygdala-frontal tract and the cingulum, controlling for postpartum depression. Externalizing behaviour was sexually differentiated in the amygdala-frontal pathway. Altered structural connectivity between the amygdala and frontal cortex mediated the relationship between third trimester maternal depressive symptoms and child externalizing behaviour in males, but not females. These findings suggest that altered brain structure is a possible mechanism via which prenatal depressive symptoms can impact child behaviour, highlighting the importance of both recognition and intervention in prenatal depression. Introduction:Depressive symptoms affect between 13-40% of women in pregnancy [1]. Despite this, prenatal depression is under-recognized and under-treated [2,3], which can lead to poor child outcomes.Independent of postnatal depression and anxiety, prenatal depression is associated with lower child intelligence [4,5], higher infant generalized anxiety and sleep problems [6], increased internalizing and externalizing behaviour in preschool-aged children [7], and increased risk for depression at 18 years [8].Furthermore, evidence indicates that effective treatment of maternal prenatal depression improves child outcomes, for example, by decreasing internalizing behaviour [9].Child behavioural deficits associated with prenatal maternal depression might be explained, at least in part, by alterations to the underlying neurological structure and function. The stress response is regulated by the cingulate cortex, hippocampus, and amygdala [10]. Dysfunction of these brain regions is associated with the development of depression and stress disorders in youth and adults [11]. The amygdala is particularly important for emotional processing [12,13], specifically through its connections to the frontal cortex [14]. Altered connectivity between the amygdala and associated cortical areas is associated with vulnerability to depression [15][16][17][18], anxiety, and increased stress reactivity [19,20].Maternal prenatal depression may impact child behaviour by alterin...

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex‐dependent way

“…This may make them more susceptible to the negative effects of PMDS, leading to an increased likelihood of neurodevelopmental disorders. For instance, studies have found that boys who were exposed to high levels of PMDS during infancy displayed symptoms such as heightened anxiety, poorer motor skills and increased sleep disturbances (Gerardin et al, 2011; Hay et al, 2019). Whether girls or boys are more vulnerable to PMDS depends on the type, severity, timing of PMDS exposures and age of the offspring at the time of investigation (Bale et al, 2015; Glover et al, 2010).…”

Prenatal Depression Exposure Alters White Matter Integrity and Neurodevelopment in Early Childhood

“…Other researchers have found, associations of frontal functional connectivity with internalizing and externalizing behavior at 24 months following PDE(Soe et al 2016). In turn, altered structural connectivity in prefrontal-limbic pathways mediated externalizing behavior following PDE in 2-6-year-old children(Hay et al 2020). The CBCL may not be a reliable measure in our setting or at this very young age when parent reports of behavior challenges tend to be less stable.The pattern in this cohort of widespread associations of PDE with decreased white matter integrity is notable.…”

“…Diffusion tensor imaging (DTI) studies in infants with PDE have reported differences in white matter microstructural integrity of frontal and limbic regions compared to unexposed control infants (Dean et al 2018;Graham et al 2020;Rifkin-Graboi et al 2013), although not all data are consistent (Jha et al 2016). In older children (spanning 2-10 years) differences in white matter integrity have been observed in frontal, temporal and limbic regions (El Marroun et al 2018;Hay et al 2020;Lebel et al 2016). Further, altered white matter integrity of frontal-limbic networks in toddlers with PDE has been shown to predict internalizing and externalizing behaviors (Hay et al 2020;Wee et al 2017).…”

“…In older children (spanning 2-10 years) differences in white matter integrity have been observed in frontal, temporal and limbic regions (El Marroun et al 2018;Hay et al 2020;Lebel et al 2016). Further, altered white matter integrity of frontal-limbic networks in toddlers with PDE has been shown to predict internalizing and externalizing behaviors (Hay et al 2020;Wee et al 2017).…”

Exposure to Prenatal Stress Is Associated With an Excitatory/Inhibitory Imbalance in Rat Prefrontal Cortex and Amygdala and an Increased Risk for Emotional Dysregulation

“…Nonetheless, not all offspring are affected by prenatal stress (PNS), and intrinsic factors such as genetic or molecular factors can also play a critical role in determining the functional outcomes (Abbott et al, 2018). More in detail, long-lasting changes in brain regions, such as the amygdala (AMY), prefrontal cortex (PFC), and hippocampus can occur during key gestational periods and are reported in humans (Hay et al, 2019). These regions, especially the PFC and AMY, are strongly interconnected; and their work in concert is essential to regulate mood, emotions, and stress responsiveness (Murray et al, 2011;Likhtik et al, 2014).…”