Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure

Abstract

IMPORTANCE Maternal depression and anxiety can have deleterious and lifelong consequences on child development. However, many aspects of the association of early brain development with maternal symptoms remain unclear. Understanding the timing of potential neurobiological alterations holds inherent value for the development and evaluation of future therapies and interventions. OBJECTIVE To examine the association between exposure to prenatal maternal depression and anxiety symptoms and offspring white matter microstructure at 1 month of age. DESIGN, SETTING, AND PARTICIPANTS This cohort study of 101 mother-infant dyads used a composite of depression and anxiety symptoms measured in mothers during the third trimester of pregnancy and measures of white matter microstructure characterized in the mothers' 1-month offspring using diffusion tensor imaging and neurite orientation dispersion and density imaging performed from October 1, 2014, to November 30, 2016. Magnetic resonance imaging was performed at an academic research facility during natural, nonsedated sleep. MAIN OUTCOMES AND MEASURES Brain mapping algorithms and statistical models were used to evaluate the association between maternal depression and anxiety and 1-month infant white matter microstructure as measured by diffusion tensor imaging and neurite orientation dispersion and density imaging findings. RESULTS In the 101 mother-infant dyads (mean [SD] age of mothers, 33.22 [3.99] years; mean age of infants at magnetic resonance imaging, 33.07 days [range, 18-50 days]; 92 white mothers [91.1%]; 53 male infants [52.5%]), lower 1-month white matter microstructure (decreased neurite density and increased mean, radial, and axial diffusivity) was associated in right frontal white matter microstructure with higher prenatal maternal symptoms of depression and anxiety. Significant sex × symptom interactions with measures of white matter microstructure were also observed, suggesting that white matter development may be differentially sensitive to maternal depression and anxiety symptoms in males and females during the prenatal period. CONCLUSIONS AND RELEVANCE These data highlight the importance of the prenatal period to early brain development and suggest that the underlying white matter microstructure is associated with the continuum of prenatal maternal depression and anxiety symptoms.

Maternal Prenatal Stress Is Associated With Altered Uncinate Fasciculus Microstructure in Premature Neonates

“…Furthermore, while maternal anxiety can be a common proxy for stress, experiencing stressful life events during pregnancy does not always coincide with elevated scores on anxiety scales (1). Previous studies reporting associations between maternal antenatal anxiety and infant brain development have focused on state, rather than trait, anxiety (20) or a combined score of state and trait anxiety (21), while those focusing on trait anxiety alone reported no significant associations with brain development (18).…”

“…Reduced FA in white matter areas including the uncinate fasciculus has been observed in infants of highly anxious mothers (21,75). Dean et al (20) reported higher diffusivity (increased MD, RD, and AD) in the right frontal white matter of term infants born to mothers experiencing high prenatal symptoms of depression and anxiety.…”

Perinatal exposure to fluoxetine and maternal adversity affect myelin-related gene expression and epigenetic regulation in the corticolimbic circuit of juvenile rats

“…Nevertheless, our results provide a potential molecular mechanism for findings of altered brain connectivity in humans after exposure to maternal SSRI use [25][26][27] or depressive symptoms during gestation [29][30][31] . As outlined in the introduction, human studies often observe similar neurodevelopmental outcomes in children exposed to SSRIs as in children exposed to unmedicated depression, evoking questions about the source of the effects.…”

“…It is known that the severity of antenatal depressive symptoms correlates to connectivity in brain networks involved in emotion regulation in infants 29 . Several studies report sex differences 30 , with girls showing stronger associations of prenatal exposure to depressive symptoms with functional connectivity in emotion-regulation networks 31 , right amygdala volume 32 , and cortical thickness 33 than boys. Overall, prenatal exposure to SSRIs and maternal depression affect the developing brain in overlapping-but potentially also in distinct brain regions 34 , with a key role for corticolimbic structures such as the prefrontal cortex and the amygdala 25,35,36 .…”

Effects of Prenatal Mindfulness-Based Childbirth Education on Child-Bearers’ Trajectories of Distress: A Randomized Control Trial

“…To address effects on child-bearers' total distress, a distress composite score of the STAIT, CESD, and PSS was created at each wave. This combination was found to be justi ed by correlations among the measures (r = .56-.90; see Table 1) and internal reliability of the composite score, which was created by standardizing and then averaging the scores (similar to composites made for other investigations of internalizing symptoms in the perinatal period; Dean et al, 2018).…”