Prenatal Depressive Symptoms are Associated With Smaller Infant Offspring Hippocampal Volume

• In Event: The Prenatal Environment and Early Experiences: Neurodevelopmental Consequences of Stress in Infants and Young Children

Abstract

Background: Offspring of women with depression are at greater risk for experiencing depression as well as other emotional difficulties. Numerous potential mechanisms have been provided to explain the intergenerational risk for depression (Gotlib, Goodman, & Humphreys, 2020). Caregiving behaviors appear to be a compelling explanation linking maternal depressive symptoms to child outcomes (Tully, Iacono, & McGue, 2008). However, if offspring vary in ways linked to depression risk prior to exposure to variation in the postnatal environmental, it would suggest that at least some risk mechanisms are likely in place prior to birth. Here we investigated whether prenatal depressive symptoms were associated with offspring amygdala and hippocampal volume, brain regions that are both linked to psychopathology in older samples.

Method: Participants were 38 mother¬–infant pairs. Women (M age=29.75, SD=5.05 years) were recruited and assessed during pregnancy; magnetic resonance imaging scans were acquired from infants (47% male) at corrected age 5 weeks (M=5.23, SD=1.35 weeks). Women completed the Edinburgh Postnatal Depression Scale (EPDS) and the Center for Epidemiologic Studies Depression Scale (CES-D) to report on depressive symptoms during pregnancy. Women also participated in interviews to report on stressful events during pregnancy (and prior to conception). Infants completed T1-weighted and T2-weighted structural scans from which amygdala and hippocampal volumes were each manually traced following standardized procedures (Hashempour et al., 2019) by one of two trained raters. Segmentations were then further edited as needed and finalized by a third rater trained in neuroanatomy. Intracranial volume was estimated by summing gray matter, white matter, and cerebrospinal fluid automatic segmentation volumes (Wang et al., 2018).

Results: Results indicated that total depressive symptoms from the EDPS were associated with smaller infant hippocampal volume, over and above ICV (B=-7.85, SD=3.48, B=-0.26 [-0.49, -0.03], t(73)=-2.26, p=.027; see Figure 1). In addition, this pattern was also found using depressive symptoms obtained from the CES-D (B=-4.08, SD=1.79, B=-0.24 [-0.45, -0.03], t(73)=-2.28, p=.026; see Figure 2). While the association between prenatal stress and infant hippocampal volume was not statistically significant, when prenatal stress was included in the model, neither measure of depressive symptoms remained a significant predictor of volume, indicating the potential for shared variance between these prenatal characteristics. Amygdala volume was not associated with either depressive symptoms or stressful experiences assessed during pregnancy.

Conclusion: We find evidence that prenatal depressive symptom severity is linearly associated with smaller infant hippocampal volume assessed at age 5 weeks. Though there are several possible prenatal influences (i.e., genetic or environmental factors) that may contribute to these associations, it is unlikely that these associations are better explained by postnatal caregiving, given the young age of the infants in this study. Our findings indicate prenatal detection and treatment of depressive symptoms may be an important target to not only improve maternal mood and well-being and also to potentially benefit the developing fetus.

Authors

• Kathryn L. Humphreys, Vanderbilt University
  Presenting Author

• M. Catalina Camacho, Washington University in St. Louis
  Non-Presenting Author

• Vikas Dodda, Vanderbilt University
  Non-Presenting Author

• Sydney Takemoto, Vanderbilt University
  Non-Presenting Author

• Marissa C. Roth, Vanderbilt University
  Non-Presenting Author