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. 2018 Oct 1;172(10):973-981.
doi: 10.1001/jamapediatrics.2018.2132.

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

Douglas C Dean 3rd  1 , Elizabeth M Planalp  1   2 , William Wooten  3 , Steven R Kecskemeti  1 , Nagesh Adluru  1 , Cory K Schmidt  1   3 , Corrina Frye  3 , Rasmus M Birn  4   5 , Cory A Burghy  3 , Nicole L Schmidt  1 , Martin A Styner  6   7 , Sarah J Short  3 , Ned H Kalin  1   2   5 , H Hill Goldsmith  1   2 , Andrew L Alexander  1   4   5 , Richard J Davidson  1   2   3   5
Affiliations

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

Douglas C Dean 3rd et al. JAMA Pediatr. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kalin reported receiving honoraria from CME Outfitters, Elsevier, and the Pritzker Neuropsychiatric Disorders Research Consortium; serving on the advisory boards for Corcept Therapeutics and Skyland Trail–George West Mental Health Foundation; and being a stockholder in Corcept Therapeutics and owning the following patents: promoter sequences for corticotropin-releasing factor alpha (US patent 7071323, issued on July, 4, 2006), a method of identifying agents that alter the activity of the promoter sequences (US patent 7531356, issued on May 12, 2009), promoter sequences for urocortin II and the use thereof (US patent 7087385, issued on August 8, 2006), and promoter sequences for corticotropin-releasing factor binding protein and use thereof (US patent 7122650, issued on October 17, 2006). Dr Davidson reported being the founder and president and serving on the board of directors for the nonprofit organization Healthy Minds Innovations Inc and serving on the board of directors for the Mind & Life Institute. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Prenatal Maternal Depression and Anxiety Symptoms and Infant Brain Diffusivity
Magnetic resonance imaging shows voxelwise associations between prenatal maternal depression and anxiety composite and radial diffusivity (RD) (top), mean diffusivity (MD) (middle), and axial diffusivity (AD) (bottom), with increased RD, MD, and AD in right-hemispheric white matter. Scale indicates cluster-corrected P values.
Figure 2.
Figure 2.. Association of Increased Prenatal Maternal Depression and Anxiety Symptoms With Decreased Infant Neurite Density
Neurite orientation dispersion and density imaging intracellular volume fraction revealed white matter–spanning bilateral regions of the prefrontal cortex, including white matter of the superior, middle, and inferior frontal gyrus and the anterior and superior corona radiata, that was negatively associated with the prenatal maternal depression and anxiety symptom composite. VIC indicates intracellular volume fraction. Scale indicates cluster-corrected P values.
Figure 3.
Figure 3.. Association of Prenatal Maternal Depression and Anxiety Symptoms With Brain Microstructure in Males vs Females
Fractional anisotropy (FA) (A and D), neurite orientation dispersion and density imaging (NODDI) intracellular volume fraction (VIC) (B and E), and orientation dispersion index (ODI) (C and F) were observed to be differentially associated with prenatal maternal adversity in the white matter of males and females, with associations localized within left-hemisphere white matter, including superior-frontal white matter, corona radiata, and splenium of the corpus callosum. Representative plots depict this differing association between males and females, with scatterpoints corresponding to individual mean criteria (FA, VIC, and ODI) and the solid lines corresponding to the lines of best fit with prenatal maternal depression and anxiety symptoms composite. DTI indicates diffusion tensor imaging.
See this image and copyright information in PMC

References

    1. Bennett HA, Einarson A, Taddio A, Koren G, Einarson TR. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol. 2004;103(4):698-709. doi:10.1097/01.AOG.0000116689.75396.5f - DOI - PubMed
    1. Evans J, Melotti R, Heron J, et al. . The timing of maternal depressive symptoms and child cognitive development: a longitudinal study. J Child Psychol Psychiatry. 2012;53(6):632-640. doi:10.1111/j.1469-7610.2011.02513.x - DOI - PubMed
    1. Heron J, O’Connor TG, Evans J, Golding J, Glover V; ALSPAC Study Team . The course of anxiety and depression through pregnancy and the postpartum in a community sample. J Affect Disord. 2004;80(1):65-73. doi:10.1016/j.jad.2003.08.004 - DOI - PubMed
    1. Biaggi A, Conroy S, Pawlby S, Pariante CM. Identifying the women at risk of antenatal anxiety and depression: a systematic review. J Affect Disord. 2016;191:62-77. doi:10.1016/j.jad.2015.11.014 - DOI - PMC - PubMed
    1. Kinsella MT, Monk C. Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. Clin Obstet Gynecol. 2009;52(3):425-440. doi:10.1097/GRF.0b013e3181b52df1 - DOI - PMC - PubMed

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