Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 18:19:1603022.
doi: 10.3389/fnhum.2025.1603022. eCollection 2025.

Brain white matter development in 8-year-old children is associated with maternal mental health during pregnancy

Yali Huang  1 , Timothy R Koscik  2   3 , Aline Andres  2   4 , Jayne Bellando  2   4 , Charles M Glasier  1   2 , Adhitya Ram  5 , Xiawei Ou  1   2   3   4
Affiliations

Brain white matter development in 8-year-old children is associated with maternal mental health during pregnancy

Yali Huang et al. Front Hum Neurosci. .

Abstract

Background: Maternal mental health during pregnancy can influence fetal brain development, yet its long-term effects remain unclear. This study investigates the association between prenatal maternal depression and anxiety symptoms and white matter microstructure in the limbic system of 8-year-old children.

Methods: Fifty-one healthy pregnant women and typically developing 8-year-old children dyads were included in this prospective and longitudinal study. Maternal depression and anxiety symptoms were assessed at 12, 24, and 36 weeks of gestation using the Beck Depression Inventory-II (BDI-II) and State-Trait Anxiety Inventory (STAI). Their children underwent a brain MRI examination at age 8 years with multi-shell diffusion imaging analyzed using diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI) models for a multi-aspect evaluation of microstructural development. Key diffusion metrics (FA: fractional anisotropy; MD: mean diffusivity; AD: axial diffusivity; RD: radial diffusivity; MK: mean kurtosis; AK: axial kurtosis; RK: radial kurtosis; NDI: neurite density index; ODI: orientation dispersion index; FWF: free water fraction) were extracted from the limbic system white matter structures including cingulum, fornix, and uncinate fasciculus, which are closely associated with emotional and motivational processes.

Results: Higher maternal depression symptom scores were associated with lower FA (R = -0.3126, p = 0.0305, in CGH.R; R = -0.3025, p = 0.0366, in FXC.R) and MK (R = -0.3284, p = 0.0227, in CGG.R) and higher MD (R = 0.2879, p = 0.0472, in CGH.R) and RD (R = 0.3451, p = 0.0163, in CGH.R; R = 0.3456, p = 0.0161, in FXC.R) in predominately right-hemisphere limbic tracts. Higher maternal anxiety symptom scores were associated with increased MD (R = 0.2897, p = 0.0458, in FXC.L; R = 0.2859, p = 0.0488, in UF.L) and RD (R = 0.3168, p = 0.0283, in FXC.L), decreased NDI (R = -0.3787, p = 0.0079, in FXC.L; R = -0.3422, p = 0.0173, in UF.R), and increased AK (R = 0.3154, p = 0.029, in UF.L) in predominately left-hemisphere limbic tracts.

Conclusion: Our findings suggest that maternal depression and anxiety during pregnancy may have long-lasting impacts on offspring white matter microstructure maturation in the limbic system. This highlights the need for prenatal mental health screening and potential interventions to promote brain development and support optimal neurodevelopmental outcomes in children.

Keywords: children’s neurodevelopment; diffusion kurtosis imaging (DKI); diffusion tensor imaging (DTI); limbic system white matter; neurite orientation dispersion and density imaging (NODDI); prenatal maternal mental health.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Maternal depression symptom scores (measured by BDI) and anxiety symptom scores (measured by STAI) during the 3 pregnancy trimesters (T1, T2, and T3).
Figure 2
Figure 2
The white matter regions of interest in the limbic system. CGG: Cingulum (cingulate gyrus); CGH: Cingulum (hippocampus); fornix (FNX); uncinate fasciculus (UF). The definitions of these regions come from the JHU atlas.
Figure 3
Figure 3
Significant correlation between maternal depression symptom scores (measured by BDI) during the 3 pregnancy trimesters (T1, T2, and T3) and children brain diffusion imaging parameters (measured by DTI) at age 8 years.
Figure 4
Figure 4
Significant correlation between maternal depression symptom scores (measured by BDI) during the 3 pregnancy trimesters (T1, T2, and T3) and children brain diffusion imaging parameters (measured by DKI) at age 8 years.
Figure 5
Figure 5
Significant correlation between maternal depression symptom scores (measured by BDI) during the 3 pregnancy trimesters (T1, T2, and T3) and children brain diffusion imaging parameters (measured by NODDI) at age 8 years.
Figure 6
Figure 6
Significant correlation between maternal anxiety symptom scores (measured by STAI) during the 3 pregnancy trimesters (T1, T2, and T3) and children brain diffusion imaging parameters (measured by DTI) at age 8 years.
Figure 7
Figure 7
Significant correlation between maternal anxiety symptom scores (measured by STAI) during the 3 pregnancy trimesters (T1, T2, and T3) and children brain diffusion imaging parameters (measured by DKI) at age 8 years.
Figure 8
Figure 8
Significant correlation between maternal anxiety symptom scores (measured by STAI) during the 3 pregnancy trimesters (T1, T2, and T3) and children brain diffusion imaging parameters (measured by NODDI) at age 8 years.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Avants B. B., Tustison N., Song G. (2009). Advanced normalization tools (ANTS). Insight J. 2, 1–35. doi: 10.54294/uvnhin - DOI
    1. Bano W., Pulli E., Cantonas L., Sorsa A., Hämäläinen J., Karlsson H., et al. (2024). Implementing ABCD studyⓇ MRI sequences for multi-site cohort studies: practical guide to necessary steps, preprocessing methods, and challenges. MethodsX 12:102789. doi: 10.1016/j.mex.2024.102789, PMID: - DOI - PMC - PubMed
    1. Beck A. T., Steer R. A., Brown G. (1996). Beck depression inventory–II. United States: Psychological assessment.
    1. Belden A. C., Barch D. M., Oakberg T. J., April L. M., Harms M. P., Botteron K. N., et al. (2015). Anterior insula volume and guilt: neurobehavioral markers of recurrence after early childhood major depressive disorder. JAMA Psychiatry 72, 40–48. doi: 10.1001/jamapsychiatry.2014.1604, PMID: - DOI - PMC - PubMed
    1. Blackmon K., Barr W. B., Carlson C., Devinsky O., DuBois J., Pogash D., et al. (2011). Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety. Psychiatry Res. Neuroimaging 194, 296–303. doi: 10.1016/j.pscychresns.2011.05.007, PMID: - DOI - PMC - PubMed

LinkOut - more resources