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J Am Acad Child Adolesc Psychiatry. 2015 Apr;54(4):313-21.e2. doi: 10.1016/j.jaac.2015.01.013. Epub 2015 Jan 30.

Antenatal maternal anxiety predicts variations in neural structures implicated in anxiety disorders in newborns.

Author information

Singapore Institute for Clinical Sciences.
Singapore Institute for Clinical Sciences; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute and Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal.
KK Women's and Children's Hospital, Singapore.
Clinical Imaging Research Centre, National University of Singapore.
Yong Loo Lin School of Medicine.
Singapore Institute for Clinical Sciences; Yong Loo Lin School of Medicine, National University of Singapore, and National University Health System, Singapore.
Singapore Institute for Clinical Sciences; Yong Loo Lin School of Medicine.
Singapore Institute for Clinical Sciences; Liggins Institute, University of Auckland, New Zealand.
Singapore Institute for Clinical Sciences; National University of Singapore. Electronic address:



Antenatal maternal anxiety predicts offspring neurodevelopment and psychopathology, although the degree to which these associations reflect postnatal influences is unclear. To limit this possibility, we assessed newborn neuronal microstructures using diffusion tensor imaging (DTI) and assessed neonatal microstructure variation in relation to antenatal anxiety and in prediction of infant socio-emotional behavior at age 1 year.


Dyads were drawn from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort, and included mothers who completed the Speilberger State-Trait Anxiety Inventory (STAI) at 26 weeks gestation (scoring >90, n = 20; scoring <70, n = 34) and their neonates (5-17 days postnatal) who took part in DTI.


Antenatal anxiety predicted variation in fractional anisotropy (FA) of regions important to cognitive-emotional responses to stress (i.e., the right insula and dorsolateral prefrontal cortex), sensory processing (e.g., right middle occipital), and socio-emotional function (e.g., the right angular gyrus, uncinate fasciculus, posterior cingulate, and parahippocampus). In a subset of infants with Infant Toddler Socio-Emotional Assessment (ITSEA) data, some of these right lateralized clusters predicted infant internalizing (e.g., insula: β = 0.511, p = .03) but not externalizing behavior 1 year later, although these analyses failed to withstand the correction for multiple comparisons.


These findings suggest the need for larger-scale investigations of the role that corticolimbic structures play in regulating cognitive-emotional responses to threat, and potentially in mediating the cross-generational transmission of anxiety, as well as in underscoring the importance of early mother-infant intervention programs.


antenatal anxiety; axial diffusivity; diffusion tensor imaging; fractional anisotropy; neonatal brain

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