Molecular Psychiatry: Associations Among White Matter Microstructural Changes and the Development of Emotional Reactivity and Regulation in Infancy

In infancy and throughout childhood, high levels of negative emotionality (for example, frequent and intense crying), low levels of positive emotionality (for example, limited smiling and laughter), and deficits in emotional regulation can predict future behavioral and affective disorders. White matter tracts in the brain develop rapidly in the first postnatal year, and their development is critical for establishing the neural architecture supporting optimal regulation of emotional behavior.

A team of scientists led by Mary L. Phillips, MD, MD (Cantab) (Pittsburgh Foundation-Emmerling Endowed Chair in Psychotic Disorders and Distinguished Professor of Psychiatry, Bioengineering, and Clinical and Translational Science) and Alison Hipwell, PhD, PsyD (Professor of Psychiatry and Psychology) examined the development of white matter microstructure in infants ages three to nine months old to understand the neural mechanisms underlying emotional reactivity and emotional regulation issues that may precede behavioral and emotional problems later in life. From the University of Pittsburgh, the team additionally included first author Yicheng Zhang, PhD (former doctoral student in Dr. Phillips’s lab), Layla Banihashemi, PhD (Associate Professor of Psychiatry and Bioengineering), and Amelia Versace, MD (Associate Professor of Psychiatry).

In a study published in Molecular Psychiatry, the investigators reported findings that larger three-to-nine-month changes in white matter structure in the right uncinate fasciculus, forceps minor, and left cingulum bundle were associated with larger decreases or smaller increases in soothability and positive emotionality during this period. 

“Our findings show that the brain's structural organization in early infancy lays the foundation for early emotional development. Identifying these early neural markers has the potential to improve early risk detection and help with targeted interventions during critical developmental windows, to transform how we approach infant mental health,” said Dr. Phillips, senior author of the study.

Associations among white matter microstructural changes and the development of emotional reactivity and regulation in infancy
Zhang Y, Banihashemi L, Versace A, Samolyk A, Abdelkader M, Taylor M, English G, Schmithorst VJ, Lee VK, Stiffler R, Aslam H, Panigrahy A, Hipwell AE, Phillips ML.
Molecular Psychiatry 30, 3168–3174 (2025). https://doi.org/10.1038/s41380-025-03025-w