Depression in Children May Affect Gray Matter Development

Major depression may influence the course of gray matter development in children from preschool age through early adolescence, according to research in JAMA Psychiatry.

In a longitudinal study, Joan L. Luby, MD, and her colleagues at the Washington University School of Medicine in St. Louis identified “marked bilateral decreases in thickness of cortical gray matter and in volume of the right hemisphere (with marginal significance on the left hemisphere)” in children with depression.

“Children with depression symptom scores two standard deviations above the mean had reduction in volumes of gray matter at almost twice the rate of those with no childhood depression symptoms,” the authors reported. “Similarly, cortical thickness also decreased more rapidly at almost the same rate.”

The researchers tracked 193 children, including 90 with major depressive disorder, for 11 years starting in 2003. The children, ages 3 to 6 at baseline, underwent IQ testing, two psychiatric interviews (with parent report) and at least one of three waves of neuroimaging; 116 children completed all three. Structural MRI measured the volume, thickness and surface area of cortical gray matter in each child.

The children’s gray matter volume trajectories overall followed a typical course of an initial increase followed by thinning and volume loss. Global cortical gray volume in children who qualified for an MDD diagnosis, however, decreased 1.8 times faster between the first and third scans than in children with no depressive symptoms. No associations emerged between gray matter development and stressful life events or a family history of depression.

Though limited by the inability to separate developmental timing effects, the findings offer evidence for the hypothesis “that cortical thinning evident in depression begins in childhood,” the authors wrote.

“It is possible that the initial depressive episode in the participants in the study triggered a set of biological processes that kindled the development of subsequent depressive episodes in response to life stressors,” wrote Ian H. Gotlib, PhD and Sarah J. Ordaz, PhD, of Stanford University in an accompanying editorial. “It is likely that there are many pathologic processes that lead to depression. Longitudinal neuroimaging studies can answer important questions about heterogeneity in these processes and in etiologic pathways to disorder.”

Longitudinal neuroimaging research can also potentially elucidate how external factors — particularly parenting and peer interaction — influence neural trajectories and by “clarifying critical changes during specific sensitive developmental periods,” Gotlib and Ordaz wrote.


Luby JL, et al. Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.2356.

Gotlib IH and Ordaz SJ. The Importance of Assessing Neural Trajectories in Pediatric Depression. Editorial. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.2453.