Pediatric Depression Linked to Loss of Grey Matter

Early childhood depression is associated with decreased cortical gray matter volume and thickness over time, according to study results published in JAMA Psychiatry.

The trajectory of gray matter development is not fully understood, but is known to increase in volume secondary to neurogenesis during early childhood, peaking early on in puberty then losing volume and thickness through selective elimination later. It is influenced by many factors including IQ, genetics, psychosocial factors, sex, and puberty status. Further, decreased cortical gray matter has been reported in adult patients with depression; however, it is unknown how childhood depression influences gray matter development.

Joan Luby, MD of the Department of Psychiatry at Washington University School of Medicine in St. Louis, MO and colleagues conducted a longitudinal neuroimaging and behavioral study of 193 children aged 3 to 6 years from September 2003 to December 2014. Participants were assessed with psychiatric interviews and magnetic resonance imaging (MRI) scans to understand the impact of depression on the trajectory of gray matter development.

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In total, 90 of 193 participants had major depression. The P-SA-MDD score, which was calculated to include depression symptoms from preschool to school age, was significantly different in depressed patients compared to those without depression.The authors noted that over time, cortical gray matter volume significantly decreased at a rate consistent with normal reductions (slope estimate= -7.80, SE=0.61, t=-12.73, P<0.001). Further, models in participants with depression demonstrated alterations in both cortical thinning (slope estimate=-0.0044, SE=0.0016, t=-2.72, P=0.007) and gray matter volume loss (slope estimate=-0.93, SE=0.42, t=-2.21, P=0.03). Traumatic or stressful childhood events or a family history of depression did not have significant associations with gray  matter development.

“Children with depression symptom scores 2 SDs above the mean had reduction in volumes of gray matter at almost twice the rate of those with no childhood depression symptoms,” The authors wrote.

Although the study was not designed to determine the exact cause of the cortical changes, the authors hypothesize that these changes could be related to “experience-dependent neuroplasticity”.1

In an accompanying editorial, Ian Gotlib, PhD, of the Department of Psychology and Sara Ordaz, PhD, of the Department of Psychiatry at Stanford University in California noted that longitudinal neuroimaging studies can improve our understanding of how external factors affect the development of psychiatric disorders, the effects of changes during sensitive periods of development, and the pathways to developing a psychiatric disorder.

Furthermore, they emphasized the importance of research into understanding the effects of depression treatment on brain development in order to find the best time to treat.2


  1. Luby JL, Belden AC, Jackson JJ, 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.
  2. Gotlib IH, Ordaz SJ. The Importance of Assessing Neural Trajectories in Pediatric Depression. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.2453.