Early-Life Depression May Alter Brain Development, Study Suggests

The brains of children diagnosed with major depressive disorder early in life may develop differently from those of children unaffected by the disorder, suggests a study published Wednesday in JAMA Psychiatry.

Early in childhood, the brain experiences rapid neurogenesis and related increases in gray matter volume, followed by a process of selective elimination and myelination in early puberty, resulting in volume loss and thinning. The findings of the current study suggest that children who experience depression early in life may experience steeper declines in cortical gray matter volume and thickness over the course of development compared with those who have no history of depression early in life.

Joan Luby, M.D., a professor of child psychiatry at Washington University School of Medicine, and colleagues analyzed data collected from 193 children aged 3 to 6 (including 90 diagnosed with MDD) who underwent behavioral assessments and multiple MRI scans as they aged into early adolescence. A total of 116 children received three waves of neuroimaging scans (the first wave scans took place when the children were under 9, and final scans were taken when the children were 12 to 15).

The scans revealed marked decreases in thickness of cortical gray matter and in the volume of the right hemisphere (with marginal significance on the left hemisphere) associated with mean level of depression symptom scores and MDD diagnosis experienced from preschool to school age. Children with depression symptom scores two standard deviations above the mean had a reduction in volumes of gray matter at almost twice the rate of those with no childhood depression symptoms. Similarly, cortical thickness also decreased more rapidly at almost the same rate.

“The study findings … provide the first data, to our knowledge, demonstrating depression-related alterations in volume and thickness of cortical gray matter evident as early as middle childhood,” the researchers wrote. “Whether these early alterations serve as an endophenotype of risk for later depressive episodes or chronic course is a question of interest as the study sample is followed up through adolescence.”

In a related editorial that describes several ways that longitudinal neuroimaging research can inform the understanding of psychiatric disorders, Ian Gotlib, Ph.D., and Sarah Ordaz, Ph.D., of Stanford University offered multiple questions raised by Luby's study: “Does each depressive episode alter neural trajectories and increase the likelihood of subsequent depressive episodes? Do trajectories change more markedly through puberty? How can peers, parents, and treatments counteract maladaptive developmental trajectories?”

They concluded, “We now have the analytic tools to answer these and other questions; the next few years promise to yield information that we can use to determine how best to treat and, ultimately, prevent the occurrence of brain-based disorders.”