Early Depression May Affect Gray Matter Development

Nancy A. Melville

January 05, 2016

Depression in early childhood is associated with reductions in gray matter development in the brain during early adolescence, with the reductions linked to the number of depressive symptoms, suggest results of a longitudinal study tracking children for up to 11 years.

"The [findings show] that the experience of early childhood depression has a material impact on the way the brain grows and develops," lead author Joan L. Luby, MD, Department of Psychiatry, the Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News.

"Based on [these findings], we should no longer ignore or fail to identify and attempt to treat early childhood depression."

Their results were published online December 16 in JAMA Psychiatry.

The study involved 193 children aged 3 to 6 years in the St. Louis area for whom behavioral and neuroimaging data were collected between September 2003 and December 2014.

Behavioral assessments taken before and at the time of the first neuroimaging scan indicated that 90 children had prevoiusly received a diagnosis of major depressive disorder (MDD).

MRI scans taken in three waves showed alterations in cortical gray matter volume loss and thinning that were significantly associated with having had an episode of MDD prior to the first imaging scan (volume loss slope estimate, -0.93 cm3; 95% confidence interval [CI], -1.75 to -0.10 cm3 per scan wave; thinning slope estimate, -0.0044 mm; 95% CI, -0.0077 to -0.0012 mm per scan wave).

"Children with depression symptom scores [that were] 2 SDs [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 explain. "Similarly, cortical thickness also decreased more rapidly at almost the same rate."

Importantly, the decreases in cortical gray matter thickness that were associated with mean depression symptom scores were bilateral, whereas volume decreases were more significant in the right hemisphere, they note.

"The absence of lateralized findings for thickness and the marginally significant finding on the left hemisphere for volume is notable given that much of the extant literature on MDD has discussed the right hemisphere," the authors write.

No significant associations were seen between gray matter development and factors that included a family history of depression or experiences of traumatic or stressful life events.

"It was surprising that the experience of depression was so powerfully predictive above other known established effects, such as poverty and maternal support, etc," Dr Luby said.

"This was the first study to report on change in gray matter across development measured at three waves, so it really is new territory," she added. "Other studies have only looked at one outcome imaging wave."

The findings are consistent with volumetric gray matter patterns in depressed adults, and Dr Luby noted that they raise the issue of plasticity and the potential effect of treatment in children and adults alike.

"There is evidence for plasticity of gray matter with intense practice of various kinds of tasks even in adults," she said.

"So [plasticity] certainly is possible based on what we know about the brain's ability to change with experience and 'exercise.' It is unknown whether treatment will impact this effect, but this is a ripe area for new investigation."

Synaptic Pruning

In an editorial that accompanied the study, Ian H. Gotlib, PhD, and colleagues agree that more research is needed to determine the role of treatment of depression in brain development during adolescence.

The study may shed light on the role of depression on issues such as synaptic pruning, Dr Gotlib told Medscape Medical News.

"The authors' finding that global volume of gray matter declines more steeply in adolescents with more severe depression suggests that synaptic pruning is particularly aggressive in individuals who have experienced symptoms of depression," said Dr Gotlib, who is the David Starr Jordan Professor and chair of the Department of Psychology at Stanford University, in California.

"It will be useful in future work to examine the relations of these cortical changes with changes in specific symptoms of depression to assess whether there is specificity in the neural underpinnings of depression in children and adolescents," he added.

This study was supported by grants from the National Institute of Mental Health, the National Institutes of Health Blueprint, and the National Institutes of Health. Dr Luby has received royalties from Guilford Press. Coauthors of the article have served in consulting relationships with Pfizer, Amgen, and Roche. Dr Gotlib has disclosed no relevant financial relationships.

JAMA Psychiatry. Published online December 16, 2015. Abstract, Editorial


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