Anxious/depressed symptoms are linked to right ventromedial prefrontal cortical thickness maturation in healthy children and young adults

Abstract

The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant "CBCL Anxious/Depressed by Age" interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (<9 years), but positively associated with thickness at older ages (15-22 years), with the shift in polarity occurring around age 12. This was secondary to a slower rate of vmPFC cortical thinning in subjects with higher scores. In young adults (18-22 years), Anxious/Depressed scores were also positively associated with precuneus/posterior cingulate cortical thickness. Potential neurobiological mechanisms underlying this maturation pattern are proposed. These results demonstrate the dynamic impact of age on relations between vmPFC and negative affect in the developing brain.

Keywords: Child Behavior Checklist; anxiety; brain development; depression; magnetic resonance imaging.

Figure 1.

Brain areas where local cortical thickness is associated with the CBCL Anxious/Depressed score by Age interaction when controlling for gender, scanner, and total brain volume (n = 533 scans). Right midsagittal view on top and ventral view at the bottom. The peak is at MNI coordinates x = 2.1, y = 35.6, z = −23.4, which is located in the right gyrus rectus. Brain areas not shown in this figure were not significant. Figure is shown at P ≤ 0.05 with a whole-brain random field theory correction. Blue shades correspond to areas significant at the cluster level and orange shades to areas significant at the vertex level.

Figure 2.

Associations between CBCL Anxious/Depressed scores and cortical thickness centered from age 5 to 18 years old. The brain is shown in the right midsagittal view with the main association in the right ventromedial prefrontal cortex. Figure is shown at P ≤ 0.05 with a whole-brain random field theory correction. Note that a negative trend was present at age 9, and positive trends were present from age 15 to 17. Controlled for gender, total brain volume, and scanner.

Figure 3.

Scatterplot of the right ventromedial prefrontal cortex (vmPFC) mean cortical thickness against age in years (for visualization purpose). Values on the y-axis are the standardized residuals of the linear regression between right vmPFC and total brain volume, gender, and scanner to account for these variables. Subjects were divided in 2 groups based on Child Behavior Checklist Anxious/Depressed scores (A/D). Group 1 in black is composed of children with lower scores (A/D = 0 or 1), and group 2 in gray includes subjects with higher scores (A/D > 1).

Figure 4.

Brain areas where local cortical thickness is associated with YASR Anxious/Depressed raw score when controlling for gender, scanner, and total brain volume (n = 53 scans). Right midsagittal view on top and ventral view at the bottom. Brain areas not shown in this figure were not significant. Figure is shown at P ≤ 0.05 with a whole-brain random field theory correction. Blue shades correspond to areas significant at the cluster level and orange shades to areas significant at the vertex level.