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.
Highlights
Magnetic resonance imaging (MRI) studies of subjects with major depressive disorder (MDD), or at risk for developing MDD, have greatly improved our understanding of the neurocircuitry involved in internalizing disorders (Peterson et al 2009; Chen et al 2010; Price and Drevets 2012)
This study revealed a strong interaction between age and Child Behavior Checklist (CBCL) Anxious/Depressed syndrome (A/D) scores on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbitofrontal cortex (OFC), gyrus rectus, and subgenual anterior cingulate cortex (SgACC)
The right vmPFC was the only cortical area in which thickness was significantly associated with the “A/D by age” interaction
Summary
Magnetic resonance imaging (MRI) studies of subjects with major depressive disorder (MDD), or at risk for developing MDD, have greatly improved our understanding of the neurocircuitry involved in internalizing disorders (Peterson et al 2009; Chen et al 2010; Price and Drevets 2012). At the level of the cerebral cortex, medial prefrontal cortices (mPFC), in particular the ventromedial prefrontal cortex (vmPFC), have been most consistently associated with major depression, normal sadness, and negative affect, both in morphometric and functional imaging studies (Drevets et al 1997; Rajkowska et al 1999; Drevets 2000, 2007; Zald et al 2002; Coryell et al 2005; Drevets, Savitz, et al 2008; van Tol et al 2010; Hamani et al 2011; Myers-Schulz and Koenigs 2012) This area of the prefrontal cortex includes the anterior cingulate cortex (ACC), the subgenual anterior cingulate cortex (SgACC), and the medial orbitofrontal cortex (OFC) (Bremner et al 2002; Drevets 2007; Drevets, Price et al 2008; Hamani et al 2011). Few studies have looked at neuroanatomical correlates of pediatric depressive and anxious symptoms in nonclinical populations. Boes et al (2008) found that rostral ACC volume in healthy boys of 7–17 years of age was negatively correlated with depressive symptoms
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