Age-related volumetric change of limbic structures and subclinical anxious/depressed symptomatology in typically developing children and adolescents

Abstract

Objective: To investigate the extent to which subclinical variation in anxious/depressed psychopathology is associated with volume and age-related volumetric change of limbic structures in a longitudinal sample of healthy youths.

Methods: Linear mixed-effects models were used to analyze longitudinal behavioral and neuroimaging data (up to 3 data points per subject, collected at 2 year-intervals) in 371 typically developing youths, from 4 to 18 years of age (196 females; 723 MRIs). Volumetric measures were obtained using a validated segmentation method. The best-fit model (cubic, quadratic, or first-order linear) was determined for the effect of age on amygdalar and hippocampal volume (adjusted for total brain volume). Next, amygdalar and hippocampal volumes were regressed against Child Behavior Checklist Anxious/Depressed (A/D) scores. Age-by-A/D and sex-by-A/D interactions were tested.

Results: Analyses revealed age-related linear and quadratic volumetric change in the amygdalae and hippocampi, respectively. A/D was positively associated with total amygdalar volume (p=0.045), independent of age and sex. Age-by-A/D and sex-by-A/D interactions were not associated with amygdalar or hippocampal volume.

Conclusions: Results suggest that amygdalar structure is tied to A/D among typically developing youths, independent of age and sex. Developmental trajectories of amygdalar and hippocampal volume were not associated with subclinical anxiety. Taken together, increased amygdalar volume may serve as a significant marker of anxiety, regardless of developmental phase.

Keywords: Amygdala; Anxiety; Development; Hippocampus.