Abstracts

Rationale: The structural and functional importance of the amygdala (AMYG) and prefrontal cortex (PFC) has been described in individuals with anxiety, but this subcortical-cortical circuitry has not been examined in children with epilepsy (CWE) plus comorbid anxiety. We investigated AMYG volume and PFC thickness in children with new/recent-onset epilepsy plus anxiety compared to those with epilepsy only, relative to controls.Methods: Participants were CWE (ages 8-18) and current anxiety (n=24), epilepsy only (n=64), and non-anxious controls (n=50). All CWE were assessed within 12 months of epilepsy diagnosis, had normal neurological examinations, and no lesions on clinical MRI. Controls were age- and gender-matched first-degree cousins. All participants completed a semi-structured psychiatric interview and had T1 volumetric MRI scans. Grey and white matter volumes were computed using the FreeSurfer image analysis suite. Analyses included AMYG volume and PFC thickness in several FreeSurfer-defined frontal regions of interest (ROI s). All measures were corrected for age and sex effects; volumetric analyses were also corrected for intracranial volume. To limit family-wise error due to multiple comparisons, difference scores were computed by subtracting epilepsy participant volume and thickness measures from the mean respective control values, which allowed direct comparison of CWE with (Epi + Anx) and without (Epi Anx) anxiety, relative to controls. Finally, correlations between AMYG volume and PFC thickness were examined within each group.Results: Significance for each comparison was assessed at p 0.05. Epi + Anx children had significantly larger left AMYG volumes than Epi Anx children. Epi + Anx children also had significantly thinner cortex than Epi Anx children in left medial orbital, right lateral orbital, and right frontal pole ROI s. In the Epi + Anx group, left AMYG volume was positively correlated with ipsilateral cortical thickness in superior frontal (r = 0.55), rostral middle frontal (r = 0.49), and inferior frontal (pars orbitalis, r = 0.46) gyri. Conversely, in the Epi Anx group, negative correlations were found between left AMYG volume and ipsilateral caudal middle frontal gyral thickness (r = 0.25), and right AMYG volume and right inferior frontal gyral (pars operularis) thickness (r = -0.34). Controls had no significant left- or right-sided correlations.Conclusions: CWE plus comorbid anxiety showed abnormalities in AMYG volume and frontal cortical thickness near the onset of epilepsy. Furthermore, anxious CWE showed positive correlations between left AMYG volume and cortical thickness at multiple ipsilateral frontal ROI s. In contrast, non-anxious CWE showed negative correlations between left/right AMYG volume and ipsilateral frontal ROI s--a pattern consistent with current theories of top-down regulation of AMYG function as cortical maturation occurs. We hypothesize that structural PFC and AMYG abnormalities represent a neuroanatomical substrate for clinically significant anxiety disorders in CWE.