Summary Objective Using a hypothesis driven approach, subcortical and cortical regions implicated in anxiety disorders in the general population were examined in children with recent-onset epilepsy with versus without anxiety compared to controls. This study reports frequency of anxiety disorders while examining familial, clinical and demographic variables associated with anxiety in children with epilepsy. Method Participants included 88 children with epilepsy aged 8–18 years; 25 with a current anxiety disorder and 63 children with epilepsy no current anxiety disorder. 49 controls without anxiety disorders were included. T1 volumetric MRI scans were collected; subcortical volumes and cortical thickness were computed using the FreeSurfer image analysis suite. Analyses focused on adjusted measures of subcortical volumes and cortical thickness. Results Relative to controls, larger left amygdala volumes were found in the Epilepsy Anxiety group compared to the Epilepsy No Anxiety group (p = 0.027). In the hippocampus there were no significant differences between groups. Examination of cortical thickness demonstrated that the Epilepsy Anxiety group showed thinning in left medial orbitofrontal (p=0.001), right lateral orbitofrontal (p=0.017), and right frontal pole (p=0.009). There were no differences between groups in age, sex, IQ, age of onset, medications, or duration of epilepsy. There were more family members with a history of anxiety disorders in the Epilepsy Anxiety group compared to the Epilepsy No Anxiety group (p=0.005). Significance Anxiety is a common psychiatric comorbidity in children with recent-onset epilepsy with volumetric enlargement of the amygdala and thinner cortex in orbital and other regions of prefrontal cortex, suggesting structural abnormalities in brain regions that are part of the dysfunctional networks reported in individuals with anxiety disorders in the general population. These findings are evident early in the course of epilepsy, are not related to chronicity of seizures, and may be linked to a family history of anxiety and depressive disorders.

Summary Objective Birth weight is an important indicator of prenatal environment and subtle variations of birth weight within the normal range have been associated with differential risk for cognitive and behavioral problems. Therefore, we aimed to determine if there are differences in birth weight between full term children with uncomplicated new/recent-onset epilepsies and typically-developing healthy controls. We further examined the relationships between birth weight and childhood/adolescent cognition, behavior, and academic achievement. Methods 108 children with new/recent-onset epilepsy and 70 healthy controls underwent neuropsychological assessment. All participants were born full-term (>37 weeks) without birth complications. Parents were interviewed regarding their child's gestation, birth and neurodevelopmental history. Results Birth weight of children with epilepsy was significantly lower than healthy controls (p=0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's education) was significantly associated with cognition in controls in multiple domains (intelligence, language, aspects of academic achievement), this relationship was absent in children with epilepsy. Birth weight was not associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and was not predictive of a variety of other academic or psychiatric comorbidities of epilepsy. Significance Although the origin of lower birth weight in children with epilepsy is unknown, these findings raise the possibility that abnormal prenatal environment may impact childhood-onset epilepsy. Furthermore, the positive relationship between birth weight and cognition evident in healthy controls was disrupted in children with epilepsy. However, birth weight was not related to academic and psychiatric comorbidities of childhood epilepsy.