Infant hippocampal volume is prospectively associated with irritability in toddlerhood

• In Event: Early signals of risk for psychopathology: Developmental approaches informed by the Research Domain Criteria

Abstract

Introduction: Irritability refers to the dispositional tendency toward angry emotion with both mood and behavioral elements. The dimensional spectrum of irritability is an RDoC-informed transdiagnostic marker of psychopathology risk, specifically the common and modifiable internalizing and externalizing (INT/EXT) disorders. Despite substantial interest in this most robust developmentally based transdiagnostic indicator of psychopathology risk, its early brain markers are understudied. Previous studies have identified the hippocampus and amygdala as regions of interest due to their role in emotion regulation and have found positive associations between irritability symptoms and gray matter volume in these regions in older youth. However, it is unclear if these relations are evident in the emergent phase of the clinical sequence in infancy (before frank INT/EXT disorder onset). Here, we present preliminary data, in which we examined associations between hippocampal/amygdala volumes at 12 months and the dimensional spectrum of irritability at 24 months old.
Hypotheses: We hypothesized that regions previously implicated in emotion regulation (the hippocampus and amygdala) would be prospectively associated with a developmentally based dimensional measure of irritability measured at 24 months.
Study Population: The analysis focused an imaging sample (n=42) that completed an MRI scan at 12 months and irritability measured at 24 months (mean age = 14.9 (1.4) months, 25 girls). The W2W sample consisted of a diverse sample of families recruited around infant’s first birthday from the greater Chicago area.
Methods: We examined whether infant hippocampal/amygdala volumes at 12 months were prospectively associated with toddler irritability. Hippocampal and amygdala segmentation was performed by the Infant Freesurfer pipeline (infantFS) using T1-weighted images and each were visual inspected for accuracy. One infant was removed due to poor image quality resulting in inaccurate subcortical segmentation. For irritability, we used the MAPS Temper Loss scale, the only scale specifically designed to characterize the normal-abnormal spectrum of irritability within developmental context. Four multiple regression analyses were conducted (left hippocampus, right hippocampus, left amygdala, right amygdala) to examine if hippocampal/amygdala volumes at 12 months old were prospectively associated with irritability at 24 months (using FDR correction). Each regression included infant sex, age at the time of scan, age at the time of assessment, income-to-needs ratio (as an SES indicator), and total intracranial volume as covariates.
Results: In multivariate analyses, left hippocampal volume at 12 months was associated with greater irritability at 24 months ( = 0.029, p = .048). Right hippocampal volume was at a trend level (p=.064), also in the positive direction, but did not survive multiple testing correction. Overall, we provide preliminary evidence that variations in infant left hippocampal volume are prospectively associated with toddler irritability. This finding is perhaps the first to demonstrate that patterns found in older youth of positive associations between hippocampal volume and irritability in children and adolescents are present as early as infancy. Future studies will replicate and extend these findings to examine joint consideration of hippocampal volume and irritability for predicting future INT/EXT symptoms and impairment.

Authors

• Alexander Dufford, Northwestern University
  Presenting Author

• Leigha Alexandra MacNeill, Northwestern University

• Ashley Nielsen

• Christopher D. Smyser, Washington University School of Medicine

• Elizabeth Norton, Northwestern University

• Lauren S Wakschlag, Northwestern University