Ventromedial prefrontal cortex thinning in preschool-onset depression

Abstract

Background The ventromedial prefrontal cortex (VMPFC) is a key center of affect regulation and processing, fundamental aspects of emotional competence which are disrupted in mood disorders. Structural alterations of VMPFC have consistently been observed in adult major depression and are associated with depression severity, yet it is unknown whether young children with depression demonstrate similar abnormalities. We investigated cortical thickness differences in the VMPFC of children with a history of preschool-onset depression (PO-MDD). Methods Participants in a longitudinal study of PO-MDD underwent structural brain imaging between the ages of 7 and 12 years. Using local cortical distance metrics, cortical thickness of the VMPFC was compared in children with and without a history of PO-MDD. Results Children previously diagnosed with PO-MDD (n=34) had significantly thinner right VMPFC vs. children without a history of PO-MDD [(n=95); F(1,126)=5.97, (p=.016)]. This effect was specific to children with a history of PO-MDD vs. other psychiatric conditions and was independent of comorbid anxiety or externalizing disorders. Decreases in right VMPFC thickness were predicted by preschool depressive symptoms independent of depressive symptoms in school age. Limitations Results are cross-sectional and cannot distinguish whether thinner right VMPFC represents a vulnerability marker of MDD, consequence of MDD, or marker of remitted MDD. Longitudinal imaging is needed to contextualize how this difference relates to normative VMPFC structural development. Conclusions Onset of depression at preschool age was associated with decreased cortical thickness of right VMPFC. This finding implicates the VMPFC in depression from very early stages of brain development.