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 to 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 versus children without a history of PO-MDD [(n=95); F(1,126)=5.97, p=0.016)]. 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.

Anxiety, depression, impulsivity, and brain structure in children and adolescents

“…In adults, major depressive disorder (MDD) tends to be linked with decreased CT in PFC regions, although areas of thickening have been found ( Lener et al, 2016 ; Peterson et al, 2009 ; Schmaal et al, 2016 ; Tu et al, 2012 ; van Eijndhoven et al, 2013 ). Similarly, some studies of pediatric MDD have indicated decreased CT in PFC regions ( Marrus et al, 2015 ; Peterson et al, 2009 ) (see Supplementary Table S2). In addition, in a longitudinal neuroimaging study, greater depressive symptoms or an MDD diagnosis at 3–6 years of age was associated with an increased rate of global cortical thinning across middle childhood and into early adolescence ( Luby et al, 2016 ).…”

The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex

“…Dysfunction caused by dlPFC damage in stroke is considered a predisposing factor to poststroke depression [ 56 ]. In addition, a decrease of cortical thickness in the right vmPFC, which occurs in the early stages of neurodevelopment, results in depression in preschoolers [ 57 ]. Volume reduction of the prefrontal cortex may result from the disruption and atrophy of neurons and glia in depression, as observed in the hippocampus [ 21 , 22 ].…”

Depression and Anxiety in Preschoolers

“…There have been several studies that investigated neural correlates of currently depressed preschoolers 71,72 and in children/adolescents with a history of preschool depression 52,73–81 . For example, one study used functional magnetic resonance imaging (fMRI) to examine functional brain activity and its relationship to emotion regulation in n=23 currently depressed, 4–6 year old preschoolers and n=31 matched, healthy preschoolers 71 .…”