Structural-functional correlations between hippocampal volume and cortico-limbic emotional responses in depressed children

Abstract

Although hippocampal atrophy and altered functional brain responses to emotional stimuli have been found in major depressive disorder (MDD), the relationship between the two is not yet well understood. The present study focused on children with and without a history of preschool onset MDD (PO-MDD) and directly examined the relations between hippocampal volume and functional brain activation to affect-eliciting stimuli. Children completed annual diagnostic assessments starting at preschool. When children were school-aged, high-resolution structural MRI and task-related functional MRI data were acquired from N = 64 nonmedicated children. During fMRI, subjects were shown emotional faces. Results from the total sample indicated that smaller bilateral hippocampal volumes were associated with greater cortico-limbic (e.g., amygdala, hippocampus, dorso-lateral prefrontal cortex) activation to sad or negative faces versus neutral faces. Left hippocampal volume was negatively associated with the cortico-limbic activation in both the PO-MDD and healthy children. Right hippocampal volume was negatively correlated with amygdala responses in the PO-MDD group, but not in the healthy comparison group. These findings suggest that there may be important interrelationships between reduced hippocampal volume and hyperactivation of brain responses in children, both those with and those without a history of PO-MDD.

Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals

“…The effect of BIN1 genotype on brain structure and FC can be interpreted by the hypothesis that the reduction in HF-DLPFC functional connectivity leads to a compensatory increase in hippocampal volume to maintain performance. One previous study also proposed a similar mechanism that hypersensitivity to negative stimuli in the DLPFC might lead to hippocampal atrophy by loss of or inhibited neurogenesis or synaptogenesis of neurons (Suzuki et al, 2013). Our finding of altered functional connectivity has been supported by cognitive neuroscience evidence indicating that the HF and the DLPFC form part of a distributed functional network of regions involved in AD (Allen et al, 2007;Wang et al, 2006) and memory (Preston and Eichenbaum, 2013) and that interactions between these regions are particularly important for WM (Axmacher et al, 2008;Ranganath, 2006).…”

Early Life Stress and Trauma and Enhanced Limbic Activation to Emotionally Valenced Faces in Depressed and Healthy Children

“…This hypothesis was based in part on the findings that PO-MDD is associated with neurobiological alterations in stress-responsive brain regions, including reduced hippocampal volume, 35 decreased functional connectivity between sgACC and cognitive control regions, 36 and greater functional activation to sad faces in the amygdala and hippocampus. 30, 31 …”

The neuroscience of depression: Implications for assessment and intervention

“…Although meta-analytic data in adults suggest that hippocampal volume reductions occur only after the onset of depression (McKinnon, Yucel, Nazarov, & MacQueen, 2009), studies of youth with MDD indicate that reductions in hippocampal volume are a consequence of depressive symptoms detected as early as the preschool years (Suzuki et al, 2013), and in young offspring of mothers with depression even before the onset of symptoms (Chen, Hamilton, & Gotlib, 2010). Across tasks assessing emotion processing, cognitive control, affective cognition, reward processing, and resting state, researchers have found elevated neural activity in the ACC, VMPFC and OFC, and amygdala in children and adolescents with MDD (Kerestes, Davey, Stephanou, Whittle, & Harrison, 2013).…”