Structural MRI correlates for vulnerability and resilience to major depressive disorder

Abstract

15Background: In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD. Methods: We compared healthy controls with a positive family history for MDD (HC-FHP), healthy controls with no family history of any psychiatric disease (HC-FHN) and patients with MDD. Groups were age-and sex-matched. We analyzed data from high-resolution magnetic resonance imaging using voxel-based morphometry. We performed small volume corrections for our regions of interest (hippocampus, dorsolateral [DLPFC] and dorsomedial prefrontal cortex [DMPFC], anterior cingulate cortex [ACC] and basal ganglia) using a family-wise error correction (p < 0.05) to control for multiple comparisons. Results: There were 30 participants in the HC-FHP group, 64 in the HC-FHN group and 33 patients with MDD. The HC-FHP group had smaller right hippocampal and DLPFC grey matter volumes compared with the HC-FHN group, and even smaller right hippocampal volumes compared with patients with MDD. In addition, the HC-FHP group exhibited smaller white matter volumes in the DLPFC and left putamen but also greater volumes in 2 areas of the DMPFC compared with the HC-FHN group. Patients with MDD exhibited smaller volumes in the ACC, DMPFC, DLPFC and the basal ganglia compared with healthy controls. Limitations: The retrospective identification of family history might result in a bias toward unidentified participants in the control group at risk for MDD, diminishing the effect size. Conclusion: Volume reductions in the hippocampus and DLPFC might be associated with a greater risk for MDD. The HC-FHP group had smaller hippocampal volumes compared with patients with MDD, which is suggestive for neuroplastic effects of treatment. The HC-FHP group had not yet experienced a depressive episode and therefore might have been resilient and might have had some protective strategies. Whether resilience is associated with the larger white matter volumes in the DMPFC (e.g., owing to compensatory, neuroplastic remodelling mechanisms) needs to be confirmed in future studies.

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

“…This discovery is in agreement with previous findings about the importance of a family history of depression in diagnosis [1][2][3][4]43 and neuroimaging 6,8,9 of individuals with MDD. As predicted, neural mechanisms of emotion processing and attention shifting from the said processing are affected by the aforementioned modulation.…”

“…Some of the areas of the attention control network have been previously reported as having smaller volumes in the HC-FHP group. 6 That may put an additional strain on the attention network.…”

“…These individuals were discovered to have reduced volume of the right hippocampus, the dorsolateral prefrontal cortex and the putamen. 6,7 When a small volume correction was applied in a functional magnetic resonance imaging (fMRI) experiment, healthy adolescents with a family history of MDD displayed altered activation in the amygdala and nucleus accumbens when observing emotional faces. 8 Also, healthy monozygotic twins of patients with MDD showed greater activation in the left infer ior frontal gyrus during verbal encoding and retrieval.…”

The Effects of Psychotherapy on Brain Function — Major Depressive Disorder

“…[13,14] This result explains some of the hereditary aspects of depression, thereby indicating the association of the neuroimaging findings with the risk factors on depression. [15,16] In a study on functional neuroimaging, there is a remarkable mood-down-regulation effect due to the increased task in the normal group with a family history of depression than in the normal group without a family history of depression. Furthermore, the activation of the amygdala significantly increased in the normal group with a family history of depression as compared to the other group.…”

Hippocampal Atrophy in Major Depression: a Function of Childhood Maltreatment Rather than Diagnosis?

“…Alterations in this structure have been found to be associated with various clinical and demographic characteristics in patient samples (McKinnon et al, 2009). However, some studies indicate that reduced hippocampal volumes might be apparent before onset of disease in subjects at risk for depression (Amico et al, 2011). Hence, hippocampal alterations have been suspected to mediate the effect of longterm stressful life events on depression risk rather than constituting a disease marker (Frodl et al, 2010b).…”