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Lifespan Changes of the Human Insula in Major Depression

Abstract

Using cross-sectional structural magnetic resonance imaging (MRI) data from six cohorts originating from three sites, this study investigated the cortical morphometric trajectories of six insular subregions of individuals with major depressive disorder (MDD) compared to healthy individuals across the lifespan to better understand the neurodevelopmental and neurodegeneration aspects of MDD. The insula is a centrally located region of the brain responsible for emotional regulation and awareness and has been implicated in many psychiatric disorders including MDD. Participants across all sites included in this study totaled 203 individuals with current MDD (F=137, M=66) and 215 healthy controls (F=110, M=105). T1-weighted magnetic resonance (MR) images from each cohort were registered and segmented using Advanced Normalization Tools (ANTs) and a 3D probabilistic atlas of the human brain, including the following insular regions: posterior long gyrus, anterior long gyrus, anterior short gyrus, middle short gyrus, posterior short gyrus, and anterior inferior cortex. In addition, we examined the amygdala, anterior cingulate gyrus, lateral occipital cortex, cuneus, subgenual cortex, and lateral orbitofrontal cortex. The outputs were then standardized and harmonized to adjust site effects in morphometric measurements while preserving biological variation due to age, sex, relative intracranial volume, and diagnosis. We hypothesized that the relationships among morphometric measures and age are dynamic across the lifespan and influenced by MDD. For each region of interest considered in this study, linear, quadratic, and cubic models were tested to model morphometry and age association first within each group separately and then tested for group-age interaction. Our statistical analyses indicate that the volumes of all insular subregions in the left hemisphere, as well as the right anterior short gyrus, middle short gyrus and anterior long gyrus, exhibited a significant age-associated difference between the control and MDD groups. Furthermore, the group-age interaction revealed that these deviations were particularly significant for 60-79 years of age, indicating co-morbidity of depression with neurodegeneration. Most non-insular regions showed significant differences between groups, but association with age was less robust. Results for the surface area analysis were less conclusive. Further analysis of other metrics related to neurodevelopment (i.e. cortical thickness) will better inform this facet of the disease.

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