Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions

Abstract

Background: Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample.

Methods: One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume.

Results: Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p < .001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions.

Conclusions: Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology.

Figure 1

Using whole-brain voxel-based morphometry, more cumulative adverse life events were associated with lower mean gray matter volume (GMV), after controlling for age, sex, and total intracranial volume in a region (20,679 voxels; familywise error p < .001) of the medial prefrontal cortex, anterior cingulate, and right insula (x = 5.4, y = 13.5, z = 11.5). R² for regression line = .17. ROI, region of interest identified in the whole-brain voxel-based morphometry.

Figure 2

Using whole-brain voxel-based morphometry, more frequent recent life events and more traumatic life events were associated with lower mean gray matter volume (GMV) after controlling for age, sex, and total intracranial volume. Regions of interest are displayed (top row: x = 43.5; y = 13.5, z = −6; bottom row: x = 4.0, y = 47.0, z = 3.0) with recent life events regions in red, traumatic life events regions in yellow, and overlapping regions indicated in orange. Recent life events are associated with a region of the medial prefrontal cortex (7131 voxels; familywise error [FWE] p = .001) and the right insula (3893 voxels; FWE p = .028). R² for the recent life events prefrontal region regression line = .13 and for the insula region = .13. Traumatic life events are associated with a region (12,835 voxels; FWE p <.001) of the medial prefrontal cortex, anterior cingulate, and subgenual areas. R² for the traumatic life events regression line = .15. ROI, region of interest identified in the whole-brain voxel-based morphometry.

Figure 3

Using whole-brain voxel-based morphometry, more cumulative adverse life events and greater chronic stress were associated with lower mean gray matter volume (familywise error p <.001; x = 4.5, y = 22.5, z = −12.5), after controlling for age, sex, and total intracranial volume and the main effects of both scales in a region (7175 voxels) of the orbitofrontal cortex, anterior cingulate, insula, and subgenual areas. The regression interaction is depicted in the graph.