Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective

Abstract

The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research.

Figure 1

Representation of the four regions-of-interest of the prefrontal cortex examined in this article. Blue: medial prefrontal cortex (MPFC; including anterior cingulate cortex, not shown); red: dorsal prefrontal cortex (DPFC); green: orbitofrontal cortex (OFC); violet: ventrolateral prefrontal cortex (VLPFC). VBM, voxel-based morphometry.

Figure 2

Effect sizes between suicide attempters and both control groups for the four regions-of-interest. DPFC, dorsal prefrontal cortex; MPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; VBM, voxel-based morphometry; VLPFC, ventrolateral prefrontal cortex. Blue: suicide attempters vs patient controls; black: suicide attempters vs healthy controls.

Figure 3

Correlation map between all magnetic resonance imaging measures for the four regions-of-interest. DPFC, dorsal prefrontal cortex; L, left; MPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; R, right; VBM, voxel-based morphometry; VLPFC, ventrolateral prefrontal cortex.