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.

The role of cytokines in the pathophysiology of suicidal behavior

“…Decreased brain volumes in the prefrontal cortex of suicidal patients also have been described (Ding et al, 2015), possibly reflecting neuroplasticity impairment. Pro-inflammatory cytokines are associated with decreased neurogenesis and induce reductions in BDNF expression, mRNA and protein levels (Calabrese et al, 2014).…”

Reduced left precentral regional responses in patients with major depressive disorder and history of suicide attempts

“…A magnetic resonance imaging (MRI) study found that depressed patients at high suicide risk had a significantly thinner cortex in the left dorsolateral and ventrolateral prefrontal regions than those at a lower suicide risk [7]. A recent MRI study indicated that suicide attempters (SAs) with a past history of mood disorders have reduced activity in the left ventrolateral prefrontal cortices compared with healthy controls (HCs) and with patient controls with a past history of mood disorders but not of suicidal behavior [8]. Furthermore, functional MRI (fMRI) studies have shown that SAs can be distinguished from non-attempters (NAs) by specific frontal cortex activation patterns in response to angry and happy versus neutral faces [9] and by decreased activation in the medial prefrontal cortex while reading autobiographical accounts of recent suicide attempts compared with while reading neutral scripts [10].…”

Understanding epigenetic architecture of suicide neurobiology: A critical perspective

“…The brain’s inability to respond properly to environmental stimuli due to impaired structural and neural plasticity has been well-established to cause suicide pathogenicity (Dwivedi, 2009, 2010; Furczyk et al, 2013). Recent neuroimaging identification of orbitofrontal and dorsolateral prefrontal cortex based structural abnormalities in suicide victims further reinforces the importance of impaired neuronal plasticity (Ding et al, 2015; van Heeringen et al, 2011). An overwhelming concern and ever-increasing need to better apprehend this compromised structural and functional plasticity, eventually unfolded the role of brain-derived neurotrophic factor (BDNF) and its cognate receptor molecule tropomycin receptor kinase B (TRKB) in suicide neurobiology (Dwivedi, 2009, 2010; Dwivedi et al, 2003; Lee and Kim, 2010; Pandey et al, 2008).…”