Association of Suicidal Status, Inflammation Markers, and Resting-State Functional Activity and Connectivity in Patients With Major Depressive Disorder

Abstract. Background: This study aimed to identify (1) neural markers of suicide attempt using resting-state functional magnetic resonance imaging (rs-fMRI) and (2) associations between rs-fMRI metrics and resting-state functional connectivity (rs-FC), suicidal phenotype, and peripheral blood inflammation markers. Methods: Inflammation markers (C-reactive protein CRP, interleukin IL-1β, IL-2, and IL-6, and tumor necrosis factor-α TNF-α) and rs-fMRI metrics were measured in 20 healthy controls (HCs) and 42 patients with unipolar depression according to the DSM-5 criteria (n = 21 suicide attempters SAs in the last 8 days and n = 21 affective controls ACs without lifetime suicidal history) between February 1 and November 30, 2017. Amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity, and rs-FC were estimated in prefrontal cortex, anterior cingulate cortex, and insula. Results: Participants were mainly women (age: 40-48 years). Only CRP concentration was higher in SAs than in ACs and HCs (3.55 0.5; 13.3 vs 0.6 0.3; 4.4 vs 0.8 0.3; 13.9 mg/L, respectively, P < 10-3). ALFF values in the pars opercularis of the inferior frontal gyrus (IFG) were lower in SAs than in ACs and HCs (all P < 10-2), even after controlling for suicidal ideation intensity and CRP level. Suicidal ideation was negatively correlated with all rs-fMRI metrics (except ReHo of left side) of this region in patients. The rs-FC values of bilateral anterior cingulate cortex, left orbital IFG, and middle frontal orbital gyrus were higher in SAs than in ACs and HCs (all P < .05). Conclusions: Resting-state activity and connectivity in regions involved in language, cognitive control, and decision making may be associated with suicidal behaviors, but not with inflammation markers. Trial Registration: ClinicalTrials.gov identifier: NCT03052855.