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

Abstract Suicidal ideation and attempt might have distinct neural underpinnings. Identifying the neural substrates of suicide behaviors might help to reduce suicide rates. This study wanted to identify i) neural markers of suicide attempt using resting-state functional magnetic resonance imaging (rs-fMRI), and ii) associations between rs-fMRI metrics, suicidal phenotype and peripheral blood inflammation markers. We measured inflammation markers [C-reactive protein (CRP), interleukin (IL)-1b, IL-2, IL-6, TNF-a) and rs-fMRI metrics in 20 healthy controls (HCs) and 42 patients with unipolar depression [n=21 suicide attempters (SAs) in the last 8 days and n=21 affective controls (ACs) without lifetime history of suicide]. Amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and Voxel-Mirrored Homotopic Connectivity (VMHC) were estimated in prefrontal cortex, anterior cingulate cortex and insula. Participants were mainly women (66.7% of HCs, 71.4% of ACs and 85% of SAs; age range 40 to 48 years). CRP (but not IL) concentration was higher in SAs than ACs and HCs. ALFF values were decreased in the pars opercularis of the inferior frontal gyrus in SAs vs. ACs and HCs, even after controlling for suicidal ideation intensity and CRP level. Suicidal ideation intensity was negatively correlated with all rs-fMRI metrics (except ReHo of left side) of this region in SAs and ACs. Inflammation markers were not correlated with the rs-fMRI metrics. Resting-state dysfunctional connectivity in regions involved in language and cognitive control is associated with suicide intensity and attempts, but not with inflammation markers.