AbstractThe transition from suicidal ideas to a suicide act is an important topic of research for the identification of those patients at risk of acting out. We investigated here whether specific brain activity and connectivity measures at rest may be differently associated with suicidal thoughts and behaviors. A large sample of acutely depressed patients with major depressive disorder was recruited in three different centers (Montreal/Canada, Stanford/USA, and Jena/Germany), covering four different phenotypes: patients with a past history of suicide attempt (n = 53), patients with current suicidal ideas but no past history of suicide attempt (n = 40), patients without current suicidal ideation nor past suicide attempts (n = 42), and healthy comparison subjects (n = 107). 3-T resting-state functional magnetic resonance imaging (fMRI) measures of the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were obtained and examined in a whole-brain data-driven analysis. Past suicide attempt was associated with a double cortico-subcortical dissociation in ALFF values. Decreased ALFF and DC values mainly in a frontoparietal network and increased ALFF values in some subcortical regions (hippocampus and thalamus) distinguished suicide attempters from suicide ideators, patient controls, and healthy controls. No clear neural differences were identified in relation to suicidal ideas. Suicide attempters appear to be a distinct subgroup of patients with widespread brain alterations in functional activity and connectivity that could represent factors of vulnerability. Our results also indirectly support at the neurobiological level the relevance of the transition model described at the psychological and clinical levels. The brain bases of suicidal ideas occurrence in depressed individuals needs further investigations.