Amygdala Functional Connectivity During Self-Face Processing in Depressed Adolescents With Recent Suicide Attempt

Objective: Suicide is the second leading cause of death among adolescents; however, objective biomarkers of suicide risk are lacking. Aberrant self-face amygdala activity is associated with suicide ideation, and its connectivity with neural regions that enable self-processing (eg medial prefrontal cortex) may be a suicide risk factor. Method: Adolescents (aged 11-17 years; N = 120) were sorted into four groups: healthy controls (HC), depressed individuals with low suicide ideation (LS), depressed individuals with high suicide ideation (HS), and depressed suicide attempters (SA). Youth completed an emotional (Happy, Sad, Neutral) self-face recognition task in the scanner. Bilateral amygdala task-dependent functional connectivity was determined with psychophysiological interaction analysis. Connectivity was compared across groups and within Self versus Other faces across emotions and hemispheres. Voxelwise results were thresholded (p < .005, uncorrected) and corrected for multiple comparisons (p < .05, familywise error). Results: Both HS and SA displayed greater amygdala connectivity with the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and pre-cuneus, compared to LS, who, in turn, showed greater connectivity than HC. Greater left amygdala-rostral anterior cingulate cortex (rACC) connectivity was observed in SA compared to all other groups, whereas right amygdala-rACC connectivity was greater in HS versus LS and HC. Conclusion: Greater connectivity between amygdala and other regions implicated in self-face processing differentiated suicide ideation and suicide attempt groups. A dose-dependent response showed that greater rACC-left amygdala connectivity during self-face processing was associated with a recent suicide attempt, but that a greater rACC-right amygdala connectivity was associated with suicide ideation.