Letter to the Editor: New neural perspective on suicidal behavior in adolescent depression: Specific amygdala subregional dysconnectivity with visual and socio-cognitive networks

Abstract

This letter discusses a recent case-control study by Cheng et al, which investigated alterations in resting-state functional connectivity (rsFC) in adolescents with major depressive disorder (MDD) and a history of suicide attempt (sMDD), with a specific focus on the subregions of the amygdala and their connectivity with whole-brain networks. The study included 32 sMDD patients, 33 MDD patients without suicide attempt (nsMDD), and 34 healthy controls, using resting-state functional magnetic resonance imaging. The results revealed that, compared with the nsMDD group, the sMDD group exhibited significantly reduced rsFC between the right lateral amygdala and both the right inferior occipital gyrus and the left middle occipital gyrus. Furthermore, within the sMDD group, rsFC between the right medial amygdala and the right superior temporal gyrus was negatively correlated with self-esteem scores, while rsFC between the left lateral amygdala and the right parahippocampal gyrus was positively correlated with interpersonal stress scores. These findings underscore abnormal functional connectivity between amygdala subregions and brain areas involved in visual processing, emotion, and social cognition, which may represent a potential neural mechanism underlying suicidal behavior in depressed adolescents. Future studies should integrate multimodal neuroimaging and longitudinal designs to validate these findings and provide a neurobiological basis for early identification and intervention of suicide risk in adolescent depression.

Keywords: Major depressive disorder; Adolescent; Suicide attempt; Amygdala; Functional connectivity

Core Tip: Adolescents with major depressive disorder and a history of suicide attempts exhibit reduced resting-state functional connectivity between the right lateral amygdala and visual association areas (bilateral occipital lobes), along with abnormal connections involving the parahippocampal gyrus and superior temporal gyrus. These neural patterns are further correlated with lower self-esteem and higher interpersonal stress, offering an integrated neurobiological model linking emotional regulation, self-evaluation, and environmental stress in adolescent suicidality. The findings highlight the potential of amygdala subregion-based analysis in identifying specific neural circuits associated with suicide risk, paving the way for future biomarker development and targeted interventions.