Multimodal Neuroimaging of Frontolimbic Structure and Function Associated With Suicide Attempts in Adolescents and Young Adults With Bipolar Disorder

TLDR

Bipolar disorder carries a high risk of suicidal behavior, especially during adolescence and young adulthood. The study aims to identify neural systems involved in suicidal behavior to aid prevention. The authors compared structural, diffusion tensor, and functional MRI data from 26 bipolar adolescents/young adults who had attempted suicide with 42 who had not, assessing gray‑matter volume, white‑matter integrity, and amygdala‑prefrontal connectivity during emotional processing. Suicide attempters showed reduced gray‑matter volume in orbitofrontal cortex, hippocampus, and cerebellum, diminished white‑matter integrity in the uncinate fasciculus and related regions, and weaker amygdala‑prefrontal connectivity, with lower connectivity linked to greater suicidal ideation and attempt lethality.

Abstract

Objective: Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems. Method: The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Results: Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality. Conclusions: Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala–prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.