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

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.

Keywords: Adolescents; Brain Imaging Techniques; DTI; MRI; Mood Disorders-Bipolar; Suicide; fMRI.

Figure 1. Decreased Gray Matter Volume in Individuals With Bipolar Disorder With, Compared to Without, Suicide Attempts^a

^a The structural magnetic resonance T1 axial-oblique and sagittal images display right orbitofrontal cortex, right hippocampal and cerebellum regions where gray matter volume was decreased in the group with bipolar disorder with suicide attempts, compared to the group without suicide attempts (p<0.005, meeting AlphaSim spatial extent threshold for p<0.05, corrected). The numbers are the Montreal Neurological Institute coordinates (mm) for the corresponding plane. The color bar represents the range of T-values. The right side of the axial-oblique images is on the right side of the brain.

Figure 2. Decreased Fractional Anisotropy in Individuals With Bipolar Disorder With, Compared to Without, Suicide Attempts^a

^a Axial-oblique images display areas of decreased fractional anisotropy, in regions of the bilateral uncinate fasciculus, extending on the left into left ventral frontal cortex, and cerebellum in the group with bipolar disorder with suicide attempts, compared to the group without suicide attempts (p<0.005, meeting AlphaSim spatial extent threshold for p<0.05, corrected). The numbers are the Montreal Neurological Institute coordinates (mm) for the z-plane. The left uncinate was negatively associated with suicide ideation severity (p<0.05). The color bar represents the range of T-values. The right side of the axial-oblique images is on the right side of the brain.

Figure 3. Decreased Functional Connectivity in Individuals With Bipolar Disorder With, Compared to Without, Suicide Attempts^a

^a Axial-oblique images display the regions of decreased functional connectivity from the amygdala, in the group with bipolar disorder with suicide attempts, compared to the group without suicide attempts, to left ventral prefrontal cortex during happy (top row, p<0.0016, meeting AlphaSim spatial extent threshold for p<0.05, corrected), neutral (middle row, p<0.0016, meeting AlphaSim spatial extent threshold for p<0.05, corrected), and fearful face (bottom row, p<0.0016, uncorrected) conditions and to right rostral prefrontal cortex in the neutral face (second row, right two images, p<0.0016, meeting AlphaSim spatial extent threshold for p<0.05, corrected) condition. The numbers are the Montreal Neurological Institute coordinates (mm) for the z-plane. Functional connectivity in all areas was negatively associated with suicide ideation severity (p<0.05). Only the region of reduced amygdala-ventral prefrontal connectivity was negatively associated with lethality of most severe attempt in all three face conditions (p<0.05). The color bar represents the range of T-values. The right side of the axial-oblique images is on the right side of the brain.