Multimodal Neuroimaging of Suicidal Thoughts and Behaviors in a U.S. Population-Based Sample of School-Age Children

Abstract

Objective: Suicide deaths and suicidal thoughts and behaviors are considered a public health emergency, yet their underpinnings in the brain remain elusive. The authors examined the classification accuracy of individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates, of suicidal thoughts and behaviors in a U.S. population-based sample of school-age children.

Methods: Children ages 9-10 years (N=7,994) from a population-based sample from the Adolescent Brain Cognitive Development study were assessed for lifetime suicidal thoughts and behaviors. After quality control procedures, structural MRI (N=6,238), resting-state functional MRI (N=4,134), and task-based functional MRI (range, N=4,075-4,608) were examined. Differences with Welch's t test and equivalence tests, with observed effect sizes (Cohen's d) and their 90% confidence intervals <|0.15|, were examined. Classification accuracy was examined with area under precision-recall curves (AUPRCs).

Results: Among the 7,994 unrelated children (females, N=3,757, 47.0%), those with lifetime suicidal thoughts and behaviors based on child (N=684, 8.6%), caregiver (N=654, 8.2%), and concordant (N=198, 2.5%) reports had higher levels of social adversity and psychopathology, among themselves and their caregivers, compared with never-suicidal children (N=6,854, 85.7%). Only one imaging test survived statistical correction: caregiver-reported suicidal thoughts and behaviors were associated with a thinner left bank of the superior temporal sulcus. On the basis of the prespecified bounds of |0.15|, approximately 48% of the group mean differences for child-reported suicidal thoughts and behaviors comparisons and approximately 22% for caregiver-reported suicidal thoughts and behaviors comparisons were considered equivalent. All observed effect sizes were relatively small (d≤|0.30|), and both non-imaging and imaging correlates had low classification accuracy (AUPRC ≤0.10).

Conclusions: Commonly applied neuroimaging measures did not reveal a discrete brain signature related to suicidal thoughts and behaviors in youths. Improved approaches to the neurobiology of suicide are critically needed.

Keywords: Children; Neuroimaging; Risk Factors; Suicide.

Figure 1.. Percentage of outcomes of the Welch’s t-test and Equivalence test for each imaging modality by suicidal thoughts and behaviors group comparison.

For each informant, structural MRI examined 86 regions, resting-state fMRI examined 306 connectivity indices, and task-based fMRI examined activations in 167 regions. No evidence of difference (Welch’s t-test, p_FDR≥0.05,95% confidence interval (CI) includes zero), Evidence of difference (Welch’s t-test, p_FDR<0.05, 95%CI does not include zero). Evidence of equivalence (Equivalence test, p_FDR<0.05, 90%CI does not overlap with bounds); No evidence of equivalence (Equivalence test, p_FDR≥0.05, 90%CI overlaps with bound/s). sMRI, structural MRI. rs-fMRI, resting-state fMRI.

Figure 2.. Equivalence testing for mean differences in brain cortical thickness and subcortical volumes relating to suicidal thoughts and behaviors.

Distribution of t-values from Equivalence tests comparing the regional means between the never-suicidal group (n=5,381) and the child-reported suicidal thoughts and behaviors group (n=525) (Panel A) and the caregiver-reported suicidal thoughts and behaviors group (n=482) (Panel B); Higher t-values (i.e., darker green) suggest equivalence between groups. *Only the left bank of the temporal sulcus in the caregiver-reported suicidal thoughts and behaviors analysis showed to be statistically different and not statistically equivalent after FDR-correction.

Figure 3.. Equivalence testing for mean differences in functional activation during the Monetary Incentive Delay task, the Stop Signal Task and Emotional N-back task relating to suicidal thoughts and behaviors.

Distribution of absolute t-values from Equivalence tests comparing the regional means between the never-suicidal group and the child-reported suicidal thoughts and behaviors group (Panel A) and the caregiver-reported suicidal thoughts and behaviors group (Panel B); Higher t-values (i.e., darker green) suggest equivalence between groups. No statistical differences were found after applying FDR-correction for multiple comparisons. The remaining contrasts are depicted in Supplementary eFigure 60.

Figure 4.. Observed effect sizes of mean differences for each imaging modality by suicidal thoughts and behaviors group comparison.

For each informant, structural MRI examined 86 regions, resting-state fMRI examined 306 connectivity indices, and task-based fMRI examined activations in 167 regions. Blue individual lines represent effect size of group mean differences for a region or connectivity index. Shaded area represents effect size lower than the prespecified smallest effect size of interest (SESOI) of d=|0.15|. sMRI, structural MRI. rs-fMRI, resting-state fMRI.