ABSTRACT
Introduction: Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt. Methods: We examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (MAge [SD] = 16.4[0.3], 41% male) and 13 with AT (MAge [SD] = 16.2[0.3], 31% male). Results: Only the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise p<.001, cluster-wise p<.01). No significant associations were found between any putamen RSFC patterns and suicidal ideation severity or lethality of attempts among those who had attempted. Discussion: The results align with recent adult literature and have interesting theoretical and clinical implications. A possible interpretation of the results is a mismatch of the serotonin transport to putamen and to the supplementary motor area and the resulting reduced functional connectivity between the two areas in adolescents with attempt history. The obtained results can be used to enhance the diathesis-stress model and the Emotional paiN and social Disconnect (END) model of adolescent suicidality by adding the putamen. We also speculate that connectivity between putamen and the supplementary motor area may in the future be used as a valuable biomarker of treatment efficacy and possibly prediction of treatment outcome.
ABSTRACT
Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9-10 predicts increased odds of alcohol sipping at ages 11-13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11-13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11-13 (p < .05). TBI and left frontal pole activity interacted to predict alcohol sipping (OR = 0.507, 95% CI [0.303 - 0.846], p = .009) - increased activity predicted decreased odds of alcohol sipping for those with a TBI (OR = 0.516, 95% CI [0.314 - 0.850], p = .009), but not for those without (OR = 0.971, 95% CI [0.931 -1.012], p = .159). These findings suggest that for youth with a TBI, increased BOLD activity in the frontal pole, underlying working memory, may be uniquely protective against the early initiation of alcohol experimentation. Future work will examine TBI and alcohol misuse in the ABCD cohort across more time points and the impact of personality traits such as impulsivity on these associations.