A Transdiagnostic Study of Emotional Impulsivity in Suicidal Ideation and Behavior

PROJECT SUMMARY/ABSTRACT Suicidal ideation and behavior (SIB) is an important public health problem. This is particularly true in two serious mental health disorders, schizophrenia spectrum disorder (SSD) and major depressive disorder (MDD), in whom 5% and 1.9% die by suicide over their lifetimes, a rate 100 times higher than in the general

population. An understanding of the mechanisms underlying SIB is therefore critical to address this issue. Recently, we found that a questionnaire-based measure (the UPPS-P) of emotionally based impulsivity (urgency) is highly elevated with suicide risk in SSD (d = 1.13) and was correlated with suicidal ideation and

lifetime suicide attempts. We also found that high levels of SIB in SSD were associated with reduced activation in putative urgency circuitry during an urgency proxy fMRI task. These regions included right dorsolateral prefrontal cortex, right medial prefrontal cortex, right rostral anterior cingulate, right superior temporal gyrus,

and right middle cingulate. Activation in most of these regions correlated with lower levels of urgency. Prior work in SSD also implicates the frontal pole and left lateral orbitofrontal cortex dysfunction in higher levels of urgency. We propose a transdiagnostic study to examine the role of urgency and its neural circuitry in

these high-risk populations. We plan to leverage prior collaborations among NYU Grossman School of Medicine, Nathan Kline Institute, and Weill Cornell Medicine to enroll 80 people with SSD and 80 people with MDD. These individuals will be stratified into high and low SIB groups within each diagnostic group based on

Columbia Suicide Severity Rating Scale (C-SSRS; 40 per SIB group/diagnosis). 20 Healthy Volunteers will be enrolled to provide normative imaging data. Those in the high SIB group will have at least one lifetime actual or aborted or interrupted suicide attempt and a history of preparatory acts for suicide attempt over the past 3

years or 2+ lifetime suicide attempts. Those in the low SIB group will have at most passive suicidal ideation lifetime. Participants will receive interviews, questionnaire measures of impulsivity (including urgency), cognitive testing, and an MRI scan. This approach will allow us to his approach will allow us to highlight that

there is higher negative urgency (Hypothesis 1), lower fMRI BOLD activation in specific neurocircuits (Hypothesis 2), and lower cortical thickness (Hypothesis 3) in those with high SIB transdiagnostically. Moreover, in exploratory analyses we will examine the relationship between SIB and resting state functional

connectivity (RSFC) in urgency-related neurocircuitry in both SSD and MDD. We will determine the neural circuits affected in transdiagnostic patients with elevated NU, identifying the ideal regions to target using neuromodulation and other neuroscience-informed therapies, with the aim of reducing NU and ultimately, SIB.

By establishing the relationship between NU in transdiagnostic populations beyond SSD, we will determine whether urgency related interventions could be effective in a larger cohort of patients.