Poster No:
396
Submission Type:
Abstract Submission
Authors:
Aaima Cheema1, Jessica Sah2, Oghogho Iyekekpolor2, Sakina Rizvi3, Sidney Kennnedy4, Katharine Dunlop3
Institutions:
1University of Toronto, Toronto, ON, 2University of Toronto, Toronto, Ontario, 3Centre for Depression and Suicide Studies, Unity Health Toronto, Toronto, Ontario, 4University Health Network, Toronto, Ontario
First Author:
Co-Author(s):
Sakina Rizvi
Centre for Depression and Suicide Studies, Unity Health Toronto
Toronto, Ontario
Katharine Dunlop
Centre for Depression and Suicide Studies, Unity Health Toronto
Toronto, Ontario
Introduction:
Suicide is the tenth leading cause of death in North America, with major depressive disorder (MDD) being the most common mental disorder among suicide [2]. Although suicide attempt risk factors exist, none prospectively predict attempt in individuals diagnosed with MDD [6]. One way to identify prognostic factors is by understanding how certain symptoms are biologically correlated with suicidal thoughts and behaviors (STB). Prior studies suggest that irritability predicts increased risk for suicidality in MDD [1,3] and both are associated with interpersonal conflict [8]. While the clinical link between irritability and STB is well-established, little is known about the neurobiological link. In MDD, understanding the neurobiological link between irritability and STBs may help identify risk factors. Task-based functional magnetic resonance imaging (fMRI) assessing irritability or suicidality separately suggest a common neural circuit localized to regions involved in social cognition, emotion and executive function [5,7]. However, no neuroimaging studies have examined their relationship together in MDD. This study aims to identify differences in the behavioral and neural correlates of irritability in MDD individuals with suicidal ideation and a recent suicide attempt (MDD+SA), relative to MDD individuals with suicidal ideation and no history of attempt (MDD-SA), and healthy controls (HC).
Methods:
This pilot study included 18 participants (ages 18-65, 13 female): ten HC and eight MDD participants with STB. Participants completed questionnaires assessing suicidality, irritability, and depression severity, and two validated task-based fMRI paradigms. The first task induced negative affect like irritability via social exclusion (Cyberball Task) [9], and the second evaluates retaliatory aggression against social excluders (Dictator Task) [10]. fMRI data was preprocessed using FSL [4], and included distortion correction, affine motion correction, smoothing, coregistration and normalization to the MNI template. Two first-level event-related general linear models (GLM) modeled task-related activity for each task. We used GLMs, controlling age, sex, and depression severity, to test for between-group differences.
Results:
Task-based behavioral data for HCs showed, social exclusion increased irritability (W=15.00, p=.05). Both baseline irritability and irritability change correlated with retaliation against excluders (Baseline Spearman's ρ=0.68 p=.03; Change ρ=.66, p=.04). Relative to HC, MDD participants had significantly greater irritability at baseline (U=3.00, p=.001), after inclusion (U=4.00, p<0.001) and exclusion (U=8.00, p=.004). Irritability worsened from inclusion to exclusion at trend (W=25.50, p=.06). Those with a higher capacity for suicide punished excluders at higher rates (ρ=0.76, p=.04). Across all groups, social exclusion activated the anterior cingulate cortex (ACC), precuneus, and posterior cingulate cortex (p<0.05). Compared to HC, irritability in MDD was linked to increased ACC and dorsomedial prefrontal cortex (DMPFC) activity. During retaliation, irritability in MDD negatively correlated with ACC and DMPFC activity. In contrast, forgiveness of excluders was positively correlated with dorsolateral prefrontal cortex (DLPFC) activity (p<0.05).
Conclusions:
In MDD, highly irritable individuals retaliated more frequently against Cyberball excluders, with greater retaliation following social exclusion linked to higher suicide risk. This study also identifies prefrontal activity in MDD is linked to irritability. These findings provide the first neurobiological insights into the relationship between irritability and suicidality in MDD, suggesting that irritability could serve as a valuable behavioral target for suicide risk assessment and intervention. The identified brain targets could lead to the development of innovative neurostimulatory treatments for STBs in individuals with irritability.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Emotion, Motivation and Social Neuroscience:
Social Cognition
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Keywords:
Affective Disorders
FUNCTIONAL MRI
Limbic Systems
Social Interactions
Other - Irritability; Neurobiology; Depression; Major Depressive Disorder; Suicide
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Task-activation
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
Functional MRI
Structural MRI
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
FSL
Free Surfer
LONI Pipeline
Provide references using APA citation style.
[1] Conner, K. R. (2004). The association of irritability and impulsivity with suicidal ideation among 15- to 20-year-old males. Suicide and Life-Threatening Behavior, 34(4), 363–373.
[2] Fazel, S. (2020). Suicide. The New England Journal of Medicine, 382(3), 266–274.
[3] Husky, M. (2017). Predictors of daily life suicidal ideation in adults recently discharged after a serious suicide attempt: A pilot study. Psychiatry Research, 256, 79–84.
[4] Kundu, P. (2013). Integrated strategy for improving functional connectivity mapping using multiecho fMRI. Proceedings of the National Academy of Sciences of the United States of America, 110(40), 16187–16192.
[5] Mwilambwe-Tshilobo, L. (2021). Social exclusion reliably engages the default network: A meta-analysis of Cyberball. NeuroImage, 227, 117666.
[6] Nugent, A. C. (2019). Research on the pathophysiology, treatment, and prevention of suicide: Practical and ethical issues. BMC Psychiatry, 19, 332.
[7] Schmaal, L. (2020). Imaging suicidal thoughts and behaviors: A comprehensive review of 2 decades of neuroimaging studies. Molecular Psychiatry, 25(2), 408–427.
[8] Staebler, K. (2009). Emotional responses in borderline personality disorder and depression: Assessment during an acute crisis and 8 months later. Journal of Behavior Therapy and Experimental Psychiatry, 40(1), 85–97.
[9] Williams, K. D. (2006). Cyberball: A program for use in research on interpersonal ostracism and acceptance. Behavior Research Methods, 38(1), 174–180.
[10] Will, G.-J. (2016). Neural correlates of retaliatory and prosocial reactions to social exclusion: Associations with chronic peer rejection. Developmental Cognitive Neuroscience, 19, 288–297.
No