Functional Brain Dysregulation Associated with Psychological Pain in Suicide Attempters: A Systematic Review

Abstract

Introduction: Suicide is a major global health concern causing over 700,000 annual deaths. Despite research efforts and clinical need, means of stratifying individuals at the highest risk of suicide attempt remain insufficient. Psychological pain is a key feature of ideation-to-action theory and involves a distinct neural network. However, alterations in the neurocircuitry related to psychological pain between suicide attempters (SA) and suicide ideators (SI) have not been firmly established. Such alterations may serve as a biomarker capable of risk stratification and informing therapeutic targets. Thus, this review sought to identify if consistent functional brain alterations associated with psychological pain exist in SA relative to SI.

Methods: A search strategy with terms related to suicide and psychological pain was conducted in Embase, APA PsycInfo, and Ovid MEDLINE databases without any limits. Studies were screened for use of functional neuroimaging, psychological pain measures, and comparisons between adult SA and SI with mood disorders. Relevant data was extracted from six included studies, and study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale adapted for cross-sectional studies.

Results: The anterior cingulate cortex, insula, orbitofrontal cortex, and thalamus, which are central to the experience of psychological pain, showed consistent dysregulation in SA compared to SI across a range of neuroimaging paradigms. Dysregulation in these regions was consistently correlated with psychological pain levels and suicide attempts, although directionality varied. Comparisons of self-reported psychological pain in SA relative to SI were inconsistent.

Discussion: Brain function in SA may be characterized by alterations in a network of regions associated with psychological pain. This dysregulation indicates impairments in processing and top-down control of negative emotion, decision-making, social cognition, and pain avoidance. Such impairments may make individuals more vulnerable to suicide attempt.

Conclusion: Our findings provide insight into functional brain dysregulation associated with psychological pain that may mediate the transition from ideation to attempt. Further research is needed to clarify the generalizability of these findings and to refine a biomarker of suicide risk. Additional longitudinal research is required to assess whether such brain dysregulation predicts future attempt in SI and whether it represents a therapeutic target.