Alterations in Functional Brain Activity as Predictors of Suicide Risk in Late-Life Depression: A Systematic Review

Abstract

Introduction: Late-life depression (LLD) is a significant risk factor for suicide in older adults, yet clinical assessments for suicidality are often limited by subjective reporting and lack of predictive validity. Functional neuroimaging has highlighted overlapping alterations in neurocircuitry underlying emotional processing, decision-making and cognitive control between LLD and suicidality, potentially serving as predictors of suicide risk. However, no review to date has synthesized this evidence in the context of LLD.

Methods: A systematic search was conducted in Ovid MEDLINE, Embase and APA PsycInfo databases, following PRISMA guidelines. Eligible studies included older adults (≥55 years) with clinically defined LLD, validated measures of suicidality, and fMRI data. Of 1829 articles identified, eight studies met the inclusion criteria. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale.

Results: Functional alterations were observed in frontostriatal and limbic circuits. Resting-state studies reported disrupted connectivity within/between the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), caudate nucleus, and amygdala. Task-based studies revealed blunted ventromedial prefrontal responses to reward and heightened frontal operculum activation during socioemotional tasks among suicide attempters compared to depressed non-suicidal and healthy individuals.

Discussion: Disruptions in functional brain activity in LLD that contribute to suicide risk may reflect impaired decisionmaking, reward valuation, cognitive control, and affective dysregulation. Differences in functional activation and connectivity may distinguish suicidal ideation from suicide attempts, though further studies with larger, more diverse samples and longitudinal designs are needed to clarify this.

Conclusion: Functional neuroimaging reveals convergent patterns of dysregulation in key brain networks associated with suicide risk in LLD. These findings highlight the potential for imaging-informed models of suicide risk stratification and targeted neuromodulation. Longitudinal and interventional studies are needed to refine predictive biomarkers and improve clinical utility.