Investigating the neurocognitive correlates of suicidal risk in middle-aged and older adults with major depression

Suicide rates in middle-aged and older adults are alarmingly high, and research on suicide prevention in this population is urgently needed (Okolie et al., 2017). The 2021 NIMH Strategic Plan for Research (National Institute of Mental Health, 2021) prioritizes a focus on the identification of biomarkers of mental illness, including suicidal ideation and behavior. Understanding the neurobiological processes underlying suicidal ideation and behavior may help identify targets for intervention and ultimately lead to reduction in suicide risk.

In the current issue of International Psychogeriatrics, Jordan et al. (2020) investigated neurocognitive markers of passive suicidal ideation (PSI) in middle-aged and older adults with major depression. The authors examined whether aging adults with passive suicidal ideation (PSI) (e.g., thoughts that life is not worth living, death wishes) (n = 18) exhibited more impaired cognitive flexibility and inhibitory ability compared to aging adults without suicidal ideation (n = 22). Cognitive flexibility was defined as “the ability to shift attention in the context of changing demands of a task,” whereas inhibitory ability was defined as “the ability to inhibit a dominant, automatic, or prepotent response.” The authors also evaluated whether neurocognitive differences associated with PSI were mediated by volumetric differences in regions of the prefrontal cortex. The sample consisted of 40 community-dwelling, right-handed, 50 years old or older, with MDD or comorbid MDD/GAD according to DSM-IV-TR, and without any significant cognitive impairment (i.e., MMSE < 24).

The findings demonstrated that participants with PSI had worse cognitive flexibility and slower inhibitory ability than those without suicidal ideation. There were no significant differences between the two groups in any other neurocognitive domain, suggesting that the results were due to an effect specific to these processes rather than a more general impairment of cognitive function. The structural neuroimaging results showed significant differences in only one region of interest, the left midfrontal gyrus (MFG), which was larger in participants with PSI compared to those without. However, volume of the left MFG was not significantly associated with either cognitive flexibility or inhibitory ability.

Strengths of the study include its focus on an understudied group, i.e., middle-aged and older adults with PSI; a granular approach to measuring executive dysfunction; a focus on neurocognitive markers [neuropsychological and Magnetic Resonance Imaging (MRI) measures]; and a clinically important hypothesis of evaluating cognitive control in suicidal ideation in this population.

The focus of this study on aging adults with passive suicidal ideation (PSI) is clinically and heuristically important. Although the utility of suicidal ideation in predicting suicidal behavior has been challenged (Barak, 2022), PSI in older adults is an important clinical feature (van Orden et al., 2015) associated with similar history of suicidal behavior and hopelessness compared to those with active SI (Jordan et al., 2020). By addressing PSI, the authors fill a gap on the continuum between psychiatrically healthy older adults and those with overt suicidal behavior, which may provide important information about early signs of risk and potential targets for early intervention.

The granular approach taken by Jordan and colleagues to measuring executive dysfunction also provides insight into potential targets for new interventions. Using two behavioral measures for each construct (i.e., time to completion and error rate), the authors provide a broad examination of cognitive flexibility and inhibitory ability. This approach leads to a nuanced understanding of these two processes that could not have been derived from a single measure in isolation: whereas middle-aged and older adults with PSI exhibited deficits in cognitive flexibility that were characterized by both greater effort and lower accuracy, the deficits in inhibition were specific to effort. This suggests that in contrast to cognitive flexibility, which is both more impaired and more effortful in individuals with PSI compared to those without, inhibition is “more effortful but otherwise intact.” If these findings are replicated, new psychosocial interventions for PSI may focus on training of new skills such as cognitive reappraisal, which relies heavily on the use of cognitive flexibility. In contrast, they might focus less on teaching skills related to inhibition of negative thoughts and instead focus on reducing the effort required to utilize it—e.g., by providing plentiful opportunities for practice.

Another strength of the current study is the use of both neuropsychological and structural brain measures. In addition to MRI-based measures of functional connectivity, which the authors describe as an avenue for future research, their research could be complemented by direct measures of neural function. Electroencephalography (EEG)-derived measures such as event-related potentials offer a less invasive, less expensive, and potentially more temporally sensitive measure than structural or functional brain measures that allow for a fine-grained analysis of the time-course specific executive functions. Studies using the Wisconsin Card Sorting Test, for instance, have identified both an earlier event-related potential measure of cognitive flexibility indexing attentional orienting efficiency (the P3a) and a later measure indexing set-shifting (the posterior switch positivity) (Lange et al., 2017). Recent work from other groups has demonstrated that the no-go P300, an event-related potential index of inhibitory control, is associated with depression among older adults reporting high levels of loneliness (Brush et al., 2022) and is blunted in individuals with a history of suicide attempts compared to those without (Yoon et al., 2022). Incorporating event-related potential measures like these into future studies would expand on the work of Jordan and colleagues to further elucidate neurobiological abnormalities underlying the executive dysfunction observed in mid- and late-life suicidality.

The explanatory power of the neurocognitive indices described by Jordan and colleagues might also be enhanced by including measures of other neurobiological systems such as the positive valence systems (PVS) described in the National Institute of Mental Health’s Research Domain Criteria (RDoC) (Morris and Cuthbert, 2022). Aspects of PVS function including reward responsiveness, reward valuation, and reward learning have shown evidence of disruption among individuals with histories of suicidality, with the majority of research in reward learning having been conducted specifically in older adults (Auerbach et al., 2022). In probabilistic reversal learning tasks, for instance, older adults with a history of suicide attempts discount history of reward and punishment to a greater degree than their peers (Dombrovski et al., 2010) and are characterized by abnormal activation of corticostriatothalamic circuits (Dombrovski et al., 2013). Incorporating measures of PVS function alongside measures of executive function in future research would provide a richer understanding of the ways in which multiple neurobiological systems interact to heighten or mitigate risk for suicide in middle-aged and older adults.

The findings of this study provide an exciting direction for future research into mechanisms of late-life suicide. Jordan et al’s study highlights the critical relationship of suicidal ideation with cognitive control, a set of processes associated with successful emotion regulation. Their findings align with prior work emphasizing the role of increased emotion reactivity and decreased emotion regulation in suicidal ideation and behavior in middle-aged and older adults (Beghi et al., 2013; Kiosses et al., 2014; Naifeh et al., 2022; Nordentoft, 2007; Seidlitz et al., 2001). However, the relationship of emotion reactivity with emotion regulation is complex and not well understood. Future research may evaluate how interactions between emotional reactivity and aspects of cognitive control involved in emotion regulation contribute to increased or decreased suicide risk in middle-aged and older adults.

In sum, the work presented by Jordan et al examines neurocognitive markers of passive suicidal ideation in middle-aged and older adults and demonstrates specific deficits related to cognitive flexibility and inhibition. Future research may expand the current findings and help better understand the neurobiological correlates of suicidal ideation and behavior and provide potential new avenues for intervention in this understudied population.