Translating Interventional Neuroscience to Suicide: It's About Time.

Despite significant advances in psychiatric and psychological treatment over the last 30 years, suicide deaths have increased. Unfortunately, neuroscience insights have yielded few translational interventions that specifically target suicidal thoughts and behaviors. In our view, this is attributable to two factors. The first factor is our limited integration of neurocircuitry models with contemporary suicide theory. The second challenge is inherent to the variable nature of suicide risk over time. Few interventional neuroscience studies evaluate how temporal fluctuations in risk affect treatment, despite evidence that temporality is a key component distinguishing suicide phenotypes. To wit, individual variability in risk trajectories may provide different treatment targets to engage as a patient moves between suicidal ideation and attempt. Here, we first review contemporary ideation-to-action theories of suicide from a neurobiological perspective, focusing on valence and executive function circuits and the key role of state-induced (e.g., within stressful contexts) functional modulation on longitudinal risk trajectories. We then describe neural correlates of suicide reduction following various interventions, ranging from circuit specific (i.e., transcranial magnetic stimulation) to broader pharmacological (i.e., ketamine, lithium) to psychological (i.e., brief cognitive therapy). We then introduce novel strategies for tracking risk in naturalistic settings and real time using ecological momentary interventions. We provide a critical integration of the literature focusing on the intersection between targets and temporality, and we conclude by proposing novel research designs integrating real-time and biologically based interventions to generate novel strategies for future suicide reduction research.