Catalytic Reaction Model of Suicide

Abstract

Suicide is a devastating outcome of unresolved issues that affect mental health, general wellbeing and socioeconomic stress. The biology of suicidal behavior is still poorly understood, although progress has been made. Suicidal behavior runs in families and genetic studies have provided initial glimpses into potential genes that contribute to suicide risk. Here, we attempt to unify the biology and behavioral dimensions into a model that can guide research in this area. The proposed model envisions suicidal behavior as a catalytic reaction that may result in suicide depending on the conditions, analogously to enzyme catalysis of chemical reactions. A wide array of substrates or reactants, such as hopelessness, depression, debilitating illnesses and diminished motivation can mobilize suicidal thoughts and behaviors (STBs), which can then catalyze the final step/act of suicide. Here, we focus on three biological substrates in particular: threat assessment, motivation to engage in life and impulsivity. Genetic risk factors can affect each of these processes and tilt the balance toward suicidal behavior when existential crises (real or perceived) emerge such as loss of a loved one, sudden changes in social status or serious health issues. Although suicide is a uniquely human behavior, many of the fundamental biological processes are evolutionarily conserved. Insights from animal models may help to shape our understanding of suicidal behavior in man. By examining counterparts of the major biological processes in other organisms, new ideas about the role of genetic risk factors may emerge along with possible therapeutic interventions or preventive measures.

Keywords: diminished motivation; impulsivity; suicidal ideation (SI); suicide; threat assessment.

Figure 1

Catalytic reaction model of suicide. In a chemical reaction (upper panel), reactants may combine slowly in the absence of a catalyst, which interacts with both reactants, lowers the energy barrier to the chemical reaction and catalyzes formation of product. Conditions and concentrations of reactants along with the activity of the catalyst determine the rate of the reaction. By analogy, in the lower left panel, various reactants (in red font) combine to determine the catalytic activity of suicidal ideation, which then lowers the “energy” barrier for suicidal behaviors (intention, planning, attempts and completion). The lack of arrows between a pictured reactant and suicidal ideation indicates that at this particular time those factors are manageable and do not contribute to the ongoing suicide reaction. The rate of the suicidal reaction is also determined by environmental conditions (black font) such as stressors or the presence of a psychiatric condition and how well it is being managed. The font size of the reactants and conditions reflects their “concentrations” or “energy” – determined by the intensity, frequency and duration of their effects. Genetic variation (blue font) affects the reaction at several levels by: (1) specifying vulnerability to psychiatric disorders, (2) determining resiliency or acuity in the face of adverse childhood experiences (ACEs) and (3) affecting the emergence and intensity of hopelessness, impulsivity, diminished motivation, etc. in response to changes in the environment. Genetic variants will also affect how a person responds to stressors. As discussed in the next section, genes (e.g., those involved in insulin signaling) affect motivation states, threat assessment (e.g., neuropeptide Y) and impulsivity. In this way, a genetic risk variant can act as a catalyst by lowering the “energy” barrier for expressing various reactants that give rise to STBs. The environment plays a role by affecting motivation (e.g., through reward availability), determining the level of external threat and shaping the context in which opposing behavioral decisions are made. The suicide reaction is dynamic and changes over time, including which risk genes are most important due to differential contributions by different reactants depending on changing circumstances. For example, in the panel at the lower right, the same person represented to the left has now received more effective treatment for their depression and has recently found a new job after a period of unemployment. These changing conditions might lessen feelings of hopelessness, increase a sense of security (a protective factor) and improve motivation to engage in life. Consequently, suicidal ideation is greatly reduced and may be eliminated with continuing progress. Nevertheless, certain levels of impulsivity may remain, and heightened threats may persist due to factors less amenable to change, e.g., ACEs. With lowered concentrations of reactants and a decrease in the catalytic activity of suicidal ideations, residual levels of threat or impulsivity may be tolerable. Suicidal behavior is depicted on a spectrum with arrows showing that some of the processes are reversible. Furthermore, the bidirectional arrows between reactants and suicidal ideation indicate that learned aspects of ideation can feedback to potentially increase feelings of hopelessness, further diminish motivation for enjoyable life activities, etc. The constellation of reactants that drive the reaction will differ between individuals and in relation to their dominance. For instance, a person with a severe debilitating medical condition who contemplates suicide may be primarily driven by feeling like a burden to their family, whereas the ideation of a suicide bomber may be dominated by cognitive control (making disadvantageous choices for political aims) or religious motivations (not depicted). Although two mental states of the individual are represented here, in reality, conditions, reactants and ideation are constantly fluctuating until a crisis is resolved. In our view, prevention should mainly focus on removing threats, promoting engagement in life and mindfulness training to recognize and stop impulsive override of logic. Finally, it will be important to address potential precipitating conditions such as a psychiatric disorder or stressful life events with medications, patient education, coping strategies and therapy as appropriate.