Table 1.

Suicide literature related to the Research Domain Criteria (RDoC) matrix.¹

Negative Valence Systems: “primarily responsible for responses to aversive situations or context, such as fear, anxiety, and loss”
Construct	Definition	Examples	Sample References	Unit of Analysis
Loss	“A state of deprivation of a motivationally significant con- specific, object, or situation. Loss may be social or non- social and may include permanent or sustained loss of shelter, behavioral control, status, loved ones, or relationships. The response to loss may be episodic (e.g., grief) or sustained.”	Interpersonal loss	Bagge, Glenn, & Lee, 2013; Cheng, Chen, Chen, & Jenkings, 2000; Yen et al., 2005	Self-report
		Employment or financial loss	Cheng et al., 2000; Classen & Dunn, 2012	Self-report
		Loss of personal health	Cavanagh, Owens, & Johnstone, 1999; Cheng et al., 2000	Self-report
		Potential Mediators	Sample References	Unit of Analysis
		Loneliness, isolation, decreased belongingness	Zuroff, Fournier, & Moskowitz, 2007 (also see Social Processes)	Self-report
		Guilt and humiliation	Hendin, Maltsberger, Lipschitz, Haas, & Kyle, 2001	Self-report
		Potential Moderators	Sample References	Unit of Analysis
		Negative attributional style	Kleiman, Riskind, Stange, Hamilton, & Alloy, 2014	Self-report
		Perfectionism	Hewitt, Caelian, Chen, & Flett, 2014	Self-report
		Problem solving deficits	Grover et al., 2009	Self-report
Construct	Definition	Examples	Sample References	Unit of Analysis
Sustained threat	“An aversive emotional state caused by prolonged (i.e., weeks to months) exposure to internal and/or external condition(s), state(s), or stimuli that are adaptive to escape or avoid. The exposure may be actual or anticipated; the changes in affect, cognition, physiology, and behavior caused by sustained threat persist in the absence of the threat, and can be differentiated from those changes evoked by acute threat.”	Childhood abuse and neglect	Joiner et al., 2007; Sarchiapone, Carli, Cuomo, & Roy, 2007; Spokas, Wenzel, Stirman, Brown, & Beck, 2009; Ystgaard, Hestetun, Loeb, & Mehlum, 2004	Self-report
		Peer victimization and bullying in youth	Geoffroy et al., 2016; Klomek, Marrocco, Kleinman, Schonfeld, & Gould, 2007	Self-report
		Chronic stress (e.g., interpersonal, occupational)	Baumert et al., 2014; Pettit, Green, Grover, Schatte, & Morgan, 2011	Self-report
		Potential Mediators	Sample References	Unit of Analysis
		Emotion regulation difficulties	Gordon et al., 2015	Self-report
		Hopelessness	Spokas et al., 2009	Self-report
		Engagement in risky behaviors	Dube et al., 2001	Self-report
		Re-victimization	Lee, 2015	Self-report
		Alterations in stress- response system	Turecki & Brent, 2016	Physiology
		Potential Moderators	Sample References	Unit of Analysis
		(See potential moderators of loss construct)
		Genetic moderators:
		Serotonin   transporter gene   (5-HTTLPR)	Roy, Hu, Janal, & Goldman, 2007; Shinozaki et al., 2013	Genes (× environment)
		Serotonin gene   HTR2A	Ben-Efraim, Wasserman, Wasserman, & Sokolowski, 2013; Brezo et al., 2010	Genes (× environment)
		Brain-derived   neurotrophic   factor (BDNF)	Perroud et al., 2008	Genes (× environment)
		Corticotropin-   releasing hormone   receptor 1   (CRHR1)	Ben-Efraim, Wasserman, Wasserman, & Sokolowski, 2011	Genes (× environment)
Construct	Definition	Examples	Sample References	Unit of Analysis
Frustrative nonreward	“Reactions elicited in response to withdrawal or prevention of reward, i.e., by the inability to obtain positive rewards following repeated or sustained efforts.”	Psychiatric disorders characterized by aggression, anger, and irritability (e.g., impulse- control, substance use, antisocial personality, and intermittent explosive disorders)2	Evren, Cinar, Evren, & Celik, 2011; Nock, Hwang, Sampson, & Kessler, 2010; Nock et al., 2014;	Self-report
		Trait aggression, anger, irritability	Borges et al., 2010; Hawkins et al., 2014; Swogger, Van Orden, & Conner, 2014	Self-report
		Potential Mediators	Sample References	Unit of Analysis
		Emotion regulation difficulties	Ammerman, Kleiman, Uyeji, Knorr, & McCloskey, 2015	Self-report
		Perceived burdensomeness and lack of belongingness	Hawkins et al., 2014	Self-report
Construct	Definition	Examples	Sample References	Unit of Analysis
Acute and potential threat	Acute threat (“fear”): “Activation of the brain’s defensive motivational system to promote behaviors that protect the organism from perceived danger.” Potential threat (“anxiety”): “Activation of a brain system in which harm may potentially occur but is distant, ambiguous, or low/uncertain in probability, characterized by a pattern of responses such as enhanced risk assessment (vigilance).”	Fear disorders	Borges et al., 2010; Nock, Hwang, et al., 2010	Self-report
		Panic attacks	Yaseen, Chartrand, Mojtabai, Bolton, & Galynker, 2013	Self-report
		Anxiety disorders	Borges et al., 2010; Nock, Borges, Bromet, Alonso, et al., 2008; Nock, Hwang, et al., 2010	Self-report
		Fear-potentiated startle response (but not anxiety- potentiated startle)	Ballard et al., 2014	Physiology
Positive Valence Systems (PVS): “Primarily responsible for responses to positive motivational situations or contexts, such as reward seeking, consummatory behavior, and reward/habit learning”
Construct nonspecific (i.e., tied to PVS but not to a specific construct with this domain)	Definition	Examples	Samples References	Unit of Analysis
	(see PVS definition above)	Anhedonia	Fawcett et al., 1990; Nock & Kazdin, 2002	Self-report
		Psychiatric disorders characterized by hyperresponsiveness of the reward system, such as substance use and impulse-control disorders	Borges et al., 2010; Nock, Hwang, et al., 2010; Vijayakumar, Kumar, & Vijayakumar, 2011; Wong, Cheung, Conner, Conwell, & Yip, 2010	Self-report
Construct	Definition	Examples	Sample References	Unit of Analysis
Approach motivation	“Involving mechanisms/processes that regulate the direction and maintenance of approach behavior…can be directed toward innate or acquired cues… implicit or explicit goals”	Indifference to reward magnitude (reward valuation)	Liu, Vassileva, Gonzales, & Martin, 2012	Behavior
		Reduced willingness to work for a reward	Auerbach, Millner, Stewart, & Esposito, 2015	Behavior
Initial and sustained responsiveness to rewards	“Mechanisms and processes associated with hedonic responses—as reflected in subjective experiences, behavioral responses, and/or engagement of the neural systems to a positive reinforcer—and culmination of reward seeking.”	Weak paralimbic responsiveness to expected rewards	Dombrovski, Szanto, Clark, Reynolds, & Siegle, 2013	Circuits
Reward learning	“Process by which organisms acquire information about stimuli, actions, and contexts that predict positive outcomes, and by which behavior is modified when a novel reward occurs or outcomes are better than expected.”	Difficulty flexibly adapting to new information to increase probability of rewards:
		Perseverating on   previously   rewarding stimuli   even when no   longer   advantageous	Dombrovski et al., 2013	Behavior
		Switching away   from newly   rewarding stimuli   too quickly	Dombrovski et al., 2010	Behavior
Cognitive Systems: “responsible for various cognitive processes” (see Constructs for examples)
Construct	Definition	Examples	Sample References	Unit of Analysis
Declarative memory	“Acquisition or encoding, storage and consolidation, and retrieval of representations of facts and events.”	Recalling past events in an overgeneralized style with fewer vivid details (e.g., Autobiographical Memory Test)	Arie, Apter, Orbach, Yefet, & Zalsman, 2008; Pollock & Williams, 2001; Williams et al., 1996	Behavior
		Delayed recall	Richard-Devantoy, Berlim, & Jollant, 2015	Behavior
Working memory	“Active maintenance and flexible updating of goal/task relevant information (items, goals, strategies, etc.) in a form that has limited capacity and resists interference.”	Overall working memory deficits (e.g., N-Back Task, Weschler Memory Scale)	Kim, Jayathilake, & Meltzer, 2003; Richard-Devantoy et al., 2015	Behavior
Cognitive control	“System that modulates the operation of other cognitive and emotional systems, in the service of goal-directed behavior, when prepotent modes of responding are not adequate to meet the demands of the current context. Additionally, control processes are engaged in the case of novel contexts, where appropriate responses need to be selected from among competing alternatives.”	Executive attention3 or attention control deficits (e.g., Stroop Task)	Keilp, Gorlyn, Oquendo, Burke, & Mann, 2008; Keilp et al., 2013; Keilp et al., 2001	Behavior
		Making disadvantageous choices (e.g., Iowa Gambling Task)	Jollant et al., 2005; Jollant et al., 2007	Behavior
		Difficulty inhibiting poor responses (e.g., Go/No- Go Test)	Westheide et al., 2008	Behavior
		Decreased activation for disadvantageous choices in the lateral orbitofrontal and occipital cortices (e.g., Iowa Gambling Task)	Jollant et al., 2010	Circuits
Perception	“Processes that perform computations on sensory data to construct and transform representations of the external environment, acquire information from, and make predictions about, the external world, and guide action.”	Auditory verbal hallucinations	Fujita et al., 2015; Harkavy-Friedman et al., 2003; Nordentoft et al., 2002	Self-report
		Visual acuity	Rim, Lee, Sung, Chung, & Kim, 2015	Behavior
		Chronic pain	Calati, Bakhiyi, Artero, Ilgen, & Courtet, 2015; Hooley, Franklin, & Nock, 2014	Self-report
		Higher pain tolerance (e.g., cold pressor task)	Ribeiro et al., 2014	Behavior
Language	“System of shared symbolic representations of the world, the self and abstract concepts that supports thought and communication.”	Speech production patterns, acoustic effects (such as monotonous and repetitive phrasing), and voice quality	Cummins et al., 2015; Silverman & Silverman, 2006	Behavior
Social Processes: “mediate responses to interpersonal settings of various types, including perception and interpretation of others’ actions”
Construct	Definition	Examples	Sample References	Unit of Analysis
Affiliation and attachment	“Affiliation is engagement in positive social interactions with other individuals. Attachment is selective affiliation as a consequence of the development of a social bond. Affiliation and Attachment are moderated by social information processing (processing of social cues) and social motivation. Affiliation is a behavioral consequence of social motivation and can manifest itself in social approach behaviors.”	Feelings of loneliness and lack of social belonging	Burke, Hamilton, Ammerman, Strange, & Alloy, 2016; Fisher, Overholser, Ridley, Braden, & Rosoff, 2015; Wichstrom, 2000	Self-report
		Perceived burdensomeness	Brown, Dahlen, Mills, Rick, & Biblarz, 1999; Van Orden, Lynam, Hollar, & Joiner, 2006	Self-report
		Avoidant attachment style	Grunebaum et al., 2010	Self-report
		Insecure attachment style	Sheftall, Schoppe-Sullivan, & Bridge, 2014	Self-report
		Family responsibility, including having children at home4	Oquendo et al., 2005; Qin & Mortensen, 2003	Self-report
		School connectedness4	Sampasa-Kanyinga & Hamilton, 2016	Self-report
		Religious affiliation4	Dervic et al., 2004	Self-report
Perception and understanding of self	“The processes and/or representations involved in being aware of, accessing knowledge about, and/or making judgments about the self. These processes and representations can include current cognitive or emotional internal states, traits, and/or abilities, either in isolation or in relationship to others, as well as the mechanisms that support self-awareness, self-monitoring, and self-knowledge.”	Low self-esteem, low self-efficacy, low self- concept	Bolton, Pagura, Enns, Grant, & Sareen, 2010; Lewinsohn, Rohde, Seeley, & Baldwin, 2001; Wichstrom, 2000	Self-report
		High self-consciousness, self-criticism, or self- blame	Bolton et al., 2010; Wiklander et al., 2012; Yen & Siegler, 2003	Self-report
		Implicit self- identification with death/suicide (assessed via the death/suicide Implicit Association Test; d/s IAT)	Barnes et al., 2016; Nock, Park, et al., 2010	Behavior
Perception and understanding of others	“The processes and/or representations involved in being aware of, accessing knowledge about, reasoning about, and/or making judgments about other animate entities, including information about cognitive or emotional states, traits or abilities.”	No examples have been examined in relation to suicidal behaviors
Social communication	“A dynamic process that includes both receptive and productive aspects used for exchange of socially relevant information. Social communication is essential for the integration and maintenance of the individual in the social environment.”	Increased neural activity to angry faces, potentially indexing sensitivity to signals of anger or social disapproval	Jollant et al., 2008; Pan et al., 2013	Circuits
		Autism spectrum disorders, in which social communication deficits are prominent	Hannon & Taylor, 2013	Self-report
Arousal and Regulatory Systems: “responsible for generating activation of neural systems as appropriate for various contexts, and providing appropriate homeostatic regulation of such systems as energy balance and sleep”
Construct	Definition	Examples	Sample References	Unit of Analysis
Sleep- wakefulness	“Sleep and wakefulness are endogenous, recurring, behavioral states that reflect coordinated changes in the dynamic functional organization of the brain and that optimize physiology, behavior, and health.”	Psychiatric disorders with core disturbances in sleep, such as mood disorders and posttraumatic stress disorder	Nock, Borges, & Ono, 2012; Nock, Hwang, et al., 2010	Self-report
		Sleep difficulties, including insomnia, hypersomnia, nightmares, and poor sleep quality (e.g., nonrestorative sleep)	Bernert, Turvey, Conwell, & Joiner, 2014; Pigeon, Pinquart, & Conner, 2012	Self-report
		Dysfunction in rapid eye movement (REM); lower sleep efficiency; longer sleep latency (assessed via EEG)	Agargun & Cartwright, 2003; Sabo, Reynolds, Kupfer, & Berman, 1991	Physiology
Circadian rhythms	“Endogenous self-sustaining oscillations that organize the timing of biological systems to optimize physiology and behavior, and health.”	Diurnal variation5	Erazo, Baumert, & Ladwig, 2004; Preti & Miotto, 2001
		Seasonal variation5	Altamura, VanGastel, Pioli, Mannu, & Maes, 1999; Erazo et al., 2004
Arousal	“Sensitivity of the organism to stimuli, both external and internal.”	Psychiatric disorders with core symptoms of hyperarousal, such as psychomotor agitation in depression, increased goal-directed behavior in bipolar disorder, hypervigilance in posttraumatic stress disorder	Nock et al., 2012; Nock, Hwang, et al., 2010	Self-report
		Agitated affective states6	Busch, Fawcett, & Jacobs, 2003; Hendin et al., 2001; Sadeh & McNiel, 2013	Self-report
		Emotion reactivity6	Nock, Wedig, Holmberg, & Hooley, 2008 (SI/SA)	Self-report

¹Definitions for each construct are drawn from the RDoC Matrix website: https://www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml

²As defined by RDoC, aggression is a heterogeneous construct. In the RDoC framework, different forms of aggression are categorized based on their distinct antecedents and motivations (NIMH, 2011). For instance, Negative Valence: frustrative nonreward is distinguished from defensive aggression (categorized under Negative Valence: acute threat) and offensive (proactive) aggression (categorized under the Social Processes domain). Unfortunately, previous suicide research lacks the specificity needed to make these fine-grained distinctions. Moreover, there remains debate about where aggression should be most appropriately included in the matrix. For the purposes of this review, we discuss aggression within Negative Valence: frustrative nonreward, but recognize that this may not be the most accurate classification.

³Executive attention falls under cognitive control (instead of attention) due to its involvement in input selection (within the goal selection, updating, and representation subconstruct).

⁴Indicates examples of factors that decrease risk for suicidal behaviors.

⁵These examples are proxies for circadian rhythms and therefore no specific unit of analysis is indicated. Of note, the Arousal and Regulatory Systems workgroup chose not to include seasonal oscillations within the circadian rhythms construct, noting there is “little evidence to support the presence of seasonal oscillations in the human mammal” (NIMH, 2012). However, given the seasonal patterns in rates of suicide deaths, we decided this was relevant to include in our review.

⁶These studies confound arousal and valence and therefore it is unclear how much risk is conferred by increased arousal specifically.