Currently, the diagnosis of mental disorders is based on clinical observation—identifying symptoms that tend to cluster together, determining when the symptoms appear, and determining whether the symptoms resolve, recur, or become chronic. However, the way that mental disorders are defined in the present diagnostic system does not incorporate current information from integrative neuroscience research, and thus is not optimal for making scientific gains through neuroscience approaches. It is difficult to deconstruct clusters of complex behaviors and attempt to link these to underlying neurobiological systems. Many mental disorders may be considered as falling along multiple dimensions (e.g., cognition, mood, social interactions), with traits that exist on a continuum ranging from normal to extreme. Co-occurrence of multiple mental disorders might reflect different patterns of symptoms that result from shared risk factors and perhaps the same underlying disease processes.

To clarify the underlying causes of mental disorders, it will be necessary to define, measure, and link basic biological and behavioral components of normal and abnormal functioning. This effort will require integration of genetic, neuroscience, imaging, behavioral, and clinical studies. By linking basic biological and behavioral components, it will become possible to construct valid, reliable phenotypes (measurable traits or characteristics) for mental disorders. This will help us elucidate the causes of the disorder, while clarifying the boundaries and overlap between mental disorders. In order to understand mental disorders in terms of dimensions and/or components of neurobiology and behaviors, it will be important to:

●       Initiate a process for bringing together experts in clinical and basic sciences to jointly identify the fundamental behavioral components that may span multiple disorders (e.g., executive functioning, effect regulation, person perception) and that are more amenable to neuroscience approaches.

●       Develop reliable and valid measures of these fundamental components of mental disorders for use in basic studies and in more clinical settings.

●       Determine the full range of variation, from normal to abnormal, among the fundamental components to improve understanding of what is typical versus pathological.

●       Integrate the fundamental genetic, neurobiological, behavioral, environmental, and experiential components that comprise these mental disorders.

Whereas conventional diagnostic systems incrementally revise and build upon their pre-existing paradigms, “RDoC is agnostic about current disorder categories.” Official documents explain this
feature, writing: “Rather than starting with an illness definition and seeking its neurobiological underpinnings, RDoC begins with current understandings of behavior-brain relationships and links them to clinical phenomena.”

Unlike conventional diagnostic systems, which typically rely on self-report and behavioral measures alone, the RDoC framework has the “explicit goal” of allowing investigators access to a wider
range of data. In addition to self-report measures or measure of behavior, RDoC also incorporates units of analysis beyond those found in the DSM — allowing RDoC to be informed by insights into genes, molecules, cells, circuits, physiology, and large-scale paradigms.

The RDoC framework consists of a matrix where the rows represent specified functional constructs (concepts representing a specified functional dimension of behavior) characterized in aggregate by the
genes, molecules, circuits, etc. used to measure it. Constructs are in turn grouped into higher-level domains of functioning, reflecting contemporary knowledge about major systems of emotion, cognition, motivation, and social behavior. Currently, there are five Domains in the RDoC matrix.

Negative Valence Systems

Systems primarily responsible for responses to aversive situations or context, such as fear, anxiety, and loss.

●      Responses to acute threat (Fear): Activation of the brain’s
defensive motivational system to promote behaviors that protect the organism
from perceived danger. Normal fear involves a pattern of adaptive responses to
conditioned or unconditioned threat stimuli (exteroceptive or interoceptive).
Fear can involve internal representations and cognitive processing, and can be
modulated by a variety of factors.

●      Responses to potential harm (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). These responses to low imminence threats
are qualitatively different than the high imminence threat behaviors that
characterize fear.

●      Responses to 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.

●       Frustrative non-reward: Reactions elicited in response to
withdrawal/prevention of reward, i.e., by the inability to obtain positive
rewards following repeated or sustained efforts.

●      Loss: A state of deprivation of a motivationally
significant con-specific, object, or situation. Loss may be social or nonsocial
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.

Positive Valence Systems

Systems primarily responsible for responses to positive motivational situations or contexts, such as reward seeking, consummatory behavior, and reward/habit learning.

●      Approach motivation: A multifaceted construct involving
mechanisms/processes that regulate the direction and maintenance of approach
behavior influenced by pre-existing tendencies, learning, memory, stimulus
characteristics, and deprivation states. Approach behavior can be directed
toward innate or acquired cues (i.e., unconditioned vs. learned stimuli),
implicit or explicit goals; it can consist of goal-directed or Pavlovian
conditioned responses. Component processes include reward valuation, effort
valuation/willingness to work, expectancy/reward prediction error, and action
selection/decision making.

●      Reward valuation: Processes by which the probability and
benefits of a prospective outcome are computed and calibrated by reference to
external information, social context (e.g., group input, counterfactual
comparisons), and/or prior experience. This calibration is influenced by
pre-existing biases, learning, memory, stimulus characteristics, and
deprivation states. Reward valuation may involve the assignment of incentive
salience to stimuli.

○      Effort valuation/Willingness to work: Processes by which the cost(s) of
obtaining an outcome is computed; tendency to overcome response costs to obtain
a reinforcer.

○      Expectancy/Reward prediction error: A state triggered by exposure to
internal or external stimuli, experiences or contexts that predict the
possibility of reward. Reward expectation can alter the experience of an
outcome and can influence the use of resources (e.g., cognitive resources).

○      Action selection/Preference-based decision making: Processes involving
an evaluation of costs/benefits and occurring in the context of multiple
potential choices being available for decision-making.

●      Initial responsiveness to reward attainment:
Mechanisms/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.

●      Sustained/Longer-term responsiveness to reward attainment:
Mechanisms/processes associated with the termination of reward seeking, e.g.,
satisfaction, satiation, regulation of consummatory behavior.

●      Reward Learning: A 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. Reward learning is a type of reinforcement
learning, and similar processes may be involved in learning related to negative
reinforcement.

●      Habit: Sequential, repetitive, motor, or cognitive
behaviors elicited by external or internal triggers that, once initiated, can
go to completion without constant conscious oversight. Habits can be adaptive by
freeing up cognitive resources. Habit formation is a frequent consequence of
reward learning, but its expression can become resistant to changes in outcome
value. Related behaviors could be pathological expression of a process that
under normal circumstances subserves adaptive goals.

Cognitive Systems

Systems responsible for various cognitive processes.

●      Attention: Attention refers to a range of processes that
regulate access to capacity-limited systems, such as awareness, higher
perceptual processes, and motor action. The concepts of capacity limitation and
competition are inherent to the concepts of selective and divided attention.

●      Perception: Perception refers to the process(es) 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.

●      Declarative Memory: Declarative memory is the acquisition
or encoding, storage and consolidation, and retrieval of representations of
facts and events. Declarative memory provides the critical substrate for
relational representations—i.e., for spatial, temporal, and other contextual
relations among items, contributing to representations of events (episodic
memory) and the integration and organization of factual knowledge (semantic
memory). These representations facilitate the inferential and flexible
extraction of new information from these relationships.
Language: Language is a system of shared symbolic representations of the world,
the self and abstract concepts that supports thought and communication.

●      Cognitive Control: A 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.

●      Working Memory: Working Memory is the active maintenance
and flexible updating of goal/task relevant information (items, goals,
strategies, etc.) in a form that has limited capacity and resists interference.
These representations: may involve flexible binding of representations; may be
characterized by the absence of external support for the internally maintained
representations; and are frequently temporary, though this may be due to
ongoing interference. It involves active maintenance, flexible updating,
limited capacity, and interference control.

Systems for Social Processes

Systems that mediate responses to interpersonal settings of various types, including perception and interpretation of others’ actions.

●      Affiliation and Attachment: Affiliation is engagement in
positive social interactions with other individuals. Attachment is selective
affiliation because 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. Affiliation
and Attachment require detection of and attention to social cues, as well as
social learning and memory associated with the formation of relationships.
Affiliation and Attachment include both the positive physiological consequences
of social interactions and the behavioral and physiological consequences of
disruptions to social relationships. Clinical manifestations of disruptions in
Affiliation and Attachment include social withdrawal, social indifference and
anhedonia, and over-attachment.

●      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. This construct is
reciprocal and interactive, and social communication abilities may appear very
early in life. Social communication is distinguishable from other cognitive
systems (e.g., perception, cognitive control, memory, attention) in that it
particularly involves interactions with conspecifics. The underlying neural
substrates of social communication evolved to support both automatic/reflexive
and volitional control, including the motivation and ability to engage in
social communication. Receptive aspects may be implicit or explicit; examples
include affect recognition, facial recognition, and characterization.
Productive aspects include eye contact, expressive reciprocation, and gaze
following. Although facial communication was set aside as a separate
sub-construct for the purposes of identifying matrix elements, social
communication typically utilizes information from several modalities, including
facial, vocal, gestural, postural, and olfactory processing.

○      Reception of Facial Communication: The capacity to perceive
someone’s emotional state non-verbally based on facial expressions.

○      Production of Facial Communication: The capacity to convey one’s
emotional state non-verbally via facial expression.
Reception of Non-Facial Communication: The capacity to perceive social and
emotional information based on modalities other than facial expression, including
non-verbal gestures, affective prosody, distress calling, cooing, etc.

○      Production of Non-Facial Communication: The capacity to express
social and emotional information based on modalities other than facial
expression, including non-verbal gestures, affective prosody, distress calling,
cooing, etc.

●      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/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. Perception
and Understanding of Self was organized into the following sub-constructs:

○      Agency: The ability to recognize one’s self as the agent of one’s
actions and thoughts, including the recognition of one’s own body/body parts.

○      Self-Knowledge: The ability to make judgments about one’s current
cognitive or emotional internal states, traits, and/or abilities.

●      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.

○       Animacy Perception: The ability to appropriately perceive
that another entity is an agent (i.e., has a face, interacts contingently, and
exhibits biological motion).

○       Action Perception: The ability to perceive the purpose of
an action being performed by an animate entity.

○       Understanding Mental States: The ability to make judgments and/or
attributions about the mental state of other animate entities that allows one
to predict or interpret their behaviors. Mental state refers to intentions,
beliefs, desires, and emotions.

Arousal/Regulatory Systems

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.

●      Arousal: Arousal is a continuum of sensitivity of the
organism to stimuli, both external and internal. Arousal: facilitates
interaction with the environment in a context-specific manner (e.g., under
conditions of threat, some stimuli must be ignored while sensitivity to and
responses to others is enhanced, as exemplified in the startle reflex), can be
evoked by either external/environmental stimuli or internal stimuli (e.g.,
emotions and cognition), can be modulated by the physical characteristics and
motivational significance of stimuli, varies along a continuum that can be quantified in any behavioral state,
including wakefulness and low-arousal states including sleep, anesthesia, and
coma, is distinct from motivation and valence but can covary with intensity of motivation
and valence, may be associated with increased or decreased locomotor activity,
and can be regulated by homeostatic drives (e.g., hunger, sleep, thirst, sex).

●      Circadian Rhythms: Circadian Rhythms are endogenous
self-sustaining oscillations that organize the timing of biological systems to
optimize physiology and behavior, and health. Circadian Rhythms: are
synchronized by recurring environmental cues; anticipate the external
environment; allow effective response to challenges and opportunities in the
physical and social environment; modulate homeostasis within the brain and
other (central/peripheral) systems, tissues and organs; are evident across
levels of organization including molecules, cells, circuits, systems,
organisms, and social systems.

●      Sleep and 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. Homeostatic and circadian processes regulate the
propensity for wakefulness and sleep. Sleep is: reversible, typically
characterized by postural recumbence, behavioral quiescence, and reduced
responsiveness; has a complex architecture with predictable cycling of NREM/REM
states or their developmental equivalents. NREM and REM sleep have distinct
neural substrates (circuitry, transmitters, modulators) and EEG oscillatory
properties intensity and duration is affected by homeostatic regulation; is
affected by experiences during wakefulness; is evident at cellular, circuit,
and system levels; has restorative and transformative effects that optimize
neurobehavioral functions during wakefulness.