The Research Domain Criteria (RDoC) project is an initiative of personalized medicine in psychiatry developed by US National Institute of Mental Health (NIMH). In contrast to the Diagnostic and Statistical Manual of Mental Disorders (DSM) maintained by the American Psychiatric Association (APA), RDoC aims to address the heterogeneity in the current nosology by providing a biologically-based, rather than symptom-based, framework for understanding mental disorders. "RDoC is an attempt to create a new kind of taxonomy for mental disorders by bringing the power of modern research approaches in genetics, neuroscience, and behavioral science to the problem of mental illness."

Call for creation

The National Institute of Mental Health oversees the RDoC initiative.

The 2008 NIMH Strategic Plan calls for NIMH to "Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures." The strategic plan continues:

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, affect 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.

Contrast with DSM

On April 29, 2013, a few weeks before the publication of the DSM-5, NIMH director Thomas Insel published a blog post critical of the DSM methodology and highlighting the improvement offered by the RDoC project.

Wrote Insel:

While DSM has been described as a 'Bible' for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been "reliability" – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure.

In that post, Insel wrote: "Patients with mental disorders deserve better." He would later elaborate on this point, saying "I look at the data and I'm concerned. ... I don't see a reduction in the rate of suicide or prevalence of mental illness or any measure of morbidity. I see it in other areas of medicine and I don't see it for mental illness. That was the basis for my comment that people with mental illness deserve better."

In their effort to resolve their issues with the new DSM, the NIMH launched the Research Domain Criteria Project (RDoC), based on four assumptions:

A diagnostic approach based on the biology as well as the symptoms must not be constrained by the current DSM categories, Mental disorders are biological disorders involving brain circuits that implicate specific domains of cognition, emotion, or behavior, Each level of analysis needs to be understood across a dimension of function, Mapping the cognitive, circuit, and genetic aspects of mental disorders will yield new and better targets for treatment.

Insel stressed that the RDoC is not designed as diagnostic criteria to replace the DSM, but rather as a research framework, for future development. His argument centers around the claim that, "symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment." As a result of this position, the NIMH is no longer using the DSM as the criteria upon which they will evaluate funding of future clinic trials.

DSM researcher Eric Hollander was quoted as saying "I do think it does represent a lack of interest and faith on behalf of NIMH for the DSM process and an investment in alternative diagnostic systems."

A NIMH description of RDoC explained:

Currently, diagnosis in mental disorders is based on clinical observation and patients' phenomenological symptom reports ... However, in antedating contemporary neuroscience research, the current diagnostic system is not informed by recent breakthroughs in genetics; and molecular, cellular and systems neuroscience.

RDoC matrix

The RDoC matrix is one way of organizing the concepts involved, with domains as tables, constructs as rows, sub-constructs as subrows and units of analysis often presented as columns.

Negative Valence Systems, as of January 2022
ConstructGenesMoleculesCellsCircuitsPhysiologyBehaviorSelf-reportsParadigms
Acute Threat (Fear)n/aBDNFCCKCortisol / CorticosteroneCRF familyDopamineEndogenous cannabinoidFGF2GABAGlutamateNeuropeptide SNeurosteroidNMDARNPYOXOxytocinSerotoninVasopressinGABAergic cellsGliaNeuronPyramidal cellAmg basal aCeN lateral medial ACC dorsal rostral ANS Hi posterior anterior Hy ICMs Ins OFC PAG dorsal ventral Pons LC PFC vmPFC (il) dmPFC (pl) LPFC/Ins RPVMBP EDA EMG facial Eye tracking Heart rate Pupillometry Breathing Response accuracy Startle context fear-potentiatedAnalgesia (reduced pain perception)Early developmental approachAvoidanceFacial expressionFreezingOpen fieldInhibitory controlResponse timeRisk assessmentSocial approachFear survey scheduleSUDSBehavioral approach testCO2 challenge testCold pressor testFear conditioningStranger testsTrier social stress test
Potential Threat (Anxiety)n/aCortisolCRF familyPituitary cellsBNSTACTHAverage cortisol levelsPotentiated startlen/aAnxiety Sensitivity IndexBISFear of Negative Evaluation ScaleIntolerance of Uncertainty ScaleLEDSNPU Threat Task
Sustained Threatn/aACTHCRFHPA axis hormonesHiMicrogliaprefrontalAttention network Dysregulation of Amg reactivity Dysregulation of cingulate reactivity Habit systems Striatum Caudate Accumbens Hy nuclei PVT Vigilance networkDysregulated HPA axisError-related negativityAnhedonia/decreased appetitive behaviorAnxious arousalAttentional bias to threatAvoidanceDecreased libidoHelplessness behaviorIncreased conflict detectionIncreased perseverative behaviorMemory retrieval deficitsPunishment sensitivityChildhood Trauma QuestionnaireLEDSRisky FamiliesSTRAINTESIYouth Life Stress Interviewn/a
Lossn/aAndrogenCRHEstrogenGlucocorticoid receptorInflammatory moleculesOxtADHn/aAmg Default mode network DLPFC Habit systems Striatum Caudate Accumbens Hi Ins OFC Parietal cortex PCC PVN Reward circuitry vmPFCANSHPAneuroimmuneProlonged psychophysiological reactivityAmotivationAnhedoniaAttentional bias to negative valenced informationCryingExecutive functionGuiltIncreased self-focusLoss of driveLoss-relevant recall biasMorbid thoughtsPsychomotor retardationRuminationSadnessShameWithdrawalWorryLEDSSTRAINSadness eliciting film clips
Frustrative Nonrewardn/aDopamineGABAGlutamateSerotoninSteroidsADHn/aAmgHyLCOFCPAGPNSSeptumStriatumn/aRelational and physical aggressionFrustrative Nonreward Responsiveness SubscaleQuestionnaire of Daily FrustrationsLab-TABPSAP
Positive Valence Systems, as of January 2022
Construct / SubconstructGenesMoleculesCellsCircuitsPhysiologyBehaviorSelf-reportsParadigms
Reward ResponsivenessReward Anticipationn/an/an/an/an/an/an/aMonetary incentive delay
Initial Response to Rewardn/aCREBEndocannabinoidsFosBGlutamateMu and delta opioidOrexinn/aAnterior InsDorsal ACCLHMedial OFCNucleus accumbensVentral pallidumVentromedial PFCVTAn/aTaste reactivityConsummatory subscale of TEPSPANAS (state version)Simple guessing task
Reward Satiationn/an/an/an/an/an/an/aFixed-ratio satiation schedule
Reward LearningProbabilistic and Reinforcement Learningn/an/an/an/an/an/an/aDrifting double banditClassical conditioningProbabilistic reward taskProbabilistic stimulus selection task
Reward Prediction Errorn/aDopamineSerotoninn/aAmgBGDorsal ACCLateral habenulaOFCRostral medial tegmentumSubstantia nigra/VTAVentral striatumCortical slow wavesHeart rate changeSkin conductanceGoal trackingPavlovian approachReward-related speedingSign trackingAffective forecastingASAM scaleEating Expectancy InventoryGeneralized reward and punishment expectancy scaleSelf-report of cravingTEPS anticipatory scaleDrifting Double BanditRutledge Passive Lottery Task
Habit - PVSn/aAcetylcholineCo-released neuromodular glutamateCREBDopamine and dopamine-related moleculesFosBDopaminergic neuronsmedium spiny neuronsSubstantia Nigradorsal striatumMedial Prefrontal CortexSN/VTAVentral striatumn/aCompulsive behaviorsRepetitive behaviorsStereotypic behaviorsAberrant behaviors checklistMeasures of repetitive behaviorsDevaluation taskHabit Learning TaskHabit Task
Reward ValuationReward (probability)n/an/an/an/an/an/an/aProbability Choice TaskWillingness to Pay Task
Delayn/an/an/an/an/an/an/aDelay discounting
Effortn/aAdenosineDopamineGABAn/aBasolateral amygdaladorsal ACCVentral pallidumVentral striatum (nACC)VTAn/an/aDrive subscale of the Behavioral Activation ScaleEEfRT task
Cognitive Systems, as of January 2022
Construct / SubconstructGenesMoleculesCellsCircuitsPhysiologyBehaviorSelf-reportsParadigms
Attentionn/aImplementation GABA Glutamate Control ACh Dopamine Glutamate Histamine SerotoninParvalbumin-positive interneuronsBalance between TPN vs DMN Implementation local circuit interactions pulvinar TRN Control Amg Ascending / descending information pathways Attentional systems Basal forebrain limbic system Dorsal network Ventral networkfMRI Sensory areas from peripheral to central Auditory ERP N1 N2 Neural oscillations P1 P300 Processing negativity Visual ERP N2pc Negativity (SN) Neural oscillations P300 Selection modulations of sensory ERP components Slow waves Peripheral physiology Heart rate deceleration Pupil dilationANT task distractibilityAttentional lapses vs sustained attentionDistractibilityObject/feature attentionPsychophysicsSpatial attentionAttentional blink and psychological refractory period paradigmBlocked channel-selection tasksDichotic listeningdistraction paradigms (capture)Dual-task paradigmsinter-modal selective attentionspatial and non-spatial cuing paradigmstime-series of response times to extract variability and frequency domain analysesvisual search
PerceptionVisualn/aACHCatecholaminesGABAGlutamateNMDAPeptidesSerotoninMagnocellular (non-linear gain control)Parvalbumin-positive interneuronsParvoPyramidal cellsSubcortical Koniocellular Magnocellular Parvocellular Cortical Cortico-cortical connections into supra- and infra-granular layers Dorsal/ventral streams Non-retinogeniculate SC SCN Local circuitry Lateral interactions Top-down interactions Implicated in contextual and association fields (responsible for the influence of spatial context on target processing)Adaptation/habituationBOLD activation of cortical regionsERP componentsNclOscillations (scalp EEG, LFP, and single/multi-unit recording)ssVEPtransient VEPDiscrimination, identification and localizationPerceptual learningPerceptual primingReadingStimulus detectionVisual acuityPerceptual anomalies of schizophrenia and depressionScheme 1: Stages of Vision Early Vision Local computations Retinotopic representations Intermediate Vision Nonlocal properties of images Transformations beyond retinotopic representations Late Vision Representations of external objects Scheme 2: Commonly Used Research Paradigms Backward masking Biological motion processing Bistability Coherent motion Contour integration/interpolation Contrast sensitivity Cross modality paradigms Emotion expression identification Face identification Figure ground Lateral facilitation Multistability Object perception Object recognition/perceptual closure/perceptual organization Parallel/serial search Reading Vernier discrimination Visual illusion susceptibility Other Schemes Action-Perception loops Re-entrant processing
Auditoryn/aAcetylcholineGABAGlutamateNMDASerotoninCochlear hair cellsCortical and limbic inhibitory interneuronsRibbon synapsesNodes in Circuit A1 Anterior insula Brainstem Cochlea Inferior colliculus MGN STG Circuits Corticofugal Dorsal/ventral streamsAdaptation/ habituationAuditory steady-state response (ASSR)fMRIIntracortical EEGMetabolic changesMismatch negativity (MMN)N1Neural oscillationsP3aP50startle and PPIPerceptual identificationPerceptual learningPerceptual primingSpatial localizationStimulus detectionAuditory hallucinationsHyperacusisAction-Perception loopsAuditory maskingauditory scene perception (e.g., streaming)BistabilityCategorizationCross-modal interactionsDetection of speech in noiseDeviance detectionGatinginhibitory controlManipulation of ISI and/or intensityMcGurk (multisensory)novelty/oddball detectionObject perceptionRegularity and change detectionsame-different tasksself-monitoringtone detection (e.g., JND tasks)Tone matching
Olfactory / Somatosensory / Multimodaln/an/an/an/an/an/an/aManipulation of ISI and/or intensitySmell identification
Declarative Memoryn/aCholinergicGlutamatergicNoradrenergicOpioidGliaGranule cellsInhibitory and excitatory interneuronsPyramidal cellsExtrinsic hippocampal circuitryIntrinsic hippocampal circuitryPFC and PPC interactions with multiple association corticesAMPA-related synaptic plasticityconjunction codesfrontal/temporal coordinated oscillationsLTP/LTDNMDA-related synaptic plasticityplace cell activitysubsequent memory effect (fMRI, ERP)up/down statesDiscriminationFamiliarityLearningRecallRecognitionCognitive Assessment Interviewacquired equivalencedelayed recalllist and story learningPaired associate learningtransitive inference
Languagen/an/an/aInferior frontal cortexInferior Parietal CortexInferior temporal cortexLateral superior and middle temporal corticesOverlap with memory, motor, sensory, and emotional circuitsanterior negativitiesN400P600/late positivitiesCoherent discourseCoherent sentencesProduction and comprehension of wordsCognitive Assessment InterviewLanguage Production Linguistic corpus-based analyses of language output Naming Language Comprehension Ability to answer questions about the content of sentences and discourse Ability to distinguish between coherent and incoherent sentences and discourse Detection and classification of semantic relationships between words Listening and reading times to critical words and regions in linguistic input Patterns of eye movements (in eye tracking paradigms) or motor movements (in mouse tracking paradigms) to critical words and regions in linguistic input Patterns of eye movements to non-verbal visual stimuli during spoken language comprehension (the visual world paradigm) Experimental Manipulations Manipulations of different types of coherence and cohesion between clauses in discourse Manipulations of different types of relationships between individual words in priming paradigms Manipulations of predictability and acceptability, at different levels of representation, in a linguistic input Manipulations of relationships between language and non-verbal behaviors
Cognitive Control1 of 2: Goal Selection; Updating, Representation, and Maintenancen/an/an/aFrontopolar/Anterior LPFC (BA10)Inhibition of DMNn/an/aBRIEF (Gioa)Badre tasksKoechlin paradigmTask switching
2 of 2: Goal Selection; Updating, Representation, and Maintenancen/aACHDopamineGABAGlutamateNorepinephrinePVPyramidal cellsDorsolateral Prefrontal CortexPosterior Parietal CortexThalamocorticalGamma synchronyPupilometryDistractibilityOff-task behaviorsBRIEF (Gioa)Cognitive Failures QuestionnaireSANS/SAPS/PANSSAX paradigmsCued stimulus-response reversal tasksTask switchingTower tasks
1 of 2: Response Selection; Inhibition / Suppressionn/aACHDopamineGABAGlutamateNorepinephrinePVPyramidal cellsDorsolateral Prefrontal CortexPosterior Parietal CortexVLPFCGammaThetaImpulsive behaviorsBRIEF (Gioa)SANS/SAPS/PANSSFlankerSimonStroop
2 of 2: Response Selection; Inhibition / Suppressionn/aAcetylcholineDopamineGABAGlutamateNorepinephrinePyramidal cellsBA6/8 (FEF)Posterior Parietal CortexPre-Supplementary Motor AreaVentrofronto-striatalAlphaPupilometryShort interval cortical inhibition (TMS)DistractibilityImpulsive behaviorsOff-task behaviorsADHD Rating Scale (Dupaul)ATQ/CBQ Effortful ControlBRIEF (Gioa)Conners impulsivity scaleAntisaccadeConflicting and contralateral motor response taskCountermandingGo/NogoMotor persistence paradigms (e.g. NEPSY statue task)Stimulus-Resp IncompatStop-Signal Reaction Time
Performance Monitoringn/aDopamineSerotoninn/aACC / pre-SMA InsulaERNN2N450Post-error or post-conflict adjustments in performanceYBOCS total scoreFlankerSimonStroop
Working MemoryActive Maintenancen/aD1DopamineGABAGlutamateNMDADistinct types of inhibitory neuronsPyramidal cellsInferior Parietal CortexPFC-parietal-cingulate-dorsal thalamus-dorsal striatumVLPFCDeltaGamma wavesTheta wavesn/an/aAX-CPT/DPXChange detection tasksComplex Span tasksdelayed match to non sampledelayed match to samplekeep track taskLetter memory/running memoryLetter Number SequencingN-backSelf-Ordered Pointingsequence encoding and reproductionSimple Span TasksSternberg Item Recognition
Flexible Updatingn/aD2DopamineGABAGlutamateMedium Spiny Neurons (basal ganglia)dorsal striatumDorsolateral Prefrontal CortexMDPFC-parietal-cingulate-dorsal thalamus-dorsal striatumVA thalamusDeltaGamma wavesTheta wavesn/an/aAX-CPT/DPXComplex Span taskskeep track taskLetter memory/running memoryLetter Number SequencingN-backSelf-Ordered PointingSternberg Item Recognition
Limited Capacityn/aD1D2DopamineGABAGlutamaten/aDorsal ParietalDorsolateral Prefrontal CortexInferior Parietal CortexMDPFC-parietal-cingulate-dorsal thalamus-dorsal striatumVA thalamusVLPFCDeltaGamma wavesTheta wavesn/an/aAX-CPT/DPXChange detection tasksComplex Span tasksdelayed match to non sampledelayed match to samplekeep track taskLetter memory/running memoryLetter Number SequencingN-backSelf-Ordered Pointingsequence encoding and reproductionSimple Span TasksSternberg Item Recognition
Interference Controln/aD1D2DopamineGABAGlutamateCalbindinCalretininDistinct types of inhibitory neuronsParvalbuminDLPFCPFC-parietal-cingulate-dorsal Th-dorsal striatumNeural waves Delta Gamma Thetan/an/aComplex Span tasksDelayed match to non-sampleDelayed match to sampleKeep track taskLetter memory/running memoryLetter number sequencingn-backSelf-Ordered PointingSimple Span TasksSternberg Item Recognition
Social Processes, as of January 2022
Construct / SubconstructGenesMoleculesCellsCircuitsPhysiologyBehaviorSelf-reportsParadigms
Affiliation and Attachmentn/a3CRFCRFR2D1DopamineKORMu opioid receptorOxytocinoxytocin receptorVasopressinvasopressin 1a receptorMagnocellular OTAmygdalaBNSTFF gyrusNAccOFCPVNVMPFCVTA- NAcc- VP-amygdalaactivation of sympathetic activityHPA axis activationHPA down-regulationImmune markersimmune responses (“sickness”)Sex steroid changesVagal tonevagal withdrawalAttachment Formation Maintaining proximity Preference for individual Attachment Maintenance Distress upon separationAdult Attachment InterviewAttachment Questionnaire for Children ScaleAttachment Style interviewBartholomew and ShaverBereavement scalesExperience in Close Relationships ScaleInventory of Parent and Peer Attachment ScaleMultidimensional Scale of Perceived Social SupportParental Bonding InstrumentQSORT Parent Attachment interviewSocial Anhedonia scaleSocial subscales of depressionCyberballOne-armed Bandit Task
Social CommunicationReception of Facial Communicationn/aDopamineFMRPGABAOxytocinSerotoninTestosteroneVasopressinFace selective neuronsMirror neuronsamygdala-brainstemIFG-INS-amygdala/VSOFC-ACC-amygdala-striatumResting state networksV1-FFA-STS-amygdalaV1-FFA-STS-VSECoG frontal brain asymmetryFacial EMGHR/BP/respirationLocal cerebral blood flow changesN170N250Network dynamicsPupil dilationSCRStartle reflexBehavioral observation/coding systemsEye gaze detectionIdentification of emotionImplicit mimicryScanning patternsArousal ratingsFace dimensional rating scalesGaze CuingPenn Emotion Recognition (ER-40)
Production of Facial Communicationn/aAPContactinn/aEye Movements PPC-SC-SNc-SEF-FEF-CB Facial Expression Regions including PAG, ACFacial EMGHR variabilityNIRSPhotoplethysmography (skin color measure of capillary dilation; temperature)Pupil dilationSCTear productionBehavioral observation/coding systemsEye gaze aversion/contactFacial affect productionHead turningImitation of facial gesturesJoint attentionReciprocal emotional expressionReciprocal eye contactBerkeley Expressivity Questionnairen/a
Reception of Non-Facial Communicationn/aOxytocinVasopressinn/aA1-RSTGMPFCSuperior Temporal SulcusVLPFCEEG features e.g., evoked gammaLocal cerebral blood flow changesNetwork dynamicsComprehension of emotional prosodyComprehension of non-verbal gesturesHumor comprehensionIrony/sarcasm comprehensionMetaphor comprehensionSocial Responsiveness ScaleMultimodal Social Paradigms
Production of Non-Facial Communicationn/an/an/aR-IFG-RSTGSongbird circuitsn/aCrying/laughingGestural/postural expressionsInteractive playResponse to distress/separation distressSpeech (affective) prosodyVocalizationsSocial Responsiveness ScaleMultimodal Social Paradigms
Perception and Understanding of SelfAgencyn/an/an/aRight insula-right inferior frontalRight parietalSMA-somatosensory-premotorScalp Motor PotentialsDelusions of controlEvidence that one understands ownership of one’s own body parts or action (thoughts/behaviors)HallucinationsStereotypic behaviorsPerceptual Aberration Scalen/a
Self-Knowledgen/an/aVon Economo neuronsleft inferior frontal cortexMPFCposterior cingulate/precuneusventral anterior cingulate (valence specific)P300s to self-relevant stimuliDevelopmentally appropriate perception of one’s competences, skills, abilities beliefs, intentions, desires, and/or emotional statesLevels of Emotional AwarenessPrivate Self-ConsciousnessSelf Components of Attributional Styles QuestionnaireSelf-monitoring scaleToronto Alexithymia scaleSelf-Referential Memory Paradigm
Perception and Understanding of OthersAnimacy Perceptionn/an/an/aextrastriate body areafusiform face areaoccipital face areaSuperior Temporal SulcusMU SuppressionAbility to appropriately attribute animacy to other agentsn/aPoint Light Displays of Biological Motion
Action Perceptionn/an/aMirror neuronsInferior Parietal CortexSuperior Temporal Sulcusventral/dorsal premotorcortico-spinal facilitation (TMS)MU SuppressionAbility to identify what actions an agent is executingGaze followingImitationMimicryBalanced Emotional Empathy ScaleEmpathy QuotientPerspective Taking and Empathic Concern subscales of the Interpersonal Reactivity IndexHow/Why Task
Understanding Mental Statesn/aOxytocinVasopressinn/aMPFCprecuneusSuperior Temporal Sulcustemporal poleTPJn/aDevelopmentally appropriate interpretations of other intentions, goals and beliefsBalanced Emotional Empathy ScaleEmpathy QuotientOther components of Attributional Styles QuestionnairesPerspective Taking and Empathic Concern subscales of the Interpersonal Reactivity IndexHinting TaskReading the Mind in the Eyes
Arousal and Regulatory Systems, as of January 2022
ConstructGenesMoleculesCellsCircuitsPhysiologyBehaviorSelf-reportsParadigms
Arousaln/aACh CRF Cytokine Dopamine GABA Ghrelin Glutamate Histamine OX Leptin NPY NE/NA Opioid Oxt Serotonin ADHBasal forebrain nuclei aCeN Dorsal raphe Hy LH perifornical dorsomedial LDT LC PPT TMN Ventral tegmental areaBasal nuclei to cortical circuits Cholinergic & monoaminergic nuclei / projections aCeN to monoaminergic and basal forebrain cholinergic nuclei brainstem projections to basal forebrain nuclei projections to Th and cortical projections to midbrain and Pn reciprocoal projection Circadian & sleep-related circuits modulate and are modulated by arousal Cortical circuits fronto-insular area 32 Hy to thalamic and cortical circuits Reciprocal Hy Reciprocal NTS-aCeNEEG EMG ERP fMRI Neural activity Sex-specific differences in arousal Autonomic BP Breathing EDA Heart rate Pupil size HPA axis ACTH CRF GlucocorticoidAffective state Agitation Cognition Emotional reactivity Blinking Motivated behavior Motor activity Sensory reactivity Startle WakingADACL POMS arousal subscale Self-assessment mannequinCardiac pre-ejection period EDA HRV Psychomotor vigilance task Pupillometry
Circadian Rhythmsn/aSerotonin Input Dopamine GABA Glutamate Melanopsin NPY PACAP SP SCN synchronizing & modulating agents ADH Calbindin cAMP cGMP NO Steroids VIP Output ADH Cortisol GABA Melatonin VIPFibroblast ipRGC Medium spiny neuron Pars tuberalis cells Pinealocyte Rods and cones SCN "clock" cellsInput Raphe to SCN projection retinal cell RHT retinogeniculate tract Output BL / Hi central extended Amg (aCeN/BNST) HPA axis neuroendocrine cell groups Hy OX projections PVN, DMH, subparaventricular zone, PVT SCN / PVN / SCG / pineal SNS / PNS Intrinsic to SCN SCN core/shell Seasonal SCN / PVN / SCG / pinealGene expression Neural activity NeurotransmitterDrive-regulated behavior Locomotor activity Masking Neurobehavioral function Sleep-rated and waking behavior Sleep-wakeDiary-based measures of daily regularity/rhythmicity (e.g., Social Rhythm Metric) Morningness–eveningness questionnaire Munich Chronotype Questionnaire Phase, diurnal preference, chronotype (e.g., Horne-Ostberg, CTQ) Sleepiness, alertness, well-being, moodDLMO (phase estimate) Longitudinal Actigraphy Genetic approaches genome-wide association study candidate gene epigenomics circadian genomics (temporal gene expression) mutagenesis gene targeting quantitative trait locus
Sleep-Wakefulnessn/aACh Adenosine CRF Cytokine Dopamine GABA Galanin Glutamate Histamine OX NE/NA NPY Serotonin ADHAH and basal forebrain Brainstem LC Raphe LDT/PPT VTA HACER Hy PHR (TMN) Th MD RtNREM sleep; forebrain basal forebrain and AH projections to arousal-promoting cell groups thalamocortical tract REM sleep; brainstem mesopontine nuclei Wakefulness Arousal and Circadian Rhythms circuits also subserve wakefulnessBrain metabolic activity Capacity for wakefulness under low stimulation EEG sleep spindle slow wave theta wave EMG EOG NREM sleep and REM sleep Physiologic measures of sleepiness, homeostatic sleep drive during waking Sex-specific sleep physiology Sleep hormones Sleep latency Temporal and topographic organization of... homeostatic sleep drive during sleep sleep dynamics WakefulnessIntermediate/admixed sleep-wake states Rest-activity patterns Sensory arousal threshold Sleep co-sleeping deprivation and satiation inertia motor behaviors sex-specific behavior timing and variability Sleep-dependent neurobehavioral functions WakefulnessAlertness Dream report Fatigue Insomnia severity index Sleep quality, restoration, quantity Sleep timing Sleep-modulated symptoms Sleepiness Specific sleep symptomsFinger tapping motor sequence task Latency to persistent sleep Multiple sleep latency testing Non-REM sleep EEG slow wave activity Sleep spindle Total sleep time Wake time after sleep onset
Sensorimotor Systems, as of January 2022
Construct / SubconstructGenesMoleculesCellsCircuitsPhysiologyBehaviorSelf-reportsParadigms
Motor ActionAction Planning and Selectionn/an/an/aParietal cortex inferior posterior Premotor cortex STS SMA propern/aApraxia conceptual ideational ideomotor limb-kineticn/aGo-before-you-know
Sensorimotor Dynamicsn/an/aGranule cellsPurkinje cellsBGCerebello-olivary-pontine complexCerebellumParietal cortexSomatosensory cortexSubstantia nigraThShort afferent inhibitionDyspraxiaHyposensitivityWeaknessn/aSensory Motor Adaptation Tasks
Initiationn/an/an/aBGDorsal cingulateSMA propern/aApathyCatatonic stuporNegative symptomsPsychomotor retardationStutteringLille Apathy Rating ScaleLibet's Temporal Judgement
Executionn/an/aAlpha motor neuronsBetz cellsPyramidal cellsEfferent and afferent spinal and peripheral pathwaysMotor cortexBereitschaftspotentialCorticospinal tract excitabilityHoffmann's reflexMovement-related cortical potentialsUse-dependent plasticityActivity levelEhlers–Danlos syndromesPsychomotor retardationn/aMotor evoked potential latency
Inhibition and Terminationn/aDopamineGABANE/NAIntracortical inhibitory interneuronsStriatal interneuronsACC BG Cerebellum DLPFC FEF IFG IPL Lateral premotor cortex Mid-CgG PCC SMA proper Pre-SMA SPLCortical inhibitionOscillatory rhythmsPrepulse inhibitionActivity level Automatic obedience Catatonia immobility rituals negativism Perseveration Stereotypy Tics Utilization behaviorn/aStop-signal reaction time
Agency and Ownershipn/an/aMirror neuronCerebellum Corpus callosum IPL Sensorimotor Th S1 SMA proper Pre-SMAEfference copyReadiness potentialAlien hand syndromeFunctional movement disorderNeglectPerception of external controlStereotypyTicn/an/a
Habit - Sensorimotorn/aDopamineGABAGlutamateSerotoninn/aPtASensorimotor-BGn/aCompulsive behaviorStereotypyRush video-based tic rating scaleYale Global Tic Severity Scale2-step task
Innate Motor Patternsn/an/an/aBrainstem Hy Motor cortex Occulomotor systemCorneal reflexDisinhibition of early motor reflexes Incontinent affect Startle Stereotypyn/an/a

The domains are tentative: "It is important to emphasize that these particular domains and constructs are simply starting points that are not definitive or set in concrete." Also, subconstructs have been added to some constructs. For example, Visual Perception, Auditory Perception, and Olfactory/Somatosensory/Multimodal perception as subconstructs of the Perception construct.

Methodology

The RDoC methodology distinguishes itself from traditional systems of diagnostic criteria.

Unlike conventional diagnostic systems (e.g. DSM) which use categorization, RDoC is a "dimensional system" — it relies on dimensions that "span the range from normal to abnormal."

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. Early data driven approaches to RDoC based continuous transdiagnostic psychiatric phenotypes predict clinical prognosis across diagnosis and have genetic correlates that in not only clinical populations.

Further reading

  • Aragona, Massimiliano (June 2014). (PDF). Dialogues in Philosophy, Mental and Neuro Sciences. 7 (1): 11–20.
  • Cuthbert, Bruce N. (March 2015). . Dialogues in Clinical Neuroscience. 17 (1): 89–97. doi:. PMC . PMID . Archived from the original on October 31, 2016.
  • Elvevag, Brita; Cohen, Alex S.; Wolters, Maria K.; Whalley, Heather C.; Gountouna, Viktoria-Eleni; Kuznetsova, Ksenia A.; Watson, Andrew R.; Nicodemus, Kristin K. (September 2016). . American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 171 (6): 904–19. doi:. PMC . PMID . Open access
  • Jayson, Sharon (12 May 2013). . USA Today.
  • Ledford, Heidi (10 May 2013). . Nature News. doi:. S2CID .
  • Morris, Sarah E.; Cuthbert, Bruce N. (March 2012). . Dialogues in Clinical Neuroscience. 14 (1): 29–37. doi:. PMC . PMID .

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