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Table 3 Mapping of BeCOME assessments onto RDoC

From: The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes

RDoC DomainRDoC ConstructsGenesMole-culesCellsCircuitsaPhysiologyBehaviorSelf-ReportParadigms/Tasks
NegativeValenceAcute threat (“fear”)Genome- and systemwide OMICS assessments (blood draws):
- DNA, polygenic risk scores
- Epigenetic markers (e.g. DNA methylation, non-coding RNAs, histone modifications
- Gene expression
- Proteomics and Metabolomics
- Peripheral blood mononuclear cells (PBMC), induced pluripotent stem cells (IPSC)
- In vitro dexamethasone stimulation of cells
Autonomic nervous system, amygdala, hippocampus, central nucleus, dmPFC (pl), dorsal ACC, dPAG, hypothalamus, ICMs, insular cortex, latPFC/insula, LC, OFC, PAG, pons, rostral/vent ACCBlood pressure, heart rate, startle EMG, pupillometry, skin conductanceEstimation of the probability of aversive event (electrical shock), number of mistakes on mental arithmetic taskSymptomatic assessment of phobias (M-CID/DIAX)Fear conditioning and extinctionb, imaging stress testc
Potential threat (“anxiety”)Bed nucleus of stria terminalisPotentiated startle, average cortisol levels Intolerance of Uncertainty Scale, Behavioral Inhibition Scale (BIS), Body Sensation Questionnaire (BSQ), Agoraphobic Cognitions Questionnaire (ACQ)Startling noise presentationb
Sustained threatAttention/vigilance network, dysregulation of amygdala/cingulate reactivity, habit systems (Striatum/ caudate/accumbens), hypothalamic nuclei, PVTDysregulated HPA axisAnhedonia measures, decreased appetitive behavior (MADRS item No. 5), memory retrieval deficits (episodic memory task)Childhood trauma Questionnaire (CTQ), KIFTL = modified version of the early trauma inventory, section N of M-CIDI/DIAXEpisodic memory taskd
LossAmygdala, default mode network, dorsolateral prefrontal cortex, habit systems (Striatum/ caudate/ accumbens), hippocampus, insula, orbitofrontal/parietal cortex, posterior cingulate gyrus, PVN, reward circuitry, vmPFCANS, HPA axis, neuroimmune, prolonged psycho-physiological reactivity,Sadness (MADRS item No. 1)
Guilt (MADRS item No. 9), executive function, attentional bias to negative valenced information (identification of emotional face expression, response time)
Loss events questionnaire, Munich Event List 
Frustrative nonrewardAmygdala, hypothalamus, LC, OFC, PAC, parasympathetic system, septum, striatum Aggressive behaviors (can be derived from personality measures)  
Positive ValenceReward responsivenessAnterior insula, dorsal ACC, lateral hypothalamus. Medial OFC, nucleus accumbens, vental pallidum, ventromedial PFC, VTAPupillometry, heart rateResponse time, decision-making in social Bayes taskBehavioral inhibition system, Behavioral approach system (BIS/BAS)Reward anticipation taskc (= monetary incentive delay task), time estimation taskc (= simple guessing task)
Reward learningAmygdala, basal ganglia, dorsal ACC, lateral habenula, orbitofrontal cortex rostral medial tegmentum, substantia nigra/VTA, ventral striatumCortical slow waves, heart rate change, skin conductance  Probabilistic social reward learning task
Cognitive SystemsAttentionBasal forebrain limbic system, dorsal/ventral attention network Processing speed, number of mistakes d2-Rd, trail making testd
Declarative memoryHippocampal circuitry, PFC and PPC interactions with multiple association cortices Short and delayed recall Episodic memory taskd
Cognitive controlFrontopolar/anterior LPFC (BA10), Inhibition of DMN, dorsolateral prefrontal cortex, posterior parietal cortex, VLPFC Response time, sensitivity to interference, inhibition Stroopd
Working memoryDorsal parietal, dorsolateral prefrontal cortex, inferior parietal cortex, PFC-parietal-cingulate-dorsal thalamus-dorsal striatum, MD, VA thalamus, VLPFCPupillometry, heart rateNumber of mistakes Verbal N-backc, 2-backd
Arousal and Regulatory SystemsArousalBasal forebrain nuclei to cortical circuits, cholinergic and monoaminergic nuclei projections to thalamic and cortical, Cortical circuits such as fronto-insular and dorsal anterior cingulate etc.Heart rate, pupil size, blood pressure, pulse, reduced habituation in standard psychophysiological measures (startel respone, skin conductance), HPA axisStartle responseSubjective ratings during stress testImaging stress testc, Fear conditioning/extinctionb, resting state fMRI, Heart rate variability (mini-ECG), pupillometry, electrodermal activity
Circadian rhythms
 Pulse, heart rateCircadian rest/activity rhythms in the real world, motor behaviors during sleepSubjective daily sleep logs during actigraphyActigraphy, Mini-ECG, sleep-dependent memory consolidation (fear extinction)b
Social ProcessesAffiliation and attachmentAmygdala, BNST, FF gyrus, Nacc, OFC, PVN, VMPFCImmune markers, activation of sympathetic activity, HPA axis Attachment style (RSQ)
Social anhedonia (ACIPS)
Social communicationAmygdala Identification of emotionsSize of social network (SNQ)Emotional Faces Taskc
Perception and understanding of selfLeft inferior frontal cortex, posterior cingulate/precuneus, MPFC Evidence that one understands ownership of one’s own body parts or action (thoughts/behaviors), hallucinationsLocus of control (IE-4, attributional style questionnaire), psychotic section of M-CIDI 
Perception and understanding of othersMPFC, precuneus, superior temporal sulcus, temporal pole, TPJ  Emotional/autism quotient (EQ/AQ)Emotional Faces Taskc
  1. aas listed in the RDoC matrix; btask performed during psychophysiological measurements; ctask performed during imaging measurements; dtask performed during neuropsychological measurements