TABLE 3.

Similar-appearing items leading to diverging RDoC domain assignments

ITEM	COMMENTARY
Tension	The symptom of tension, IDS-SR Item 7, feeling anxious/tense, and PANSS Item G4, tension, appear similar. Yet, the IDS-SR Item 7, feeling anxious/tense, was assigned to NVS as primary and ARS as secondary domain. In contrast, PANSS Item G4, tension, was assigned to ARS as primary and NVS as secondary domain. This difference in assignment was due to the presence of “physical manifestations of fear, anxiety, and agitation, such as stiffness, tremor, profuse sweating, and restlessness” in the line item’s description of PANSS Item G4, tension, which was not present in the IDS-SR Item 7. Similar discrepancies in descriptions resulted in the MADRS Item 3, inner tension, being assigned to NVS/ARS (along with IDS-SR Item 7), whereas the HAM-A Item 2, tension, mapped onto ARS/NVS (along with PANSS Item G4) because their descriptions emphasized trembling and restlessness.
Sadness	The apparent sadness and reported sadness items in the MADRS and the depression item in the PANSS were also placed into different RDoC domains. While these would appear to be similar at face value, and the group placed these all primarily in the NVS domain, apparent sadness was placed secondarily in SP and the other items in PVS. Apparent sadness emphasized elements of the communicative aspect of sad affect, suggesting social processes were a component of the assessment for this item, compared to the other two items. For the PANSS item depression, the basis for rating is explicitly given as “verbal report of depressed mood during the interview and its observed influence on the patient’s attitude and behavior as reported from primary care workers or family.”
Psychomotor retardation	The HAM-D17 item retardation was allocated to the SS domain as primary due to its emphasis on motor speed and the CS domain as secondary due to its description of slowness of thought and speech and inability to concentrate. In addition, the description mentions stupor, which could potentially justify placing it into the ARS domain, as it is congruent with the element of coma, a low arousal state, though this level of retardation is rarely encountered. This observation demonstrates the challenge for some rating scale items for which extreme severity can result in changes in the apparent best matching RDoC domain.
Activity	The MADRS item lassitude and IDS-SR item leaden paralysis/physical energy both fit best with SS followed by ARS. Strong consistency was observed for the IDS-SR item feeling restless, the HAM-D17 item agitation, and the PANSS Item P4, excitement, all placed in ARS as for primary and SS domain secondarily. ARS was justified by the line items’ descriptions of locomotor activity. SS was not selected as primary because the descriptions do not contain elements of the motor action construct, such as action planning, sensorimotor dynamics, initiation, and execution.
Guilt	The HAM-D17 item feelings of guilt and the PANSS Item G3, guilt feelings, were placed in CS and SP. CS was selected as the primary domain because the items’ descriptions for the higher levels of severity contain elements of delusions, a form of cognitive distortion. SP was selected as the secondary domain because the item’s description contains elements of the perception and understanding of self construct. For PANSS Item G3, guilt feelings, SP was selected as the secondary domain because the item includes elements of communication, such as verbal report of guilt feelings and the influence of thoughts and attitudes on those feelings. Experts agreed that cognitive distortions would fall into the language construct of the CS domain, as it encompasses a system of shared symbolic representations of the world, the self, and abstract concepts that support thought and communication.
Insight	The HAM-D17 Item 17, insight, and the PANSS Item G12, lack of judgment and insight, were assigned to CS as primary and SP as secondary domain because the items’ descriptions contain elements from the perception and understanding of self construct within the SP domain.
Self-perception	The IDS-SR Item 16, view of myself, and Item 29, interpersonal sensitivity, were assigned to SP and NVS. SP was selected as the primary domain because the items’ descriptions contain elements from the perception and understanding of self construct, including judgments of self, such as self-awareness, self-monitoring, and self-knowledge. NVS was selected as the secondary domain because the item’s description contains elements of negative view of self and presence of self-blame, or the acute threat (fear) construct, including perceived threat, respectively.
Social withdrawal	The PANSS Item N4, passive/apathetic social withdrawal, and Item G16, active social avoidance, were assigned to SP as the primary domain because the items’ descriptions contain elements of diminished social interest and initiative and the effect that this has on interpersonal interactions. A second domain for this item was not selected because advisors agreed that it would vary depending on the observer (N4) or mechanisms associated with the underlying causes of the symptoms (G16). The basis for rating for PANSS Item N4 or Item G16 is explicitly given as “social behavior reports from primary care workers or family” only, thus not directly from the patient nor behaviors directly observed during the interview.
Thought disorder	PANSS Item G15, preoccupation, and PANSS Item P6, suspiciousness/persecution, were assigned to CS and SP. CS was selected as the primary domain because the items’ descriptions include elements of cognitive distortions. SP was selected as the secondary domain because the basis for rating the items is interpersonal behavior observed during the interview. Experts discussed the addition of NVS for PANSS Item P6, as an additional secondary domain because the item’s description contains mention of distrustful attitude, suspicious hypervigilance, and guardedness as outcomes of fear and sustained threat.

ARS: Arousal/regulatory systems; CS: Cognitive systems; HAM-A: Hamilton Anxiety Rating Scale; HAM-D17: 17-item Hamilton Depression Rating Scale; IDS-SR: Inventory of Depressive Symptomatology, Self-Report; MADRS: Montgomery-Asberg Depression Rating Scale; NVS: negative valence systems; PANSS: Positive and Negative Syndrome Scale; PVS: positive valence systems; RDoC: Research Domain Criteria; SP: social processes; SS: sensorimotor systems