Orexin Antagonism for Suicide Risk: A Proof-of-Concept Clinical Trial

Implicit Association Tests ( IATs) use reaction time (RT) to capture automatic, implicit processes to gauge implicit self-identification with a construct of interest. Participants classify stimuli presented in the center of the screen into categories. The category labels are located on the left and right of the screen and participants classify stimuli by selecting keys corresponding to the left or right. RTs are measured as participants complete this task thereby gauging implicit mental associations. This study uses two variations of the IAT, a suicide-related IAT and a Escape-Me IAT to determine the extent to which participants associate suicide-related and escape-related constructs with the self.

The Buss-Perry Aggression Questionnaire is a 20-item self-report questionnaire assessing four dimensions of aggression: physical aggression, verbal aggression, anger, and hostility. Participants indicate how well each item describes them on a 5-point scale ranging from 1 (Not at all like me) to 5 (Very much like me).

The Overt Aggression Scale Modified (OAS-M) is a clinician-administered interview of aggressive behavior. Participants are asked about "outbursts of anger" (reactive aggression) in the past week. The OAS-M is strongly related to measures of anger and differentiates between participants with and without intermittent explosive disorder, supporting its validity as a measure of reactive aggression.

The Point Subtraction Aggression Paradigm (PSAP) is a laboratory-based assessment of reactive aggression in which participants play a competitive computer game against a fictional opponent to obtain points that coincide with a monetary reward. The PSAP can be administered virtually through Inquisit Web, a software designed to facilitate virtual research experiments.

The Barratt Impulsiveness Scale (BIS-11) is a 30-item self-report questionnaire assessing the personality/behavioral construct of impulsiveness. It includes six first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and three second-order factors (attentional, motor, and non-planning impulsiveness). Participants rate each item on a 4-point scale ranging from 1 (Rarely/Never) to 4 (Almost Always/Always). Total scores can range from 30 to 120.

The Beck Scale for Suicidal Ideation (BSSI) is a 21-item self-report questionnaire assessing suicidal thinking that helps identify individuals at risk. It also measures a broad spectrum of suicide-related attitudes and behaviors. The first five items are often used as the screener, where participants are directed to item 20 if they score 0 on these items. The overall score is computed by totaling up the scores on the first 19 items. Each item is rated from 0 to 2. Scores range from 0 to 38, with a higher score indicating a higher level of suicide ideation.

The Columbia Suicide Severity Rating Scale (C-SSRS) is a clinician-administered questionnaire assessing suicidal ideation and behavior with four subscales: ideation severity (five types of ideation of increasing severity), intensity of ideation (Frequency, Duration, Controllability, Deterrents, and Reasons for Ideation), suicidal behavior (4 types of suicidal behaviors - actual, interrupted, aborted attempts and preparatory behaviors - and the total number), and behavior lethality (For suicide attempts or non-suicidal self-injurious behavior).

The gradCPT task is a continuous performance task designed to measure sustained attention and response inhibition. It involves monitoring a continuous stream of natural scenes from two categories-cities and mountains-with a 9:1 ratio. Participants respond either to the frequent or rare category, yielding a response rate of either 90% or 10%. The task is associated with substantial and stable individual differences, with performance correlating significantly with network connectivity both during task performance and in resting states. The gradCPT task is an important new paradigm in attention research, providing insights into the neural network of sustained attention and the role of response inhibition in performance.

The Emotional Gradual Onset Continuous Performance Task (emogradCPT), is used to characterize the impact of emotional distractors (background images) on the ability to sustain attention during an emotionally neutral task (digit discrimination task). The emogradCPT consists of digits that gradually fade from one to the next every 800ms, with participants responding to most digits (90% of trials) and withholding responses to rare digits (10% of trials). The task is associated with substantial and stable individual differences, with performance correlating significantly with network connectivity both during task performance and in resting states. The emogradCPT task is an important new paradigm in attention research, providing insights into the neural network of sustained attention.

The Hamilton Depression Scale (HAM-D) is a clinician-administered 17-item questionnaire assessing the severity of depressive symptoms. Each item measures a depressive symptom (e.g., feelings of guilt, anxiety somatic). Items are rated on a 5-point (0 to 4) or 3-point (0 to 2) scale.

The Generalized Anxiety Disorder-7 (GAD-7) assesses anxiety symptom severity over the past two weeks with seven items rated from 0 (not at all) to 3 (nearly every day). An additional item assesses how difficult these symptoms have made functioning, which is rated from "not difficult at all" to "extremely difficult." Total scores use items 1-7 and range from 0 to 21. A score of 10 or greater represents a cut point for identifying cases of GAD, and cut points of 5, 10, and 15 could be interpreted as representing mild, moderate, and severe levels of anxiety.

The Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-report questionnaire assessing sleep quality in clinical populations. It has seven subcategories: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The PSQI has both Likert-type and open-ended questions. Scores for the ordinal questions range from 0 to 3, with higher scores indicating more acute sleep disturbances.

The Patient-rated Inventory of Side Effects (PRISE) is a 32-item self-report questionnaire assessing the presence and severity of side effects experienced by patients from a medication. Each item is rated on a 4-point scale (0 to 3). Items are summed for total scores, and higher scores indicate greater severity and impact of side effects.