Trial Outcomes & Findings for CBT+ for Depression (NCT NCT06001346)

379 potential participants were screened online (119 excluded); 260 potential participants went on to complete a phone screen (176 excluded or declined to participate), 84 of them completed an intake assessment (44 excluded), and 40 participants were randomized as an intention to treat sample.

CBT+ for Depression

Working Alliance Inventory-Short Revised (WAI) is a 12-item survey on experiences over a therapy session and connection with a therapist. It consists of three subscales: tasks, goals, and therapist-client bond. The total range of scores is from 12-84 with higher scores indicating a better therapeutic alliance.

The Behavioral Activation for Depression Scale (BADS) will be used to assess changes in behavioral activity. The scale is designed to be administered weekly to measure changes over the course of Behavioral Activation for depression. It consists of 25 questions that inquire about Activation, Avoidance/Rumination, Work/School Impairment, and Social Impairment. Each item is rated on a 7-point scale from 0 (Not at all) to 6 (Completely) with total scores ranging: 0-150 where higher scores indicate greater behavioral activation.

The GRID-HAM-D is a clinician-completed questionnaire that will be used to rate depressive symptom severity. The questionnaire is designed for adults and is used to rate the intensity and frequency of depressive symptoms by probing mood, feelings of guilt, suicidal ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. As recommended by the Depression Rating Scale Standardization Team, Clinical Interviewers will follow the Structured Interview Guide and use GRID scoring, in which dimensions of intensity and frequency of a symptom are rated independently for each item. Total scores are calculated from each question and range from 0 to 52, with higher scores indicated greater depressive symptom severity.

The Patient Health Questionnaire-9 (PHQ-9) is a 9-question self-report instrument used to assess presence and severity of depressive symptoms, with scores categorized 0-4, 5-9, 10-14, 15-19, and 20-27 as minimal, mild, moderate, moderately severe, and severe depression, respectively.

The SCID is a clinician-administered semi-structured interview guide for making diagnoses according to the diagnostic criteria published in the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5). It provides diagnoses for inclusion and exclusionary diagnoses. Results show number of participants who meet criteria for Major Depressive Disorder (i.e., 'checked') or no longer meet criteria (i.e., 'unchecked').

The DARS is a self-report measure that assesses state anhedonia across multiple domains. DARS is a 17-item survey on state anhedonia divided into four domains: hobbies, food/drink, social activities, and sensory experiences. Subjects must list two activities within each of these categories that they consider their favorite and then respond to questions regarding their interest in/enjoyment of those activities on a 5-point Likert scale from "Not at all" (0) to "Very much" (4), with total scores ranging from 0 to 68, with higher scores representing reduced anhedonia.

An anhedonia Visual Analog Scale \[VAS\] with 0 indicating 'No pleasure at all' and 100 indicating 'Greatest pleasure imaginable' will be used to measure anhedonia. The VAS will be used to provide a supplementary assessment of anhedonia.

Serum BDNF will be quantified from a standard blood draw. Blood samples collected during Visits 1, 4, and 8 will be allowed to clot for 30 minutes and then centrifuged for ten minutes at 5500 RPM and 4 ◦C. Following centrifugation, blood serum will be extracted with samples stored at -80 ◦C until BDNF analysis. Enzyme-linked immunosorbent assay (ELISA) kits will measure the concentration of total BDNF in the serum according to the manufacturer's instructions. Each blood sample will be run in duplicate and averaged.

Generalized Anxiety Disorder 7 (GAD-7) is a self-reported questionnaire for measuring generalized anxiety disorder. GAD-7 has seven items, which measure the severity of various signs of GAD according to reported response categories of: Not at all (0 points), Several days (1 point), More than half the days (2 points), and Nearly every day (3 points). A total score is calculated ranging from 0 to 21, with higher scores indicating more severe anxiety symptoms.

The ATQ is a 30-item instrument that measures the frequency of automatic negative statements about the self. Each item is rated on the frequency of an occurrence from "not at all" to "all the time". Total scores are the sum of all 30 items (ranging 30-150), with higher totals indicating a higher level of automatic negative self-statements.

Session Evaluation Questionnaire (SEQ) will be used to evaluate session effectiveness. This includes responses to twenty-one items in a 7-point bipolar adjective format questionnaire to assess how the client feels about each CBT session. The questionnaire assesses session depth, smoothness, positivity, and arousal. An overall score of the subscales will be used in this study (ranging 7-28). Higher scores indicate more favorable session evaluations.

Lyssn is an AI-powered assessment platform for recording and managing session files, and all clinical interviews and therapy sessions will be recorded on the Lyssn platform. Lyssn will process the audio files from therapy sessions to generate session-level data regarding collaboration and empathy as metrics related to the primary client ratings of working alliance, as well as generating CTRS fidelity metrics which will be used in the ongoing supervision and fidelity monitoring of all sessions.

The NCI consist of 6 questions pertaining to nature connectedness. Participants respond using a 7-point Likert scale, ranging from 1 (Strongly Disagree) to 7 (Strongly Agree), with higher scores indicating greater levels of nature connectedness.

Participants will place an activPAL on the midline of the thigh on either leg and wear the monitor during all waking hours, removing it only for water-based activities (e.g., swimming). For data to be valid, the monitor must have been worn for 20 hours on at least 4 days, including a minimum of 3 weekdays and 1 weekend day. Sleep time will be parsed out from each day's sitting/lying time automatically using PALanalysis. From these data, average minutes of sitting per day will be used to assess total sedentary time, minutes of stepping time with a cadence ≥75 and \<100 will be used to assess minutes of light-intensity physical activity and minutes of stepping time with a cadence ≥100 will be used to assess minutes of moderate to vigorous physical activity (MVPA).

The SF-36 assesses health-related quality of life. It consists of eight scaled scores (including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher the score the less disability (i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability).

The IPAQ is a physical activity questionnaire that inquires about average amounts of walking, moderate physical activity, vigorous physical activity, and sitting time per week.

The C-SSRS will be used to assess and monitor suicide ideation and behavior. The severity of the ideation subscale is rated on a 5-point ordinal scale: 1 = wish to be dead, 2 = nonspecific active suicidal thoughts, 3 = suicidal thoughts with methods, 4 =suicidal intent, and 5 = suicidal intent with plan. Suicide behaviors are rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal,self-injurious behavior.

Health history will be self-reported. In addition, participants will be asked to list their current medications.

Demographic characteristics including age, sex, race, education, marital status, occupational status, and household income will be recorded or measured to characterize the sample.

The ACES consists of 16 questions pertaining to the respondents' first 18 years of life. Participants respond with yes or no regarding if a childhood adverse event occurred. Adverse events questions are grouped by categories. Participants are scored for each event category they are exposed to with scores ranging from 0 (unexposed) to 7 (exposed to all categories).