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Mechanisms of Depression and Anhedonia in Adolescents: Linking Sleep to Reward- and Stress-Related Brain Function (MoDA)

Primary Purpose

Depression in Adolescence

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Sleep extension and advance

Regular sleep duration and timing

About this trial

This is an interventional basic science trial for Depression in Adolescence

Eligibility Criteria

14 Years - 19 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 14-19 years of age Currently in high school Short and late sleep (weekday sleep duration ≤ 6 h & midpoint ≥ 4 am; n=100) or long and early sleep (weekday sleep duration ≥ 8h & midpoint ≤ 2:30 am; n=50), indexed by the Munich Chronotype Questionnaire Lifetime stressful event frequency greater than 4 on the Stress and Adversity Inventory (STRAIN) Screener Depressive symptom severity t-score greater than or equal to 45 on the Patient Reported Outcomes (PROMIS) Depression scale English language fluency Exclusion Criteria: High risk of DSM-IV alcohol dependence [past-year mean days of alcohol use per month at ages 18-19, 17, 16, and 14-15 of ≥4, ≥2, ≥1, and ≥0.5, respectively (9)], determined with the Timeline Follow-Back (TLFB); Past-year mean days of cannabis/nicotine use per month at ages 18-19, 17, 16, and 14-15 of ≥12, ≥6, ≥3, and ≥1.5, respectively, determined by the TLFB; Any repeated use of other substances (past-year use >1) determined by the TLFB; DSM-5 criteria for current or past severe alcohol/substance use disorder (≥6 symptoms), determined by the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 Present and Lifetime (K-SADS-PL); Acute alcohol intoxication, operationalized as a blood alcohol concentration of .02 or higher during Breathalyzer saliva screen; Current sleep disorders other than insomnia and delayed sleep phase determined by the Structured Clinical Interview for DSM-5 Sleep Disorders; Lifetime bipolar or psychotic disorder determined by the K-SADS-PL; Moderate to high suicide risk determined with the Columbia Protocol and Suicide Severity Rating Scale; Certain medical conditions (e.g., neurological disorder, heart failure or trouble, high blood pressure, history of unconsciousness > 5 minutes); Conditions that are contraindicated for fMRI (e.g., ferrous metal in the body); Photosensitizing medications that are contraindicated during the manipulation condition when bright light is administered (e.g., psychiatric neuroleptic drugs [e.g., phenothiazine], psoralen drugs, antiarrhythmic drugs [e.g., amiodarone], antimalarial and antirheumatic drugs, porphyrin drugs used in photodynamic treatment of skin diseases) travel across two or more time zones within the month prior to the overnight study visits. Beginning/ending a prescribed medication within 2 months of the observational study; Medication dose changes within the timeframe calculated as 5x the drug's half-life [the time to reach pharmacokinetic steady-state] before the initiation of the observational or experimental studies; Participant-anticipated changes in prescribed medications or medication dosing during the observational or experimental studies; Self-reported use of opioids, benzodiazepines, hallucinogens, or stimulants (other than caffeine and nicotine) within 24 hours of study visits; Self-reported symptoms of withdrawal from depressants or stimulants on days of study visits; Use of melatonin if participant is not willing to discontinue use for the duration of the study If possible, participants who are excluded for positive breathalyzer screen, self-reported substance use within 24 hours of study visits, or symptoms of withdrawal during study visits will be rescheduled for an alternative overnight visit within 2-3 days. Participants who are excluded for moderate to high suicide risk, recent or anticipated changes in medications, or travel across time-zones will become eligible for the study when they no longer meet these exclusion criteria.

Sites / Locations

University of OregonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sleep extension and advance "Lark Routine"

Regular sleep duration and timing "Owl Routine"

Arm Description

Participants go to bed 90 minutes earlier than their typical average bedtime to extend sleep duration and advance sleep timing

Participants go to bed at their typical average bedtime

Outcomes

Primary Outcome Measures

Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Depression Scale - Short Form (8-item)

The Patient-Reported Outcomes Measurement Information System (PROMIS) scale for Depression (8-item short form) will be administered at baseline, after each 2-week interval of intensive monitoring, and at follow-up, in reference to the past 7 days. The measure uses 5-point Likert scales, with scores ranging from 8 to 40 and higher scores indicating higher depression and lower scores indicating better outcome. Raw scores are converted to standardized T-scores using conversion tables published on the PROMIS website (nihpromis.org). T-scores of 50 represent the mean of the standardized sample.

Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Positive Affect Scale - Short Form (8-item)

The Patient-Reported Outcomes Measurement Information System (PROMIS)scale for Positive Affect (8-item short form) will be administered at baseline, after each 2-week interval of intensive monitoring, and at follow-up, in reference to the past 7 days. The measure uses 5-point Likert scales, with scores ranging from 8 to 40 and higher scores indicating higher positive affect and better outcome. Raw scores are converted to standardized T-scores using conversion tables published on the PROMIS website (nihpromis.org). T-scores of 50 represent the mean of the standardized sample.

Dimensional Anhedonia Rating Scale (DARS)

The Dimensional Anhedonia Rating Scale (DARS) will be used to assess state anhedonia related to 4 domains: hobbies, food/drink, social activities, and sensory experience. The 17-item measure assesses hedonic experiences "right now" using 4-point Likert scales. The DARS has high reliability and good convergent and divergent validity. The DARS scores range from 0 to 68, with higher scores indicating lower anhedonia and better outcome.

Reward-related brain function

fMRI during the Monetary Incentive Delay (MID) task will be used to measure BOLD regional response and functional connectivity related to anticipation and receipt of monetary rewards. This task reliably elicits activation in neural reward circuitry and is sensitive to depression and sleep/circadian factors.

Stress-related brain function

Stress-related brain function will be indexed using autonomic and neuroendocrine measures taken before and during the Trier Social Stress Task (TSST). The TSST is a lab-based social-evaluative threat task that reliably elicits subjective stress and increases in the stress-hormone cortisol.

Secondary Outcome Measures

Full Information

NCT ID

NCT05691439

First Posted

September 7, 2022

Last Updated

April 11, 2023

Sponsor

University of Oregon

Collaborators

Oregon Research Institute, University of Pittsburgh, National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT05691439

Brief Title

Mechanisms of Depression and Anhedonia in Adolescents: Linking Sleep to Reward- and Stress-Related Brain Function

Acronym

MoDA

Official Title

Mechanisms of Depression and Anhedonia in Adolescents: Linking Sleep Duration and Timing to Reward- and Stress-Related Brain Function

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 27, 2023 (Actual)

Primary Completion Date

December 31, 2026 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Oregon

Collaborators

Oregon Research Institute, University of Pittsburgh, National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This research will use biobehavioral approaches to generate understanding about the linkages between sleep duration and timing, stressful life events, and depressive symptoms in adolescents, with a long-term aim of developing effective preventative interventions.

Detailed Description

The last decade witnessed a steady growth from 8% to 14% in the prevalence of adolescents suffering from major depressive episode within the past year, and depression is expected to be the leading cause of global disability by 2030. The increase in depression incidence and disability is also related to increases in suicidality in adolescents, and the depressive symptom of anhedonia predicts suicidality above and beyond depression diagnosis. The high degree of morbidity and mortality associated with depression and anhedonia in adolescence makes this a key developmental period for research and intervention. Risk for depression and anhedonia is elevated in adolescents with insufficient sleep duration, late sleep timing, or elevated exposure to stressors. Alarmingly, only 30% of adolescents regularly obtain the recommended hours of sleep, and sleep timing is at its latest during mid- to late-adolescence. Adolescents also report high levels of stress related to work- and time-demands, and most will experience at least one major adverse life event before adulthood. Short/late sleep and stressors may also cause disruptions in reward- and stress-related brain function (e.g., medial prefrontal cortex response to monetary reward, autonomic and endocrine function during stressors), which are key biobehavioral mechanisms of depression and anhedonia. Short/late sleep habits are prime targets for depression intervention in adolescents; however, there is insufficient causal evidence that improving sleep opportunity and/or timing will alter the biobehavioral mechanisms of depression. The overall objective of this R01 is to evaluate a biobehavioral model whereby sufficient sleep duration and/or early sleep timing can reduce depressive symptoms and anhedonia by promoting reward- and stress-related brain function in adolescents. The long-term goal of this research is to leverage sleep and circadian function to promote mental health. A series of studies by the PI and Co-Is indicate that short sleep, late sleep, and stressful life events independently predict reward- and stress-related brain function and depressive symptoms in adolescents. However, these studies do not evaluate the interactive effects of sleep/circadian function and stressful life events, or use experimental designs. More recent research by the PI and Co-Is uses sleep-circadian manipulation to target reward- and stress-related brain function and improve mental health in adolescents. Building from this research, this R01 will test the central hypothesis that extending and/or advancing sleep will alter reward- and stress-related brain function, and decrease depressive symptoms and anhedonia, in adolescents with short and late sleep. This proposal is consistent with the NIMH Strategic Objective to identify clinically meaningful biomarkers and behavioral indicators of mental health.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depression in Adolescence

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sleep extension and advance "Lark Routine"

Arm Type

Experimental

Arm Description

Participants go to bed 90 minutes earlier than their typical average bedtime to extend sleep duration and advance sleep timing

Arm Title

Regular sleep duration and timing "Owl Routine"

Arm Type

Active Comparator

Arm Description

Participants go to bed at their typical average bedtime

Intervention Type

Behavioral

Intervention Name(s)

Sleep extension and advance

Other Intervention Name(s)

Lark routine

Intervention Description

Participants in the sleep extension and advance condition will maintain a stable sleep schedule that extends sleep duration and advances bedtime by 90 min relative to weekday bedtime. This chronotherapeutic manipulation will include blocking phase-delaying light in the evening using goggles with orange lenses ("blue blockers") beginning 2 h prior to bedtime, and 30 min of 506 lux blue-green light exposure in the morning beginning at rise time using bright light goggles (ReTimer Pty Ltd., Australia). Schedule and chronotherapy adherence will be reinforced using motivational techniques (e.g., securing motivation, preplanning, problem-solving), requiring participants to text the study coordinator and complete morning assessments at rise time, and monetary incentives.

Intervention Type

Behavioral

Intervention Name(s)

Regular sleep duration and timing

Other Intervention Name(s)

Owl routine

Intervention Description

Participants in the regular sleep duration and timing condition will keep a stable sleep schedule that matches their typical weekday sleep opportunity and timing. Schedule adherence will be reinforced using motivational techniques (e.g., securing motivation, preplanning, problem-solving), requiring participants to text the study coordinator and complete morning assessments at rise time, and monetary incentives.

Primary Outcome Measure Information:

Title

Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Depression Scale - Short Form (8-item)

Description

Time Frame

2 months

Title

Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Positive Affect Scale - Short Form (8-item)

Description

Time Frame

2 months

Title

Dimensional Anhedonia Rating Scale (DARS)

Description

Time Frame

2 months

Title

Reward-related brain function

Description

Time Frame

2 weeks

Title

Stress-related brain function

Description

Time Frame

2 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amy Konyn, PhD

Phone

541-346-0392

akonyn@uoregon.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melynda D Casement, PhD

Organizational Affiliation

University of Oregon

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Oregon

City

Eugene

State/Province

Oregon

ZIP/Postal Code

97403

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Melynda D Casement

Phone

541-346-7051

casement@uoregon.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data will be shared through publication of findings in scientific publications, and through investigator responses to direct data requests from members of the scientific community. We will make available to the research community any resource that is presented in a publication that is published or accepted for publication. We agree to release and share data in a timely manner. Should any intellectual property arise that may be patentable, the University of Oregon will ensure that the related technology (materials and final research data) remains widely available in timely fashion to the research community in compliance with policies and regulations governing research awards from the NIH. Participant data shared outside of the University of Oregon will be free of identifying information that would permit linkages to individual research participants and variables that could lead to deductive disclosure of the identity of individual subjects.

IPD Sharing Time Frame

We will make available to the research community any resource that is presented in a publication that is published or accepted for publication. We agree to release and share data in a timely manner, but no later than one year following completion of the funded project period or the date of publication of the main findings from our final data set.

IPD Sharing Access Criteria

In order to gain access to data, researchers who were not part of the original research protocol as defined by the University of Oregon IRB application must submit a detailed description of their project to the Investigator Committee. The proposal must include the investigator's personal identification and institutional affiliation, a current CV, qualifications, estimated duration of the proposed research, source of financial support, and a conflict of interest statement. The protocol described must include study aims, background and significance, and methods and types of analysis, and a description of the data requested and list of variables. Once approved, the investigator must complete the necessary University of Oregon IRB exempt research application form and document completion of a responsible conduct of research program. Data will not be provided that could identify individual research participants or that the original consent form expressly forbade.

Learn more about this trial

Mechanisms of Depression and Anhedonia in Adolescents: Linking Sleep to Reward- and Stress-Related Brain Function

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