Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression (ENSURE; R21 MH130870)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 276
- 试验地点
- 4
- 主要终点
- Emotion Processing Domain: Emotional Recognition Task-Eyes
研究概览
简要总结
This is a cross-sectional pilot study designed to establish hot and cold cognitive functions and underlying neurocircuitry in older adults with MDD. The investigators will study 120 participants aged 21-80 years old with MDD. All participants will undergo clinical and neurocognitive assessment, and Magnetoencephalography (MEG)/Magnetic resonance imaging (MRI) procedures at one time point. The investigators will also enroll 120 demographically matched comparable, never-depressed healthy participants (controls) to establish cognitive benchmarks. Healthy controls will complete clinical and neurocognitive measures at one time point. To attain a balanced sample of adults across the lifespan, the investigators will enroll participants such that each age epoch (e.g., 21-30, 31-40, etc.) has a total of ten subjects (n=10) in both the healthy control cohort and depressed cohort.
详细描述
Major depressive disorder (MDD) is a common, chronic, and disabling disorder that affects individuals across the lifespan. Research has consistently found that a core domain of MDD is cognitive dysfunction, with the majority of clinical research focusing on cold cognitive functions such as attention, memory, and executive function. However, emotional "hot" cognitive impairments are also frequently observed in domains such as emotion processing, impulsivity, reward processing, and social cognition, and as with cold cognitive processes, have been implicated in both disease course and treatment outcomes.
The nomenclature of "cold" and "hot" cognitive function has been used to differentiate between those functions that are less influenced by emotional stimuli and/or processes (i.e., "cold" cognitive function) and those that have an emotional component and/or influence (i.e., "hot" cognitive function). The delineation of cold and hot cognitive function has critical implications for new mechanistic explanations and targeted antidepressant treatment development. Other researchers have proposed a testable cognitive neuropsychological model of MDD that describes the interaction of both cold and hot cognitive functions, underlying neurocircuitry, and proposed associated treatments.
Despite ample evidence of impairments associated with hot cognitive processes, behaviors, and associated neural circuity, there is significantly limited information regarding hot cognitive function in adults across the lifespan with MDD. Prior research has been limited by 1) measurement of only one or two hot cognitive functions, 2) no integration of cold and hot cognitive function assessment, and 3) sparse information on hot cognition and associated neurocircuitry in adults over the age of 60. Given the importance of cognitive dysfunction and aging on disease course and overall functioning in MDD, it is critical to identify mechanisms of action and targeted treatment approaches that will improve cognition to achieve the ultimate goal of improving overall disease course, functioning, and quality of life. Identification of brain network alterations associated with particular hot cognitive functions and treatments that modify these regions will move us closer toward personalized medicine and improved patient outcomes. A first critical step in this endeavor is to better characterize hot cognitive dysfunctions in MDD, their relationship to cold cognitive dysfunctions, potential effects of age on these dysfunctions, and information on the associated underlying neurocircuitry in older adults.
In the proposed preliminary study, 120 adults across the lifespan with MDD will complete clinical and cognitive measures, and MEG at one time-point. The investigators will also enroll 120 demographically matched comparable never-depressed healthy controls to establish cognitive benchmarks. The investigators will use existing healthy control data to establish resting-state and task-based MEG benchmarks. The study aims are:
Aim 1. Establish and integrate hot and cold cognitive dysfunction in adults across the lifespan.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants
- •Age between 21-80 years old
- •DSM-5 diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- •Inventory of Depressive Symptomatology-Clinician Rated version (IDS-C) total score > 14
- •Able to read, write, and comprehend English
- •Provide informed consent; willing to comply with study protocol
排除标准
- •History of bipolar disorder, schizophrenia, or schizoaffective disorder
- •Presence of psychotic features
- •Lifetime central nervous system (CNS) disease (including head injury with loss of consciousness > 5 minutes)
- •History of neurodevelopmental disorder (e.g., Autism spectrum disorder)
- •History of medical conditions that can affect neurocognitive function as well as be confounded with age (e.g., thyroid disease, endocrine illnesses)
- •Women who are pregnant
- •Current use of medications with known impacts on neurocognitive function (e.g., acetylcholinesterase inhibitors, amphetamine, methylphenidate, vortioxetine, sedatives)
- •Alcohol/substance use disorder within past 3 months
- •DSM-5 diagnosis of major cognitive impairment
- •Current sensory or physical impairment that interferes with testing.
- •Contraindication to MRI and MEG (only for depressed participants) (e.g., any electronic / metallic implants near or within the head or body, claustrophobia)
研究组 & 干预措施
Healthy Volunteer Participants:
- Male and female subjects
- Age between 21-80 years old
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol
干预措施: four self-report forms per the requirement of the NIH Common Data Elements project (Behavioral)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: Hot Cognitive Task (Behavioral)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: Cold cognitive tasks (Behavioral)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: Structural magnetic resonance imaging (sMRI) (Other)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: Magnetoencephalography imaging (MEG) (Other)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: four self-report forms per the requirement of the NIH Common Data Elements project (Behavioral)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: Four self-report measures to assess interpersonal functioning (Behavioral)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: Clinical assessments (Behavioral)
Major Depressive Disorder (MDD) Participants:
- Male and female subjects
- Age between 21-80 years old
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
- Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol.
Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
干预措施: ATHF (Other)
Healthy Volunteer Participants:
- Male and female subjects
- Age between 21-80 years old
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol
干预措施: Four self-report measures to assess interpersonal functioning (Behavioral)
Healthy Volunteer Participants:
- Male and female subjects
- Age between 21-80 years old
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol
干预措施: Hot Cognitive Task (Behavioral)
Healthy Volunteer Participants:
- Male and female subjects
- Age between 21-80 years old
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol
干预措施: Cold cognitive tasks (Behavioral)
Healthy Volunteer Participants:
- Male and female subjects
- Age between 21-80 years old
- Able to read, write, and comprehend English
- Provide informed consent; willing to comply with study protocol
干预措施: Clinical assessments (Behavioral)
结局指标
主要结局
Emotion Processing Domain: Emotional Recognition Task-Eyes
时间窗: baseline visit, total time= 12 minutes
Assesses accuracy and affective bias of emotional recognition. Participants identify emotion(e.g., happy, sad) based on 250ms presentation of eyes only. Hit rate (i.e., correct identification of each emotion).
Emotion Processing Domain: Face Affective Go No-Go
时间窗: baseline visit, total time= 6 minutes
Assesses affective bias associated with emotional faces. Participant must identify the target facial emotion (e.g., happy, sad), while ignoring other emotions. Discrimination accuracy (d-prime score for each emotion).
Emotion Processing Domain: Emotional Intensity Morphing Task
时间窗: baseline visit, total time= 5 minutes
Assesses the point of intensity for fascial emotion recognition. Faces are presented with slowly morphing emotional expressions (e.g., happy, sad, angry) that increases (point of detection) or decrease (emotion no longer perceived). Intensity threshold for each emotion and each condition (i.e., increases and decrease).
Impulsivity: Discounting Task
时间窗: baseline visit, total time= 7 minutes
Assesses rate of discounting across 5 levels of delay and 5 of probability. Participants decide between a standard fixed amount vs an immediately available alternative. Indifference points for each length of delay/degree of uncertainly, noted by area under the curve.
Reward Processing and Learning: Adapted Cambridge Gambling Task
时间窗: baseline visit, total time= 10 minutes
Assesses value-based choice. Participants bet on expected outcomes when presented with a colored (orange, purple) roulette wheel with the proportions of each color indicating 1 of 5 levels of certain/uncertain outcomes in the context of win or loss conditions. Risk Adjustment scores based on level of probability of win or loss.
Reward Processing and Learning: Reinforcement Learning Task
时间窗: baseline visit, total time= 10 minutes
Assesses reward and punishment learning. Participants are shown colored circles and choose the one they believe is more likely to win money. There are two conditions (no lose and no win). Learning rate (alpha) based on how fast participant learns new information (both win and loss). Risk Adjustment scores based on level of probability of win or loss.
Social Cognition: Moral Emotions Task
时间窗: baseline visit, total time= 13 minutes
Assesses moral judgment/emotional reactions to social situations. Cartoons depict characters intentionally or unintentionally harming one another. Participants rate feelings (e.g., guilt, shame) as either the victim or antagonizer in the scenario. Average ratings of guilt and shame in each scenario (victim or antagonizer).
次要结局
- Montreal Cognitive Assessment (MoCA): Cold Cognitive Function Testing.(Day 1/baseline)
- Delis-Kaplan Executive Function System (D-KEF)-Verbal Fluency Performance: Cold Cognitive Function Testing(Day 1)
- Everyday Cognition (ECog): Cold Cognitive Function Testing(Day 1)
- Delis-Kaplan Executive Function System (DKEF)-Color-Word Interference: Cold Cognitive Function Testing(Day 1)
- California Verbal Learning Test-3 (CVLT-3): Cold Cognitive Function Testing(Day 1)
- Delis-Kaplan Executive Function System (DKEF)-Tower Test: Cold Cognitive Function Testing(Day 1)
- Test of Premorbid Function (TOPF): Cold Cognitive Function Testing(Day 1)
- MEG: Magnetoencephalography(Baseline Day1)
研究者
Shawn McClintock
Professor
University of Texas Southwestern Medical Center