Major Depressive Disorder (MDD)ENSURENCT05966532
Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression
An observational study of Major Depressive Disorder (MDD) and Healthy Adult Volunteer, run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder (MDD), Healthy Adult Volunteer
- What is being tested?
- Hot Cognitive Task, Cold cognitive tasks and Structural magnetic resonance imaging (sMRI)
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 276 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Dec 2023to 31 Aug 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Investigators will study 120 participants aged 21-80 years old with major depressive disorder (MDD). Participants with MDD will undergo clinical and neurocognitive assessment, and MEG/MRI procedures at one time point. Investigators team 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, research teams 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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Texas Arlington
Arlington, Texas, 76010
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-9127
About this study
Official title: Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression (ENSURE; R21 MH130870)
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.
Read the detailed description
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.
H1.1. Adults with MDD compared to healthy controls will have significantly greater hot and cold cognitive dysfunction as measured by a Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition (EMOTICOM) and the California Verbal Learning Test - Third Edition (CVLT-3)/Delis-Kaplan Executive Function System (D-KEFS), respectively.
H1.2. Age will be associated with greater hot and cold cognitive dysfunction.
Aim 2. Establish and compare specific brain networks underlying hot and cold cognitive tasks.
H2.1. EMOTICOM Emotion Recognition and Categorization task scores will be associated with resting-state and task-based MEG connectivity metrics in the salience network,
- Being tested
- Hot Cognitive Task, Cold cognitive tasks, Structural magnetic resonance imaging (sMRI), Magnetoencephalography imaging (MEG), four self-report forms per the requirement of the NIH Common Data Elements project
- Keywords
- Emotional Cognition
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hot Cognitive TaskBehavioural
- Emotion processing:
- Participants will be shown a series of faces that appear quickly and be asked to identify what emotion is shown.
- Participants will be shown a face of an emotion and indicate if participant can see the emotion changing.
- Participant will be shown a series of emotions and asked to respond to only a specific emotion.
- Motivation reward and processing:
- Participant will play with a simulated roulette and make a bet to evaluate their decision-making behavior.
- Participant will be shown colored circles and choose the one more likely to win money.
- Impulsivity:
- Participant will be shown a series of stimuli where they will be asked to respond to the correct stimulus.
- Social cognition:
- Participant will be shown a series of moral situations in which a character is accidentally or intentionally harmed and be asked to rate the degree of guilt from the perspective of the victim or perpetrator.
Cold cognitive tasksBehavioural
- Montreal Cognitive Assessment (MoCA) - This will ask participants questions related to their cognition such as visuospatial skills, naming, memory, attention, language, and recall.
- Measurement of Everyday Cognition (ECog) - This scale will ask participants about their everyday memory, language, visuospatial ability, organization, and divided attention.
- Test of Premorbid Function (TOPF) - This test will evaluate memory performance and abilities of stud participants before onset pre-morbid status.
- California Verbal Learning Test -3rd Edition (CVLT-3) -This test will measure verbal learning and memory of study participants.
- Three tests from the Delis-Kaplan Executive Function System (D-KEFS; Verbal Fluency, Color-Word Interference, and Tower Tests). -These measures assess word finding and problem-solving ability.
Structural magnetic resonance imaging (sMRI)Other
This is a non-invasive procedure to assess the structure and function of participant's brain. Structural neuroanatomical data will be acquired using structural magnetic resonance. Imaging (sMRI) with the University of Texas Southwestern (UTSW) 3T (three Tesla field) MRI scanner. Prior to participation, the investigator's team will screen participant's to ensure eligibility to participate in the sMRI scan.
Magnetoencephalography imaging (MEG)Other
This is a non-invasive procedure to measure participant's brain activity. Participants will be sitting inside the machine in a chamber, with more space than a traditional MRI machine. A hat will be placed on top of participant's head which records their brain activity. Resting-state and task-based MEG recordings will occur in a three-layer magnetically shielded room (MSR) following our UTSW Advanced Neuroscience Imaging Research (ANSIR) established procedures. Before the scan, five coils will be secured to participant's head and a three-dimensional (3D) digitizer will be used to map the location of the coils, fiducials, and scalp surface. During recording, an electric current with a unique frequency label (i.e., 320 Hz) will be fed to each coil, which will permit real time head location tracking and subsequent offline head motion correction.
four self-report forms per the requirement of the NIH Common Data Elements projectBehavioural
- DSM-5 Level 1 Cross Cutting Symptom Measure - Adult Report; a measure of multiple psychiatric symptoms, 2) Generalized Anxiety Disorder-7 (GAD-7; a measure of anxiety symptom severity), 3) Patient Health Questionniare-9 (PHQ-9; a measure of depression symptom severity), and 4) World Health Organization Disability Assessment Scale-2.0 (WHODAS-2.0; a measure of overall general functional status)
Four self-report measures to assess interpersonal functioningBehavioural
- Social Adjustment Scale - Self-report Short Form (SAS-SR: Short), 2) Inventory of Interpersonal Problems (IIP-64), 3) Social Network Index (SNI), 4) Interpersonal Support Evaluation List - 12 Items (ISEL-12).
Clinical assessmentsBehavioural
A Demographic and a Medical History Form will be completed. The Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) is a structured psychiatric interview that will confirm presence of MDD and any exclusionary neuropsychiatric disorders. To measure depression symptoms/severity, primarily we will use the Clinician Rated Inventory of Depressive Symptomatology (IDS-C), Menstrual history and pregnancy tests for female participants.
ATHFOther
Psychotropic medication use/ treatment resistance level will be measured/documented with the Antidepressant Treatment History Form-Short-Form (ATHF-SF)
| Study group | Role | What they receive |
|---|---|---|
| Major Depressive Disorder (MDD) Participants: | 1. Male and female subjects
2. Age between 21-80 years old
3. Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
4. Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
5. Able to read, write, and comprehend English
6. 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. Receives: Behavioral: Hot Cognitive Task; Behavioral: Cold cognitive tasks; Other: Structural magnetic resonance imaging (sMRI); Other: Magnetoencephalography imaging (MEG); Behavioral: four self-report forms per the requirement of the NIH Common Data Elements project; Behavioral: Four self-report measures to assess interpersonal functioning; Behavioral: Clinical assessments; Other: ATHF | |
| Healthy Volunteer Participants: | 1. Male and female subjects
2. Age between 21-80 years old
3. Able to read, write, and comprehend English
4. Provide informed consent; willing to comply with study protocol Receives: Behavioral: Hot Cognitive Task; Behavioral: Cold cognitive tasks; Behavioral: four self-report forms per the requirement of the NIH Common Data Elements project; Behavioral: Four self-report measures to assess interpersonal functioning; Behavioral: Clinical assessments |
What is being measured
The primary outcome is the main question the study is designed to answer.
Emotion Processing Domain: Emotional Intensity Morphing Task
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).
Measured: baseline visit, total time= 5 minutes
Emotion Processing Domain: Emotional Recognition Task-Eyes
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).
Measured: baseline visit, total time= 12 minutes
Emotion Processing Domain: Face Affective Go No-Go
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).
Measured: baseline visit, total time= 6 minutes
Reward Processing and Learning: Adapted Cambridge Gambling Task
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.
Measured: baseline visit, total time= 10 minutes
Reward Processing and Learning: Reinforcement Learning Task
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.
Measured: baseline visit, total time= 10 minutes
Impulsivity: Discounting Task
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.
Measured: baseline visit, total time= 7 minutes
Social Cognition: Moral Emotions Task
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).
Measured: baseline visit, total time= 13 minutes
Secondary outcomes (8)
Montreal Cognitive Assessment (MoCA): Cold Cognitive Function Testing.
Description: Cold cognitive function will be measured by Montreal Cognitive Assessment (MoCA). MoCA assesses multiple cognitive domains: attention, concentration, executive functions, memory, language, visuospatial skills, abstraction, calculation and orientation. Possible scores range from 0-30, where score ≥ 26 is considered to be normal.
Measured: Day 1/baseline
Everyday Cognition (ECog): Cold Cognitive Function Testing
Cold cognitive function will be measured by Everyday Cognition (ECog), ECog scale is a validated informant-rated questionnaire that includes one global factor and six domain-specific factors: 6 domains: everyday memory, language, visuospatial and perceptual abilities, planning, organization, and divided attention. Each item is scored based on a four-point scale: 1 = better or no change compared to 10 years earlier; 2 =questionable/occasionally worse; 3 = consistently a little worse; 4 = consistently much worse. The total score will be calculated as the sum of all 39 items. Higher scores indicates worse daily function
Measured: Day 1
Test of Premorbid Function (TOPF): Cold Cognitive Function Testing
Cold cognitive function will be measured by Test of Premorbid Function (TOPF), TOPF estimates an individual's pre-morbid cognitive and memory functioning. Possible scores range from 80 - 130, where higher scores indicate better pre-morbid cognitive functioning.
Measured: Day 1
California Verbal Learning Test-3 (CVLT-3): Cold Cognitive Function Testing
Cold cognitive function will be measured by California Verbal Learning Test-3 (CVLT-3), CVLT-3 measures verbal learning and memory. Possible scores range from 0 - 16, where higher scores indicate better performance.
Measured: Day 1
Delis-Kaplan Executive Function System (DKEF)-Color-Word Interference: Cold Cognitive Function Testing
Cold cognitive function will be measured by Delis-Kaplan Executive Function System (D-KEF) Color-Word Interference, it is made up of color naming, word reading, and inhibition, is measured in seconds, a smaller number represents a better outcome.
Measured: Day 1
Delis-Kaplan Executive Function System (DKEF)-Tower Test: Cold Cognitive Function Testing
Cold cognitive function will be measured by D-KEF Tower test, it is a measure of executive function. Total achievement scores indicate the highest score participants scored on the test. Possible score range from 0 - 30, higher scores indicate better performance.
Measured: Day 1
Delis-Kaplan Executive Function System (D-KEF)-Verbal Fluency Performance: Cold Cognitive Function Testing
Cold cognitive function will be measured by D-KEFs Verbal Fluency Test, made up of letter fluency and category fluency, is measured by number of responses, a larger number represents a better outcome.
Measured: Day 1
MEG: Magnetoencephalography
Six minutes, eyes-open resting-state scan and eighteen minutes of task-based scan will be completed. Participants will be inside the MEG scanner room for 25-30 minutes. Before the scan, five coils will be secured to the participant's head and 3D digitizer will be used to map the location of the coils, fiducials, and scalp surface, MEG data will be co-registered to their high-resolution structural T1-weighted MRI. This will provide a four-dimensional (4D) image of brain activity, similar to Functional magnetic resonance imaging (fMRI).
Measured: Baseline Day1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2023
- Study start11 Dec 2023
- Primary completion1 Jun 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The University of Texas at Arlington, National Institute of Mental Health (NIMH), JERRY M LEWIS MENTAL HEALTH RSRCH FDTN
- Responsible party
- Principal investigator, Shawn McClintock, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05966532
- Sponsor's protocol ID
- STU-2021-1131
- Other IDs
- R21MH130870
- Acronym
- ENSURE
- Status last verified
- Jul 2026
- First submitted
- 21 Jul 2023
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression (ENSURE; R21 MH130870)
- ClinicalTrials.gov ID
- NCT05966532
- Acronym / sponsor ID
- ENSURE / STU-2021-1131
- Keywords
- Emotional Cognition
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- The University of Texas at Arlington, National Institute of Mental Health (NIMH), JERRY M LEWIS MENTAL HEALTH RSRCH FDTN
- Study start
- 11 Dec 2023 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 28 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
H1.1. Adults with MDD compared to healthy controls will have significantly greater hot and cold cognitive dysfunction as measured by a Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition (EMOTICOM) and the California Verbal Learning Test - Third Edition (CVLT-3)/Delis-Kaplan Executive Function System (D-KEFS), respectively.
H1.2. Age will be associated with greater hot and cold cognitive dysfunction.
Aim 2. Establish and compare specific brain networks underlying hot and cold cognitive tasks.
H2.1. EMOTICOM Emotion Recognition and Categorization task scores will be associated with resting-state and task-based MEG connectivity metrics in the salience network,
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Major Depressive Disorder (MDD) Participants: | – | Behavioral: Hot Cognitive Task, Behavioral: Cold cognitive tasks, Other: Structural magnetic resonance imaging (sMRI), Other: Magnetoencephalography imaging (MEG), Behavioral: four self-report forms per the requirement of the NIH Common Data Elements project, Behavioral: Four self-report measures to assess interpersonal functioning, Behavioral: Clinical assessments, Other: ATHF1. Male and female subjects 2. Age between 21-80 years old 3. Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview 4. Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14 5. Able to read, write, and comprehend English 6. 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. |
| Healthy Volunteer Participants: | – | Behavioral: Hot Cognitive Task, Behavioral: Cold cognitive tasks, Behavioral: four self-report forms per the requirement of the NIH Common Data Elements project, Behavioral: Four self-report measures to assess interpersonal functioning, Behavioral: Clinical assessments1. Male and female subjects 2. Age between 21-80 years old 3. Able to read, write, and comprehend English 4. Provide informed consent; willing to comply with study protocol |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Investigators will study 120 participants aged 21-80 years old with major depressive disorder (MDD). Participants with MDD will undergo clinical and neurocognitive assessment, and MEG/MRI procedures at one time point. Investigators team 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, research teams 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hot Cognitive Task1. Emotion processing: * Participants will be shown a series of faces that appear quickly and be asked to identify what emotion is shown. * Participants will be shown a face of an emotion and indicate if participant can see the emotion changing. * Participant will be shown a series of emotions and asked to respond to only a specific emotion. 2. Motivation reward and processing: * Participant will play with a simulated roulette and make a bet to evaluate their decision-making behavior. * Participant will be shown colored circles and choose the one more likely to win money. 3. Impulsivity: • Participant will be shown a series of stimuli where they will be asked to respond to the correct stimulus. 4. Social cognition: * Participant will be shown a series of moral situations in which a character is accidentally or intentionally harmed and be asked to rate the degree of guilt from the perspective of the victim or perpetrator. | Behavioural | Healthy Volunteer Participants:, Major Depressive Disorder (MDD) Participants: |
| Cold cognitive tasks* Montreal Cognitive Assessment (MoCA) - This will ask participants questions related to their cognition such as visuospatial skills, naming, memory, attention, language, and recall. * Measurement of Everyday Cognition (ECog) - This scale will ask participants about their everyday memory, language, visuospatial ability, organization, and divided attention. * Test of Premorbid Function (TOPF) - This test will evaluate memory performance and abilities of stud participants before onset pre-morbid status. * California Verbal Learning Test -3rd Edition (CVLT-3) -This test will measure verbal learning and memory of study participants. * Three tests from the Delis-Kaplan Executive Function System (D-KEFS; Verbal Fluency, Color-Word Interference, and Tower Tests). -These measures assess word finding and problem-solving ability. | Behavioural | Healthy Volunteer Participants:, Major Depressive Disorder (MDD) Participants: |
| Structural magnetic resonance imaging (sMRI)This is a non-invasive procedure to assess the structure and function of participant's brain. Structural neuroanatomical data will be acquired using structural magnetic resonance. Imaging (sMRI) with the University of Texas Southwestern (UTSW) 3T (three Tesla field) MRI scanner. Prior to participation, the investigator's team will screen participant's to ensure eligibility to participate in the sMRI scan. | Other | Major Depressive Disorder (MDD) Participants: |
| Magnetoencephalography imaging (MEG)This is a non-invasive procedure to measure participant's brain activity. Participants will be sitting inside the machine in a chamber, with more space than a traditional MRI machine. A hat will be placed on top of participant's head which records their brain activity. Resting-state and task-based MEG recordings will occur in a three-layer magnetically shielded room (MSR) following our UTSW Advanced Neuroscience Imaging Research (ANSIR) established procedures. Before the scan, five coils will be secured to participant's head and a three-dimensional (3D) digitizer will be used to map the location of the coils, fiducials, and scalp surface. During recording, an electric current with a unique frequency label (i.e., 320 Hz) will be fed to each coil, which will permit real time head location tracking and subsequent offline head motion correction. | Other | Major Depressive Disorder (MDD) Participants: |
| four self-report forms per the requirement of the NIH Common Data Elements project1) DSM-5 Level 1 Cross Cutting Symptom Measure - Adult Report; a measure of multiple psychiatric symptoms, 2) Generalized Anxiety Disorder-7 (GAD-7; a measure of anxiety symptom severity), 3) Patient Health Questionniare-9 (PHQ-9; a measure of depression symptom severity), and 4) World Health Organization Disability Assessment Scale-2.0 (WHODAS-2.0; a measure of overall general functional status) | Behavioural | Healthy Volunteer Participants:, Major Depressive Disorder (MDD) Participants: |
| Four self-report measures to assess interpersonal functioning1) Social Adjustment Scale - Self-report Short Form (SAS-SR: Short), 2) Inventory of Interpersonal Problems (IIP-64), 3) Social Network Index (SNI), 4) Interpersonal Support Evaluation List - 12 Items (ISEL-12). | Behavioural | Healthy Volunteer Participants:, Major Depressive Disorder (MDD) Participants: |
| Clinical assessmentsA Demographic and a Medical History Form will be completed. The Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) is a structured psychiatric interview that will confirm presence of MDD and any exclusionary neuropsychiatric disorders. To measure depression symptoms/severity, primarily we will use the Clinician Rated Inventory of Depressive Symptomatology (IDS-C), Menstrual history and pregnancy tests for female participants. | Behavioural | Healthy Volunteer Participants:, Major Depressive Disorder (MDD) Participants: |
| ATHFPsychotropic medication use/ treatment resistance level will be measured/documented with the Antidepressant Treatment History Form-Short-Form (ATHF-SF) | Other | Major Depressive Disorder (MDD) Participants: |
Primary outcome
Emotion Processing Domain: Emotional Intensity Morphing Task
Time frame: 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).
Emotion Processing Domain: Emotional Recognition Task-Eyes
Time frame: 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
Time frame: 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).
Reward Processing and Learning: Adapted Cambridge Gambling Task
Time frame: 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
Time frame: 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.
Impulsivity: Discounting Task
Time frame: 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.
Social Cognition: Moral Emotions Task
Time frame: 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).
8 secondary outcomes
Montreal Cognitive Assessment (MoCA): Cold Cognitive Function Testing.
Time frame: Day 1/baseline
Everyday Cognition (ECog): Cold Cognitive Function Testing
Time frame: Day 1
Test of Premorbid Function (TOPF): Cold Cognitive Function Testing
Time frame: Day 1
California Verbal Learning Test-3 (CVLT-3): Cold Cognitive Function Testing
Time frame: Day 1
Delis-Kaplan Executive Function System (DKEF)-Color-Word Interference: Cold Cognitive Function Testing
Time frame: Day 1
Delis-Kaplan Executive Function System (DKEF)-Tower Test: Cold Cognitive Function Testing
Time frame: Day 1
Delis-Kaplan Executive Function System (D-KEF)-Verbal Fluency Performance: Cold Cognitive Function Testing
Time frame: Day 1
MEG: Magnetoencephalography
Time frame: Baseline Day1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social CognitionLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder (MDD) and Healthy Adult Volunteer, run by University of Texas Southwestern Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Emotion Processing Domain: Emotional Intensity Morphing Task (time frame: baseline visit, total time= 5 minutes). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.