Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults with Depression

Purpose

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.

Conditions

  • Major Depressive Disorder (MDD)
  • Healthy Adult Volunteer

Eligibility

Eligible Ages
Between 21 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  1. Male and female participants 2. Age between 21-80 years old 3. 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

Exclusion Criteria

  1. History of bipolar disorder, schizophrenia, or schizoaffective disorder 2. Presence of psychotic features 3. Lifetime central nervous system (CNS) disease (including head injury with loss of consciousness > 5 minutes) 4. History of neurodevelopmental disorder (e.g., Autism spectrum disorder) 5. History of medical conditions that can affect neurocognitive function as well as be confounded with age (e.g., thyroid disease, endocrine illnesses) 6. Women who are pregnant 7. Current use of medications with known impacts on neurocognitive function (e.g., acetylcholinesterase inhibitors, amphetamine, methylphenidate, vortioxetine, sedatives) 8. Alcohol/substance use disorder within past 3 months 9. DSM-5 diagnosis of major cognitive impairment 10. Current sensory or physical impairment that interferes with testing. 11. Contraindication to MRI and MEG (only for depressed participants) (e.g., any electronic / metallic implants near or within the head or body, claustrophobia)

Study Design

Phase
Study Type
Observational
Observational Model
Case-Control
Time Perspective
Cross-Sectional

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Behavioral: Hot Cognitive Task
    1. 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.
  • Behavioral: 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.
  • Other: 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: 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.
  • Behavioral: four self-report forms per the requirement of the NIH Common Data Elements project
    1) 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)
  • Behavioral: Four self-report measures to assess interpersonal functioning
    1) 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).
  • Behavioral: Clinical assessments
    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.
  • Other: ATHF
    Psychotropic medication use/ treatment resistance level will be measured/documented with the Antidepressant Treatment History Form-Short-Form (ATHF-SF)
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
  • Behavioral: Hot Cognitive Task
    1. 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.
  • Behavioral: 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.
  • Behavioral: four self-report forms per the requirement of the NIH Common Data Elements project
    1) 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)
  • Behavioral: Four self-report measures to assess interpersonal functioning
    1) 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).
  • Behavioral: Clinical assessments
    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.

Recruiting Locations

More Details

Status
Recruiting
Sponsor
University of Texas Southwestern Medical Center

Study Contact

Shawn McClintock, PhD
214-648-2806
shawn.mcclintock@utsouthwestern.edu

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,

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