Neurobehavioral Mechanisms of Emotion Regulation in Depression Across the Adult Lifespan

Study Overview
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Brief Summary
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The aim of this study is to test a model of demographic (age, sex), clinical, cognitive, and neurocircuitry predictors of emotion regulation ability and long-term depressive symptoms.

Detailed Description
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Emotion regulation capacities are crucial for sustaining mental health in the face of cumulative stressors over one's lifetime. Although it is well documented that some emotion regulation abilities are preserved or even improved in healthy aging, little is known about why regulatory deficits persist in older adults who suffer from depression. Treatments for major depressive disorder (MDD) focus on remediating affective dysregulation processes that confer risks for disability, poor quality of life, and morbidity into late life. Theoretical perspectives on emotional aging propose myriad lifespan changes that potentially impact regulatory capacities, including structural and functional integrity of dorsal attentional and ventral affective processing pathways, cognitive status, and use of specific regulatory strategies, among others. However, there is a dearth of empirical evidence to indicate which combination of these factors critically interacts with depressive symptoms to impact emotional dysregulation in older adults, when these factors become important across the course of the adult lifespan, which strategies they apply to, and whether they can predict future depression status. Thus, the goal of this specific application is to test a comprehensive model of age-related changes to brain circuitry, neurocognitive performance, and social support as predictors of emotion regulation abilities and depressive symptoms in individuals with and without MDD. Reappraisal and distraction are the emotion regulation strategies of primary interest. Models will be evaluated using primarily a series of linear (multiple) regression models focusing on between-subject effects/comparisons (age, MDD status, etc.) and the emotion regulation outcomes separately for reappraisal and distraction processes. As an extension of these models we will perform Structural Equation Modeling (SEM) type modeling to summarize the liability dimensions underlying the specific domains of depression [BDI scores measuring depression severity; lifetime duration of depressive episode(s)], and neural measures of dorsal attention network functioning [gPPI connectivity between dlPFC and amygdala; task-based activation during distraction in dACC, dlPFC, and inferior parietal lobe; DTI FA measure in SLF II] and affective network functioning [gPPI connectivity between vlPFC and amygdala; task-based activation during reappraisal in vmPFC, vlPFC, and amygdala; DTI FA measure of UF]. The SEM will be especially useful in predicting the future depression that will be assessed at one-year follow up, where the predicted (best linear unbiased predictors-BLUPS) values of lower-dimensional latent traits, along with emotion regulation outcomes, can be used as predictors for future depression. Moreover, hierarchical modeling structures can be imposed on latent traits conditionally on a shared latent trait describing associations among several latent traits thus further reducing underlying dimensionality and simplifying computations. This single trait can be thought as a cumulative effect of all latent traits and can be used a single index of uncertainty in predicting future depression symptom severity.

Official Title
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Neurobehavioral Mechanisms of Emotion Regulation in Depression Across the Adult Lifespan

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Procedure: fMRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 35-75 No MRI contra-indications (e.g., metal in body) Not currently pregnant Ambulatory No known uncorrected sensory deficits Estimated verbal IQ of 85+ as indicated by the North American Adult Reading test MDD group: Current MDD assessed by history of MDD as assessed by standardized SCID interview Control Group: no lifetime of history of MDD as assessed by standardized SCID interview Exclusion Criteria: History of moderate or severe substance dependence, as assessed by standardized SCID interview History of psychosis, mania, or eating disorders, as assessed by standardized SCID interview Disorders with impact on brain characteristics (e.g., epilepsy, Parkinson's Disease) or history of stroke Contraindications to MRI scanning, as indicated on the MRI safety screening questionnaire Use of antidepressants or other psychotropics other than sleep aids in the past 4 weeks (8 weeks for fluoxetine) Indication of mild cognitive impairment or dementia. To meet screening criteria, participants must meet all of the following: Scoring of 24 or higher on the Montreal Cognitive Assessment; perform above 1.5 standard deviations on the following measures: HVLT delayed recall, Trail Making B, and Animal Naming based normative values

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD patients<br>Participants ages 35-75 determined to be clinically depressed via structured clinical interview. No interventions will be administered as part of this study. | Procedure: fMRI<br>* Patients will undergo fMRI imaging to assess areas of the brain that are active during emotion regulation. No clinical benefit of MRI imaging is anticipated.<br>|
| non-MDD patients<br>Participants ages 35-75 determined to be lifetime free of psychiatric conditions as assessed by structured clinical interview. No interventions will be administered as part of this study. | Procedure: fMRI<br>* Patients will undergo fMRI imaging to assess areas of the brain that are active during emotion regulation. No clinical benefit of MRI imaging is anticipated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of emotion regulation strategy use. | Self-reported negative affect and arousal following the use of reappraisal and distraction strategies | baseline | 
| Depression symptom severity | Severity of depressive symptoms as measured by self report | 6 months | 
| Depression symptom severity | Severity of depressive symptoms as measured by self report | 12 months |