Neurobehavioral Mechanisms of Emotion Regulation in Depression Across the Adult Lifespan

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.

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