Predictors of Cognitive Outcomes in Geriatric Depression

Purpose

This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Understanding how effects of stress in older depressed adults, as well as factors that might minimize those effects, lead to particular mood and cognitive outcomes will inform future development of novel prevention strategies.

Conditions

  • Major Depressive Disorder
  • Neuroticism
  • Cognitive Change
  • Stress

Eligibility

Eligible Ages
Over 60 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • major depression, single episode or recurrent; - ability to read and write English; - Mini-Mental State Examination >25.

Exclusion Criteria

  • lifetime alcohol/drug dependence - conditions associated with brain abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc. - untreated endocrine disorder other than diabetes mellitus - established clinical diagnosis of dementia - other primary psychiatric disorders, e.g., panic disorder, social phobia, obsessive- compulsive disorder, schizoaffective disorder, schizophrenia, bipolar disorder

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
Naturalistic study using FDA approved antidepressants to examine the effects of stress and neuroticism on outcomes
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
Depressed
Subjects receive FDA-approved antidepressants
  • Drug: Sertraline, bupropion, desvenlafaxine
    Study geriatric psychiatrists prescribe FDA-approved antidepressants using a treatment algorithm consistent with the STAGED (Duke Somatic Treatment Algorithm for Geriatric Depression) approach, with standardization of treatment in the first six months beginning with sertraline, with the option of augmentation with bupropion or switch to desvenlafaxine. Beyond six months of acute treatment, subjects are treated based on the study psychiatrist's clinical assessment and recommendations, consistent with STAGED guidelines.
    Other names:
    • Zoloft
    • Wellbutrin
    • Pristiq

Recruiting Locations

More Details

Status
Recruiting
Sponsor
David Steffens

Study Contact

Judy Anderson
860-679-7571
judanderson@uchc.edu

Detailed Description

In this renewal of R01MH108578, the investigators are seeking to extend findings from the initial study to focus on effects of stress in longitudinal mood and cognitive outcomes of late-life depression (LLD) and to examine stress effects on brain structure and function in LLD. Severe or persistent stressors can result in a number of behavioral and mood changes, including anxiety, dysphoric mood, sleep disruption, altered appetite, and withdrawal from social and pleasurable activities. These stress-related consequences are particularly salient when considering longitudinal outcomes of treated LLD. They may be compounded by an individual's longstanding maladaptive patterns of response to stress, embodied in the construct of neuroticism, which the investigators have shown to be related to poor mood and cognitive LLD outcomes. Moreover, Andreescu et al. (2019) introduced a model of depression recurrence that incorporates the homeostatic disequilibrium hypothesis, which proposes that in geriatric remitted depression, neural networks are in fragile homeostasis that is threatened by stress exposure. Networks of particular importance in stress of LLD outcome are the Default Mode Network (DMN), Salience Network (SN) and Executive Control Network (ECN). The Neurobiology of Late Life Depression (NBOLD) study began enrolling older depressed and never depressed controls in 2013, enrolling 132 depressed and 44 controls, and currently follows 77 depressed and 22 controls. Subjects are well characterized in terms of mood, cognition, personality and stress (including specific measures obtained during the present COVID pandemic). It is well suited to examine stress effects on longitudinal mood and cognitive outcomes. For the renewal, the study will follow current subjects and recruit 75 new subjects, who will be followed for up to 5 years with annual cognitive testing, stress measures and baseline and two-year functional brain magnetic resonance imaging (fMRI) scan. In this renewal, the investigators will examine the following specific aims: 1. To study effects of stressors (obtained on a variety of measures) and neuroticism on longitudinal mood and cognitive outcomes in older adults with history of major depressive disorder (MDD). 2. To study effects of stress and neuroticism on brain structure and function in older adults with MDD history. 3. To explore relationships among variables in Aims 1 and 2 with longitudinal multivariable statistical models.