Clinical trial NCT05273996: Predictors of Cognitive Outcomes in Geriatric Depression
Official title: Phenotype Predictors of Cognitive Outcomes in Geriatric Depression
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Major Depressive Disorder
Neuroticism
Cognitive Change
Stress
Keywords: Late Life Depression
Lead sponsor: UConn Health
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-03-10
Enrollment: 75
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Naturalistic study using FDA approved antidepressants to examine the effects of stress and neuroticism on outcomes
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRAS)
timeFrame: Three years
measure: Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Battery Total Score
timeFrame: Three years
measure: Cognitive clinical diagnosis
timeFrame: three years
Secondary outcomes:
measure: Functional brain magnetic resonance imaging (fMRI) scan changes in resting state functional connectivity.
timeFrame: Two years
measure: Functional brain magnetic resonance imaging (fMRI) scan structural imaging changes
timeFrame: Two years
Other outcomes:
measure: Neuroticism subtest score on NEO Personality Inventory
timeFrame: Three years
Locations:
city: Farmington
country: United States
facility: UConn Health
state: Connecticut
Study officials:
affiliation: UConn Health
name: David Steffens, M.D., M.H.S.
role: PRINCIPAL_INVESTIGATOR
References: