Farmington,
Connecticut
06030
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.
Study summary:
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.
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