Early findings from a study of recurring late-life depression after successful treatment suggests that tactics such as stress reduction and greater social support may help disrupt the cycle.
The REMBRANDT study, a two-year observational study of recurring late-life depression, aims to understand the relationships between clinical, cognitive, environmental, and neurobiological factors as contributors to depression recurrence and its possible predictors.
A new publication in Psychological Medicine reports on the multi-site study’s initial findings.
“People with late-life depression often have recurrent depressive episodes despite receiving ongoing care and maintenance treatment. However, it is unclear whether the clinical and cognitive characteristics we see during remission might predict future recurrence,” said Warren Taylor, M.D., James G. Blakemore Professor of Psychiatry and Behavioral Sciences at Vanderbilt University Medical Center and lead author of the study.
“People with late-life depression often have recurrent depressive episodes despite receiving ongoing care and maintenance treatment.”
Common among people over 60, late-life depression is characterized by increased disability, medical comorbidity, suicide risk, and higher mortality. It is also associated with poor or impaired cognitive function, with an increased risk for dementia.
Taylor, a geriatric psychiatrist, has been studying late-life depression for more than two decades. His work uses neuroimaging and neurocognitive methods to advance the understanding of the pathogenesis of depression and its long-term consequences.
“In the REMBRANDT study, we carefully characterized people who were treated for depression and were doing fairly well,” Taylor said. “Once in the study, we continued providing treatment and clinically assessed the participants every two months.”
In addition to clinical assessment, structural and functional brain imaging occurred every eight months.
“We wanted to combine all the data – the best measures across everything that would prevent relapse.”
Neuropsychological Testing
REMBRANDT participants included 135 patients with remitted late-life depression and 69 comparison subjects. The goal was to collect phenotypic data to help identify vulnerability and resilience factors and to stratify individual clinical risk.
Based on a previous study that explored the predictors for recurrence of late-life depression, the investigators hypothesized that higher risk would be associated with greater depressive-symptom severity, greater stress exposure, lower levels of social support, and greater difficulty performing activities of daily living.
Deep symptom phenotyping and two weeks of “burst” assessments were conducted to determine variability in symptoms and cognitive performance. The relapsing group exhibited greater antidepressant treatment intensity, along with greater fatigue, rumination, disability, and higher systolic blood pressure.
“A big predictor of relapse is how difficult is it to get someone better – whether they need a combination of medicines,” Taylor said. “During the study, if a participant needed more or different medicines, we gave it to them.”
Sixty, or 44 percent, of the REMBRANDT participants had a relapse during the two-year period.
As hypothesized, those who relapsed reported higher levels of external stressors and less social support. They also showed differences in how they responded to laboratory stress. “We saw this both in the brain and in the physiologic response,” Taylor said.
Another factor considered was how memory abilities affected relapse.
People with late-life depression often have memory issues, but REMBRANDT did not find poorer performance on memory tests as predictive of relapse, Taylor noted.
“Memory measures may change over the course of the study, but we would hope that people who stay in remission may see improvements in memory over time.”
Deeper Dive into Biomarkers
In a study published in Neuropsychopharmacology, Taylor and colleagues examined both brain and cardiovascular responses to acute stressors.
“We hoped to improve our understanding of how alterations in neural circuits and cardiovascular markers that persist during remission contribute to depression recurrence,” Taylor said.
“Individuals who stay remitted for two years keep getting better. As time goes on, it solidifies the remittance. For people who relapse, things get worse.”
Participants who maintained remission had a “blunted” response to stressors, but this may be more sustainable, the study found.
“They don’t respond as strongly when they encounter a new stressor.”
Taylor says the research emphasizes the need for clinically translatable relapse biomarkers to inform late-life depression care. He hopes they can continue to follow participants longitudinally to better understand indicators of impending relapse.
“Individuals who stay remitted for two years keep getting better,” he added. “As time goes on, it solidifies the remittance. For people who relapse, things get worse – they stay symptomatic, despite our best efforts to treat their condition.”
