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Experiences of cognitive problems such as memory loss or difficulty concentrating, known as ‘brain fog’, may not predict relapse in depression according to a new study that has confounded researchers’ expectations.
In a new paper in the BMJ Mental Health, a research team led by Dr Angharad de Cates from the University of Birmingham, along with researchers from the University of Oxford, studied data from 1,800 UK participants who had previously had an episode of depression. Participants were matched for age and sex with a control; and recruited as part of the UK Biobank. The study was funded by the Guarantors of Brain and National Institute for Health and Care Research (NIHR) through the NIHR Biomedical Research Centre: Oxford Health.
The research team tested the idea that decline in some elements of cognition such as memory and attention, which affect between 70-90% of patients with major depressive disorder (MDD), might be associated with a greater risk of relapse. With 40% of MDD patients having persistent cognitive impairment, the team looked to see whether cognitive decline could, therefore, help clinicians predict who is more likely to have further depressive episodes.
Participants were invited to take part in a series of cognitive tests and have structural and functional MRI imaging to look at whether there were any structural changes to their brains. Tests include a snap-card game to test reaction times, a numerical memory game, a word-pairing game and others. These tests looked at different areas of cognitive performance. The researchers also pooled data across the battery of tasks to generate a measure of general cognitive functioning.
The research team found that one third (33%) of participants who had previously had depression experienced at least one depressive relapse in the years following their study visit, compared to 13% of control participants having their first episode of depression.
However, the study also found that patients with previous depression who had the lowest performance across the battery of cognitive tests were less likely to relapse compared to those with the highest cognitive scores. This was contrary to expected findings, and also results seen for control participants, where worse performance on cognitive tests was associated with higher risk of depression during the follow up period.
Dr Angharad de Cates, who is an honorary member of the Department of Psychiatry at the University of Oxford, and corresponding author of the paper said:
We expected poorer cognitive performance to be associated with a higher risk of future depression in both participants with a history of depression and matched controls. However, the results were more nuanced than expected. Among people with previous depression, those with higher cognitive scores were more likely to experience a further depressive episode than those with lower scores—the opposite pattern to that observed in controls.
We think this finding points to a range of social and residual factors related to cognition that warrant further investigation in both research and clinical practice. One possible explanation is that better cognitive functioning may be needed to recognise symptoms and seek help, highlighting the importance of optimising cognition in those with previous depression to support early intervention.”
Participants from the healthy control group who took part in the study also took cognitive tests and had fMRI scans, and the results suggested that participants who performed poorly in terms of cognitive performance were at a higher risk of having an initial depressive episode.
While only 13% of participants who had no previous history of depression had an episode during the study period, fairly low in absolute terms, the lowest cognitive performing participants were 40% more likely to have had a first depressive episode compared to the baseline.
Senior author Dr Anya Topiwala, Senior Clinical Researcher at Oxford Population Health and honorary member of the Department of Psychiatry at the University of Oxford, said:
People often think of memory problems as simply a consequence of depression, but our findings suggest the relationship is more complex. Among people with a history of depression, those with better cognitive performance were actually more likely to experience future depressive symptoms. This highlights that remitted depression remains a high-risk state, and that relapse risk may not look the same across different individuals. Understanding these differences could help us design more personalised approaches to prevention and follow-up care.”
The research team are part of the Midlands Mental Health Mission, supported by NIHR Biomedical Research Centre: Oxford Health and are continuing to research ways to address cognitive loss, which is prevalent among people with major depressive disorders, and can affect short- and long-term memory, attention and focus.