Novel targets for memory impairment in depression: Harnessing the potential of coupled sleep oscillations

Research Spotlight Blog No. 13

Dr Alexandra Stainton is a Postdoctoral Research Fellow at Orygen, the University of Melbourne's Centre for Youth Mental Health and the largest mental health service in Victoria, Australia. Across almost 5-years postdoctoral research experience, Dr Stainton has managed both clinical trials and large research projects all centred around optimising treatments for young people in the early course of mental illness. Her current research focuses on optimising cognitive health (e.g., thinking, memory, attention, etc.) to enhance young people’s long-term recovery.

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Depression is the leading cause of disability in young people aged 10-24 worldwide¹, and one in five people will experience depression by early adulthood². Individuals who experience depression can also experience significant difficulties with their memory³, and these memory difficulties can subsequently impact other areas of life like work, study, friendships, and overall quality of life⁴. Young people with depression have told us (in both a national survey⁵ and in qualitative studies⁶) that addressing these memory difficulties are a high treatment priority for them. However, these memory difficulties aren’t addressed by standard treatments for depression (such as medication and talking therapy). It is also not well known when and how memory difficulties develop in depression. As such, there is a desperate need for researchers to gain a deeper understanding of why these memory difficulties occur, and how we might be able to treat them effectively.

"I can't remember birthdays, I can't remember like important school days, I can't... like I forgot quite a few of my psychology appointments" - Quote from a young person with depression

One potential avenue to deepen our understanding of memory difficulties in depression is by exploring sleep. Sleep is also often significantly disrupted in depression and plays a key role in memory consolidation (the transfer of temporary memories to long-term storage). Young people with depression have also told us that they would be highly likely to try a sleep intervention to improve their thinking and memory⁵. During deep sleep, the brain produces different kinds of electrical waves. Two of these waves, one slow and one fast, appear to be particularly important for the process of memory consolidation overnight. Sleep Spindles are brief (~1-3s) powerful bursts of electrical activity, whereas Slow Oscillations are large amplitude waves which alternate between an “upstate” and a “downstate”. Recent research suggests it is the coupling (i.e., sleep spindles occurring close to the peak upstate of a slow oscillation) of these brain waves during sleep that facilitates the transfer of new memories to longer-term storage⁷.

Sleep waves

Funding from the Circadian Mental Health Network’s Early Career Researcher Pilot Project scheme has allowed me to start up a new pilot study investigating the relationship between coupled sleep oscillations and overnight memory consolidation in youth depression. This pilot study is a collaboration between Orygen and the John Trinder Sleep Laboratory at the University of Melbourne. Forty-two young people (aged 16-25) are being recruited from primary mental health services, through university mental health clinics, and from the community. Participants will represent one of two groups: people who have experienced depression in the past two years, and healthy controls who have not experienced mental health difficulties. Participants complete pre-sleep memory training and testing, before being set up with an EEG sleep recording device (which measures brain waves through electrodes stuck to the scalp) and returning to their own homes to sleep overnight. The following morning, they return to the sleep lab to re-do the memory tests. We are interested to see whether the degree of coupling (how closely sleep spindles are occurring to the peak upstate of slow oscillations) is associated with the degree to which someone’s memory improves following a night of sleep and whether these sleep parameters differ between the depression and healthy control group.

This study addresses a pressing global challenge in youth mental health. Memory difficulties, a key driver of depression-related disability, are overlooked by standard treatment, but are highly important to young consumers. Developed in consultation with young consumers, this pilot will provide preliminary data on whether these coupled brain waves working in harmony may be a novel biomarker of memory impairment in depression and has the potential to pave the way for novel sleep therapies to target coupled sleep oscillations such as transcranial alternating current stimulation, targeted memory reactivation, closed loop home-based auditory stimulation, and novel pharmaceuticals for depression. The hope is that novel strategies to reduce memory difficulties could improve the day-to-day lives of young people with depression.

Blog by Alexandra Stainton

References

1. Gore FM, et al. Global burden of disease in young people aged 10-24 years: a systematic analysis. Lancet (London, England). 2011;377(9783):2093-102.

2. Kessler RC, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry. 2005;62(6):593-602.

3. Ahern E, et al. Cognitive functioning in the first-episode of major depressive disorder: A systematic review and meta-analysis. Neuropsychology. 2017;31(1):52-72.

4. Cambridge OR, et al. The clinical relationship between cognitive impairment and psychosocial functioning in major depressive disorder: A systematic review. Psychiatry Research. 2018;269:157-71.

5. Bryce S, et al. Cognitive health treatment priorities and preferences among young people with mental illness: The your mind, your choice survey. Early Intervention in Psychiatry. 2023;18(2):94-101.

6. Morey-Nase C, et al. Subjective experiences of neurocognitive functioning in young people with major depression. BMC Psychiatry. 2019;19(1):1-9.

7. Klinzing JG, et al. Mechanisms of systems memory consolidation during sleep. Nature neuroscience. 2019;22(10):1598-610.