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Cognitive Dysfunction in Patients with Remitted Depression: Preliminary Results

Posted on 26 August 2015 in Research

Author: Muzaffer Kaser

The British Association for Psychopharmacology Summer Meeting was held in Bristol between 26-29 July this year. It was a vibrant meeting bringing together many clinicians and researchers from the fields of psychopharmacology, psychiatry, neuroscience and psychology.

I had the opportunity to present preliminary findings on cognitive functions in patients with remitted depression from our ongoing study. Sharing the study poster on social media sparked interest in finding out more. This blog post addresses comments from social media and shares the findings. Whether you are a researcher within this field, have experienced depression yourself or know someone else who suffers with it, this post shares my research findings.

I am a psychiatrist currently doing my PhD at the Department of Psychiatry, University of Cambridge supervised by Professor Barbara Sahakian. Our research focuses on cognitive functions in depression for a number of reasons. Firstly, cognitive functions such as attention, memory and planning are affected in patients with depression1. It has increasingly been recognised that cognitive dysfunction represents a distinct dimension of depressive illness, rather than a product of low mood. This view was further supported by the findings that cognitive dysfunction continues in patients with depression even after recovery2. Secondly, persistent cognitive problems are associated with poorer occupational/social functioning and increased risk of relapse in patients with depression3. In this particular study, we are aiming to investigate the effectiveness of modafinil on a range of cognitive functions (e.g. attention, memory, planning).

Modafinil is a medication which is originally licenced for sleep disorders (e.g. narcolepsy). However, it has become a focus of interest for psychiatry as it was shown to improve cognitive functions in healthy people as well as patients with neuropsychiatric disorders4.  Our aim in this proof-of concept study is to understand the feasibility of using modafinil to improve cognitive functions in patients who have recovered from depression. The study involves two sessions: the first session measures baseline cognitive functions, during the second session patients receive either modafinil or placebo (inactive pill) and complete a battery of CANTAB cognitive tasks. It is a double-blind placebo controlled study which is deemed as the most reliable way to understand effectiveness of an intervention.

The cognitive measures used in this study are from the CANTAB computerised neuropsychological battery. CANTAB has been used in hundreds of research studies and has the advantage of providing standardized computerized measures which are sensitive to pharmacological interventions. During baseline testing patients completed the following four CANTAB tasks:

  • Stockings of Cambridge (measure of planning and executive function)
  • Spatial Working Memory (measure of working memory)
  • Paired Associates Learning (measure of episodic memory)
  • Rapid Visual Information Processing (measure of sustained attention)

All four tests have been widely used in research studies into depression and they also have normative data available from hundreds of healthy volunteers. This provides the opportunity to compare a single participant's performance with a properly matched peer group (matched for age, gender, IQ) and give a standard score for their performance for a particular test..

We presented our preliminary results from the baseline session at the BAP 2015 meeting. Data from 38 participants (21 female, 17 male) was available for this. Based on the recent meta-analysis of CANTAB test performance in patients with depression5, a score of 0.5 standard deviations below the average was set as a cut-off to define patients with cognitive dysfunction. According to this cut-off, cumulative percentages of patients who scored below the cut-off were as follows:

  • Attention (RVP): 57.6%
  • Executive Function (SOC): 51.4%
  • Working Memory (SWM): 37.8%
  • Episodic Memory (PAL): 14.3%

These preliminary results indicated that at least half of the patients in our sample showed cognitive dysfunction in executive function and attention domains. Working memory was affected to a lesser extent and visual episodic memory was least affected.

Cognitive dysfunction at the remission phase of depression is a significant problem as it can interfere with daily functioning, for example at work or in social settings and could potentially lead to further relapses6. Currently, there are no available treatments to address cognitive dysfunction in depression. Modafinil was previously shown to improve executive function and attention . Prospective results from our study will allow us to determine whether modafinil can mitigate executive function and attention problems in patients with remitted depression and aid decisions on whether further studies are required.­

This research work was completed at the Behavioural and Clinical Neuroscience Institute which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). Dr Muzaffer Kaser is supported by Cambridge-IDB International Scholarship and his affiliated institution Bahcesehir University.


References:

  1. Porter, R. J., Bourke, C., & Gallagher, P. (2007). Neuropsychological impairment in major depression: its nature, origin and clinical significance. Australian and New Zealand Journal of Psychiatry, 41(2), 115-128.
  2. Bora, E., Harrison, B. J., Yücel, M., & Pantelis, C. (2012). Cognitive impairment in euthymic major depressive disorder: a meta-analysis. Psychological medicine, 43(10), 2017-2026.
  3. McIntyre, Roger S., et al. "Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions." Depression and anxiety 30.6 (2013): 515-527.
  4. Minzenberg, M. J., & Carter, C. S. (2008). Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology, 33(7), 1477-1502.
  5. Majer, M., Ising, M., Künzel, H., Binder, E. B., Holsboer, F., Modell, S., & Zihl, J. (2004). Impaired divided attention predicts delayed response and risk to relapse in subjects with depressive disorders. Psychological medicine, 34(08), 1453-1463.