Cognition in schizophrenia and bipolar disorder: Potential mechanisms and possible therapies

At the 35th ECNP Congress in Vienna, Austria (15th−18th Oct), Dr Ingrid Melle (University of Oslo, Oslo University Hospital, Oslo, Norway) first discussed how cognitive problems can be a key feature of schizophrenia and bipolar disorder. Such problems have been linked to ‘overpruning’ of synaptic densities and to changes in thalamic activity during sleep, associated with memory consolidation. Cognitive difficulties can affect both functioning and social cognition in patients with schizophrenia or bipolar disorder. Dr Rebecca Strawbridge (institute of Psychiatry, Psychology & Neuroscience, London, UK) then discussed cognitive remediation therapy, which has been shown over the past few decades to help people develop cognitive skills that can be utilised in their everyday lives.

Cognition in schizophrenia and bipolar disorder

Cognitive problems develop early in patients with schizophrenia and bipolar disorder and may remain an issue throughout life.1,2 In cell culture models of schizophrenia, inflammation-mediated ‘overpruning’ leads to synaptic density reduction in fibroblasts compared to healthy controls.3 This may be, postulated Dr Melle, related to the cognitive deficits seen in schizophrenia.

Sleep is another factor that can affect cognition. Sleep is needed for memory consolidation,4 which involves ‘sleep spindles’ seen on EEG reflecting small bursts of activity in the thalamus during, predominantly, non-REM sleep.5 In patients with schizophrenia and bipolar disorder, sleep spindle density is decreased.6,7

Cognitive difficulties can impact functionality and social cognition

It is well established that cognition is linked to functional outcomes in patients with schizophrenia.8 As such, in the 11th revision of the International Classification of Diseases, cognitive symptoms are now included in the diagnostic description of schziophrenia.9 Cognitive deficits can not only directly impact quality of life and functioning, but also indirectly, through their effects on social cognition.10 These include domains, such as empathic accuracy, managing emotion, self-referential memory, the ability to detect lies or sarcasm and facial affect recognition.2


Improving cognition in schizophrenia and bipolar disorder

It is important to address cognitive functioning in schizophrenia and bipolar disorder to help patients gain and maintain recovery.11 Accordingly, cognitive interventions for schizophrenia and bipolar disorder have been proposed.12,13 Cognitive remediation therapy (CRT) encompasses a number of psychological/behavioural interventions aimed at cognitive rehabilitation and improving functionality.14 CRT for schizophrenia has been developed over the past 50 years. Meta-analyses showed significant cognitive gains produced by CRT, along with some effects on functioning and symptoms.15

CIRCuiTS is a type of CRT that teaches strategies and promotes metacognitive knowledge and regulation to help a patient understand and regulate their cognitive faculties. This therapy is validated in patients with schizophrenia for its ability to improve cognitive and functional outcomes. CIRCuiTS is delivered remotely in a 1:1 manner along with homework sessions. It includes goal setting and involves tasks that can be applied to real-life situations. For instance, cognitive tasks that can be abstract then can be practised online in a virtual village.16,17 While results of a large, multicentre study of CIRCuiTS is ongoing, the practical aspects of the trial have been published.18

Cognitive remediation therapy can help build cognitive faculties

CRT for bipolar disorder has a shorter history, with studies from 2010 onwards showing benefits on areas, such as problem solving and working memory.19 These include programs that extend over a number of weeks or months and include, or are only, computer-based elements.20-22 For bipolar disorder, Dr Strawbridge highlighted how large, high quality, randomised controlled trials are needed. Methodology papers are available to inform current practice. These recommend that CRT programs for patients with bipolar disorder target those with objectively measured cognitive impairments.22,23 CRT has also been combined with functional remediation with positive outcomes.24,25

There are few studies that investigate pharmacological therapies for cognitive difficulties in patients with schizophrenia or bipolar disorder. However, while some improvements in cognitive variables have been shown with a diverse array of agents, more studies are needed.26-28 The International Society for Bipolar Disorders Targeting Cognition Task Force also suggest other non-pharmacological options to address cognitive features of bipolar disorder including repetitive transcranial magnetic stimulation and transcranial direct current stimulation.22,29,30

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

  1. Lewandowski KE, et al. Psychol Med. 2011; 41: 225-241.
  2. Lee J, , et al. Am J Psychiatry. 2013; 170: 334-341.
  3. Sekar A, , et al. Nature. 2016; 530: 177-183.
  4. Walker MP, et al. Neuron. 2002; 35: 205-211.
  5. Klinzing JG, et al Nat Neurosci. 2019; 22: 1598-1610.
  6. Ferrarelli F, et al. Am J Psychiatry. 2007; 164: 483-492.
  7. Ritter PS, et al. Acta Psychiatr Scand. 2018; 138: 163-172.
  8. Green MF. Am J Psychiatry. 1996; 153: 321-330.
  9. World Health Organization. ICD-11 for Mortality and Morbidity Statistics (Version : 02/2022). 6A20 Schizophrenia. 6A25.5 Cognitive symptoms in primary psychotic disorders. Published 2022. Accessed: 07 Nov 2022.
  10. Fett AK, et al. Neurosci Biobehav Rev. 2011; 35: 573-588.
  11. Tsapekos D, et al. Bipolar Disord. 2020; 22: 213-215.
  12. Green MF. Am J Psychiatry. 1993; 150: 178-187.
  13. Goldberg JF, Chengappa KN. Bipolar Disord. 2009; 11 Suppl 2: 123-137.
  14. Wykes T, et al. Br J Psychiatry. 2007; 190: 421-427.
  15. Lejeune JA, et al. Schizophr Bull. 2021; 47: 997-1006.
  16. Reeder C, et al. Behav Cogn Psychother. 2016; 44: 288-305.
  17. Cella M, et al. Front Psychol. 2015 ;6: 1259.
  18. Wykes T, et al. Trials. 2018; 19: 183.
  19. Deckersbach T, et al. CNS Neurosci Ther. 2010; 16: 298-307.
  20. Strawbridge R, et al. Bipolar Disord. 2021; 23: 196-208.
  21. Ott CV, et al. Bipolar Disord. 2021; 23: 487-499.
  22. Miskowiak KW, et al. Bipolar Disord. 2022; 24: 354-374.
  23. Miskowiak KW, et al. Eur Neuropsychopharmacol. 2016; 26: 1541-1561.
  24. Gomes BC, et al. Bipolar Disord. 2019; 21: 621-633.
  25. Torrent C, et al. Am J Psychiatry. 2013; 170: 852-859.
  26. Hsu WY, et al. Front Psychiatry. 2018; 9: 91.
  27. Miskowiak KW, et al. J Clin Psychiatry. 2014; 75: 1347-1355.
  28. Burdick KE, et al. Neuropsychopharmacology. 2020; 45: 1743-1749.
  29. Myczkowski ML, et al. J Affect Disord. 2018; 235: 20-26.
  30. Bersani FS, et al. J Affect Disord. 2017; 209: 262-269.
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