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10 August 2022

Using CANTAB to examine the association of lithium and second-generation antipsychotics with neurocognition in young people with bipolar disorder

We caught up with Xinyue (Joyce) Jiang from the Centre for Addiction and Mental Health in Toronto to hear more about how her team used CANTABTM tasks to understand the effect of antipsychotic medication on cognition in young people affected by bipolar disorder.

I am a PhD student in the University of Toronto Department of Pharmacology & Toxicology, based at the Centre for Youth Bipolar Disorder (CYBD), a subspecialty clinical research program at the Centre for Addiction and Mental Health (CAMH) in Toronto, Ontario, Canada.

What is the background to your study?

People affected by bipolar disorder (BD) often report reduced neurocognitive performance across many domains, such as sustained attention, memory, or executive function. This is the case for both adults and young people with the condition. Individuals with BD also report subjective experience of mental slowing or dulling and often attribute this reduced neurocognition to their medication1, 2. This contributes to suboptimal adherence, which in turn raises the risk of recurrence, hospitalization, and suicide attempts, and decreases the likelihood of achieving remission and recovery3. Lithium and second-generation antipsychotics (SGA) are first-line antimanic medications for BD, and have been associated with reduced neurocognitive performance in adults with BD, across multiple domains such as attention, processing speed, affective processing and executive functions1,4-9. Nonetheless, there are also studies reporting no significant association of these medications with neurocognition, and studies reporting beneficial effects on certain neurocognitive domains10-16. However, it remains inconclusive whether these medications are associated with reduced neurocognitive performance in youths with BD. The aim of this study was to examine the association of lithium and SGA with neurocognition in young people with bipolar disorder.

Which CANTABTM tasks did you use?

This cross-sectional study included 91 young people, aged 13-20, diagnosed with BD. Participants completed four CANTABTM tests, Intra/Extra Dimensional Set-Shifting (IED), Rapid Visual Information Processing (RVP), Stockings of Cambridge (SOC), and Affective Go/No-Go (AGN). We used these tests to examine set-shifting/flexibility of attention, sustained attention, spatial planning, and information processing biases, respectively, as these domains have been previously implicated in BD among youth and adults17-19. Additionally, global cognition was measured by a global composite score and a g factor that was calculated by combining selected measures from the aforementioned tests.

What were your findings?

Our data show that SGA and lithium use are not significantly associated with neurocognitive decrements in young people with BD. These results may help patients, parents, and healthcare professionals. Specifically, we hope that our findings may help to improve messaging around the side effects of and adherence to these medications, in turn reducing the stigma towards them and improving clinical outcomes of youth BD patients.

Why did you choose CANTABTM for your study?

We chose CANTABTM because it is supported by a substantial body of literature. Also, its automated and user-friendly design provides advantages especially when working with youth, who are accustomed to the computer interface and find it engaging.

What are your next steps?

To build on our findings, future studies that investigate the duration of treatment, serum drug levels and adherence to treatment in relation to effects on neurocognition would be informative. In addition, future randomized controlled clinical trials will assist in understanding the effects of psychotropic medication use on neurocognitive performance in young people with BD.

Read the full paper: https://pubmed.ncbi.nlm.nih.gov/35085001/

References 

1. Pachet, A. K. & Wisniewski, A. M. The effects of lithium on cognition: an updated review. Psychopharmacology (Berl.) 170, 225–234 (2003).
2. Gitlin, M. Lithium side effects and toxicity: prevalence and management strategies. Int. J. Bipolar Disord. 4, 27 (2016).
3. Jawad, I., Watson, S., Haddad, P. M., Talbot, P. S. & McAllister-Williams, R. H. Medication nonadherence in bipolar disorder: a narrative review. Ther. Adv. Psychopharmacol. 8, 349–363 (2018).
4. Holmes, M. K. et al. A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression. Bipolar Disord. 10, 806–815 (2008).
5. Wingo, A. P., Wingo, T. S., Harvey, P. D. & Baldessarini, R. J. Effects of lithium on cognitive performance: a meta-analysis. J. Clin. Psychiatry 70, 1588–1597 (2009).
6. Malhi, G. S. et al. The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder. Bipolar Disord. 18, 102–115 (2016).
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8. Jamrozinski, K., Gruber, O., Kemmer, C., Falkai, P. & Scherk, H. Neurocognitive functions in euthymic bipolar patients. Acta Psychiatr. Scand. 119, 365–374 (2009).
9. Torrent, C. et al. Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients. Int. Clin. Psychopharmacol. 26, e90–e91 (2011).
10. Bourne, C. et al. Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis. Acta Psychiatr. Scand. 128, 149–162 (2013).
11. Daglas, R. et al. A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study. Eur. Psychiatry 31, 20–28 (2016).
12. Burdick, K. E. et al. The association between lithium use and neurocognitive performance in patients with bipolar disorder. Neuropsychopharmacology 45, 1743–1749 (2020).
13. Duffy, A., Milin, R. & Grof, P. Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine. BMC Psychiatry 9, 4 (2009).
14. Henin, A. et al. Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth? J. Clin. Psychiatry 70, 1178–1185 (2009).
15. Streicher, J. V. et al. A Preliminary Study of the Effects of Treatment with Lithium Versus Quetiapine on Attention of Adolescents with Bipolar Disorder. J. Child Adolesc. Psychopharmacol. 30, 465–469 (2020).
16. Wang, L.-J. et al. Neurocognitive effects of aripiprazole in adolescents and young adults with bipolar disorder. Nord. J. Psychiatry 66, 276–282 (2012).
17. Fountoulakis, K. N. Neurocognitive impairment and evidence-based treatment options in Bipolar disorder. Ann. Gen. Psychiatry 19, 54 (2020).
18. Elias, L. R. et al. Cognitive impairment in euthymic pediatric bipolar disorder: A systematic review and meta-analysis. J. Am. Acad. Child Adolesc. Psychiatry 56, 286–296 (2017).
19. Miskowiak, K. W. et al. Assessing and addressing cognitive impairment in bipolar disorder: the International Society for Bipolar Disorders Targeting Cognition Task Force recommendations for clinicians. Bipolar Disord. 20, 184–194 (2018).

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Author:

Xinyue (Joyce) Jiang

Centre for Addiction and Mental Health, Toronto

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