Evaluation and Treatment of Cognitive Dysfunctions in Schizophrenia and Bipolar Disorder

Abstract

Cognitive dysfunction is the most important determinant for the recovery in schizophrenia and bipolar disorder. Cognitive dysfunction serves as an endophenotype although it may be a consequence of drug treatments. In schizophrenia starting from the first episode, pronounced cognitive defects such as cognitive flexibility, inhibition, verbal fluency, verbal memory and visual-motor processing are observable. These cognitive defects remain stable in the chronic phase of schizophrenia. On the other hand, cognitive dysfunctions in bipolar disorder patients have a heterogeneous pattern. One group of patients show no evidence of cognitive dysfunction while one group has limited dysfunction (of processing speed, attention, verbal learning and social cognition) and another one has wide spread dysfunctions as seen in schizophrenia. Despite its importance, no satisfactory results have been achieved in the treatment of cognitive dysfunctions in schizophrenia and bipolar disorder. In this article, the evaluation and treatment of the most frequent cognitive dysfunctions of schizophrenia and bipolar disorder are reviewed.

Keywords

• bipolar disorder
• cognitive dysfunction
• cognitive remediation
• schizophrenia
• cognitive evaluation

Şizofreni ve Bipolar Bozuklukta Bilişsel İşlev Bozukluklarının Değerlendirilmesi ve Tedavisi

Öz

Bilişsel bozukluklar hem şizofreni hem de bipolar bozukluk seyrinde iyileşme ile en yakından etkili hastalık bileşenidir. Bilişsel işlevlerdeki bozulma hem bir endofenotip özelliği göstermekte hem de tedavi sürecine bağlı olarak da ortaya çıkabilmektedir. Şizofrenide ilk ataktan başlayarak bilişsel esneklik, baskılama, sözel akıcılık, sözel bellek ve görsel-motor işleme alanlarında bozulmalar gözlenmekte ve kronik hastalık evresinde bu bulgular değişmemektedir. Öte yandan bipolar bozukluk hastaları ise bilişsel işlevler yönünden birbirinden çok farklı özellikler göstermektedir. Bir grup hastada hiçbir bilişsel bozukluk saptanmazken; diğer bir grupta sınırlı alanlarda (işlem hızı, dikkat, sözel öğrenme ve sosyal biliş) bozukluk gözlenmekte; üçüncü bir grupta ise şizofrenidekine benzer yaygın ve ağır bilişsel bozukluklar izlenmektedir. Bu hastalıklarda oynadığı önemli role karşın bilişsel işlevlerin tedavisinde ne yazık ki istenilen sonuçlara ulaşılamamıştır. Bu gözden geçirme yazısında şizofreni ve bipolar bozuklukta görülen bilişsel işlev bozuklukları ve bunların tanınmasına yönelik testler, bilişsel rehabilitasyon için yapılabilecekler ve henüz gelişme aşamasındaki bilişsel işlev farmakoterapisine yer verilecektir.

Anahtar Kelimeler

• şizofreni
• bipolar bozukluk
• bilişsel onarım
• bilişsel değerlendirme
• bilişsel işlev bozukluğu

Kaynakça

1. Agnew-Blais J, Seidman LJ (2013) Neurocognition in youth and young adults under age 30 at familial risk for schizophrenia: A quantitative and qualitative review. Cogn Neuropsychiatry, 18:44-82.
2. APA (2013) Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) Washington DC, American Psychiatric Association.
3. Bakker G, Vingerhoets C, Bloemen OJN, Sahakian BJ, Booij J, Caan MWA, van Amelsvoort TAJM (2020) The muscarinic M1 receptor modulates associative learning and memory in psychotic disorders. NeuroImage Clin, 27:102278.
4. Baldez DP, Biazus TB, Rabelo-da-Ponte FD, Nogaro GP, Martins DS, Kunz M et al. (2021) The effect of antipsychotics on the cognitive performance of individuals with psychotic disorders: Network meta-analyses of randomized controlled trials. Neurosci Biobehav Rev, 126:265-275.
5. Bergemann N, Parzer P, Jaggy S, Auler B, Mundt C, Maier-Braunleder S (2008) Estrogen and comprehension of metaphoric speech in women suffering from schizophrenia: Results of a double-blind, placebo-controlled trial. Schizophr Bull, 34:1172-1181.
6. Bora E (2016) Differences in cognitive impairment between schizophrenia and bipolar disorder: Considering the role of heterogeneity. Psychiatry Clin Neurosci, 70:424-433.
7. Bora E (2018) Neurocognitive features in clinical subgroups of bipolar disorder: A meta-analysis. J Affect Disord, 229:125-134.
8. Bora E, Özerdem A (2017) Meta-analysis of longitudinal studies of cognition in bipolar disorder: Comparison with healthy controls and schizophrenia. Psychol Med, 47:2753-2766.

9. Bora E, Özerdem A (2017) Social cognition in first-degree relatives of patients with bipolar disorder: A meta-analysis. Eur Neuropsychopharmacol, 27:293-300.
10. Bora E, Yucel M, Pantelis C (2009) Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord, 113:1-20.
11. Bowie CR, Bell MD, Fiszdon JM, Johannesen JK, Lindenmayer JP, McGurk SR et al. (2020) Cognitive remediation for schizophrenia: An expert working group white paper on core techniques. Schizophr Res, 215:49-53.
12. Bulbena A, Berrios GE (1993) Cognitive function in the affective disorders: A prospective study. Psychopathology, 26:6-12.
13. Burdick KE, Russo M, Frangou S, Mahon K, Braga RJ, Shanahan M et al. (2014) Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: Clinical implications. Psychol Med, 44:3083-3096.
14. Cotrena C, Damiani Branco L, Ponsoni A, Samamé C, Milman Shansis F, Paz Fonseca R (2020) Executive functions and memory in bipolar disorders I and II: New insights from meta-analytic results. Acta Psychiatr Scand, 141:110-130.
15. Douglas KM, Gallagher P, Robinson LJ, Carter JD, McIntosh VVW, Frampton CMA et al.. (2018) Prevalence of cognitive impairment in major depression and bipolar disorder. Bipolar Disord, 20:260-274.
16. Eker MC, Altinbaş K (2020) Duygudurum bozukluklarının etiyolojisi. In: Duygudurum Bozuklukları Tanı Ve Tedavisi, (Ed K Altınbaş):15-50. Konya, Bahçıvanlar Basım.
17. Green MF (2006) Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry, 67:3-8.
18. Hoff AL, Sakuma M, Wieneke M, Horon R, Kushner M, DeLisi LE (1999) Longitudinal neuropsychological follow-up study of patients with first-episode schizophrenia. Am J Psychiatry, 156:1336-1341.
19. Husain M, Schott JM (2016) Oxford Textbook of Cognitive Neurology and Dementia. New York: Oxford University Press.
20. Joshi YB, Thomas ML, Braff DL, Green MF, Gur RC, Gur RE et al. (2021) Anticholinergic medication burden-associated cognitive impairment in schizophrenia. Am J Psychiatry, 178:838-847.
21. Kapczinski F, Pfaffenseller B, Dursun SM, Cardoso TA (2021) Clozapine for bipolar disorder: What do we know so far and what next? Bipolar Disord, 23:115-116.
22. Kindler J, Lim CK, Weickert CS, Boerrigter D, Galletly C, Liu D et al. (2020) Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia. Mol Psychiatry, 25:2860-2872.
23. Kloiber S, Rosenblat JD, Husain MI, Ortiz A, Berk M, Quevedo J, Vieta E et al. (2020) Neurodevelopmental pathways in bipolar disorder. Neurosci Biobehav Rev, 112:213-226.
24. Koblan KS, Kent J, Hopkins SC, Krystal JH, Cheng H, Goldman R et al. (2020) A non-D2-receptor-binding drug for the treatment of schizophrenia. N Engl J Med, 382:1497-1506.
25. Koola MM, Looney SW, Hong H, Pillai A, Hou W (2020) Meta-analysis of randomized controlled trials of galantamine in schizophrenia: Significant cognitive enhancement. Psychiatry Res, 291:113285.
26. Kuo CY, Lin CH, Lane HY (2022) Targeting D-amino acid oxidase (DAAO) for the treatment of schizophrenia: Rationale and current status of research. CNS Drugs, 36:1143-1153.
27. Lewandowski KE, Cohen BM, Ongur D (2011) Evolution of neuropsychological dysfunction during the course of schizophrenia and bipolar disorder. Psychol Med, 41:225-241.
28. Li W, Zhou FC, Zhang L, Ng CH, Ungvari GS, Li J et al. (2020) Comparison of cognitive dysfunction between schizophrenia and bipolar disorder patients: A meta-analysis of comparative studies. J Affect Disord, 274:652-661.
29. Lobo MC, Whitehurst TS, Kaar SJ, Howes OD (2022) New and emerging treatments for schizophrenia: A narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Neurosci Biobehav Rev, 132:324-361.
30. MacQueen GM, Memedovich KA (2017) Cognitive dysfunction in major depression and bipolar disorder: Assessment and treatment options. Psychiatry Clin Neurosci, 71:18-27.
31. McKay AP, Tarbuck AF, Shapleske J, McKenna PJ (1995) Neuropsychological function in manic-depressive psychosis, Evidence for persistent deficits in patients with chronic, severe illness. Br J Psychiatry, 167:51-57.
32. Menkes MW, Armstrong K, Blackford JU, Heckers S, Woodward ND (2019) Neuropsychological functioning in early and chronic stages of schizophrenia and psychotic bipolar disorder. Schizophr Res, 206:413-419.
33. Mesholam-Gately RI, Giuliano AJ, Goff KP, Faraone SV, Seidman LJ (2009) Neurocognition in first-episode schizophrenia, A meta-analytic review. Neuropsychology, 23:315-336.
34. Pawełczyk T, Piątkowska-Janko E, Bogorodzki P, Gębski P, Grancow-Grabka M et al. (2018) Omega-3 fatty acid supplementation may prevent loss of gray matter thickness in the left parieto-occipital cortex in first episode schizophrenia, A secondary outcome analysis of the OFFER randomized controlled study. Schizophr Res, 195:168-175.
35. Pitsikas N (2015) The role of nitric oxide donors in schizophrenia, Basic studies and clinical applications. Eur J Pharmacol, 766:106-113.
36. Rapoport JL, Giedd JN, Gogtay N (2012) Neurodevelopmental model of schizophrenia, Update 2012. Mol Psychiatry, 17:1228-1238.
37. Sathyasaikumar KV, Stachowski EK, Wonodi I, Roberts RC, Rassoulpour A, McMahon RP et al. (2011) Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr Bull, 37:1147-1156.
38. Sedler MJ (1994) Foundations of the new nosology. J Med Philos, 19:219-238.
39. Shah AA, Iqbal SZ (2023) Recent advances in psychopharmacology, From bench to bedside novel trends in schizophrenia. J Pers Med, 13:411.
40. Sitskoorn MM, Aleman A, Ebisch SJH, Appels MCM, Kahn RS (2004) Cognitive deficits in relatives of patients with schizophrenia, A meta-analysis. Schizophr Res, 71:285-295.
41. Tschentscher N, Woll CFJ, Tafelmaier JC, Kriesche D, Bucher JC, Engel RR, Karch S (2023) Neurocognitive deficits in first-episode and chronic psychotic disorders, A systematic review from 2009 to 2022. Brain Sci, 13:299.
42. van Gorp W, Altshuler L, Theberge DC, Wilkins J, Dixon W (1998) Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence: A preliminary study. Arch Gen Psychiatry, 55:41-46.
43. Vasconcelos GS, Ximenes NC, de Sousa CNS, Oliveira TQ, Lima LLL, Lucena DF et al. (2015) Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice, Participation of antioxidant, nitrergic and neurotrophic mechanisms. Schizophr Res, 165:163-170.
44. Veselinović T, Neuner I (2022) Progress and pitfalls in developing agents to treat neurocognitive deficits associated with schizophrenia. CNS Drugs, 36:819-858.
45. Vita A, Gaebel W, Mucci A, Sachs G, Barlati S, Giordano GM et al. (2022) European Psychiatric Association guidance on treatment of cognitive impairment in schizophrenia. Eur Psychiatry, 65:e57.
46. Woodberry KA, Giuliano AJ, Seidman LJ (2008) Premorbid IQ in schizophrenia, A meta-analytic review. Am J Psychiatry, 165:579-587.
47. Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P (2011) A meta-analysis of cognitive remediation for schizophrenia, Methodology and effect sizes. Am J Psychiatry, 168:472-485.
48. Yatham LN, Mackala S, Basivireddy J, Ahn S, Walji N, Hu C et al. (2017) Lurasidone versus treatment as usual for cognitive impairment in euthymic patients with bipolar I disorder, A randomised, open-label, pilot study. Lancet Psychiatry, 4:208-217.