REMİSYONDA BİPOLAR BOZUKLUKTA BİLİŞSEL İŞLEVLER

Tugay Elik

Turgutlu Devlet Hastanesi, Ruh Sağlığı ve Hastalıkları Kliniği, Manisa, Türkiye

Elik T. Remisyonda Bipolar Bozuklukta Bilişsel İşlevler. Aydemir Ö, Esen Danacı A, editörler. Psikiyatrik Bozukluklar ve Bilişsel İşlevler. 1. Baskı. Ankara: Türkiye Klinikleri; 2025. p.75-85.

ÖZET

Bipolar bozukluk, yalnızca duygudurum değişiklikleriyle değil, aynı zamanda bilişsel işlevlerde kalıcı bozulmalarla da karakterize edilen bir hastalıktır. Depresyon ve mani dönemleri arasında görülen remisyon sürecinde dahi, yürütücü işlevler, dikkat, işlem hızı ve bellek gibi bilişsel alanlarda belirgin zorluklar yaşanmaktadır. Araştırmalar, bu bozulmaların hastaların sosyal ve mesleki işlevselliği üzerinde önemli etkiler yarattığını göstermektedir.

Meta-analizler, ötimik dönemdeki hastalarda dahi bilişsel işlevlerin sağlıklı bireylere kıyasla anlamlı ölçüde zayıfladığını ortaya koymaktadır. İlk epizod sonrası bozulmaların kalıcı olabileceği, özellikle çalışma belleği ve bilişsel esneklik gibi alanlarda belirgin kayıpların olduğu saptanmıştır. Ayrıca, bipolar bozukluğu olan bireylerin birinci derece akrabalarında da belirli düzeyde bilişsel bozuklukların gözlemlenmesi, hastalığın nörobiyolojik temellerine işaret etmektedir.

Bilişsel bozulmanın şiddeti; yaş, eğitim düzeyi, hastalık süresi ve çocukluk çağı travmaları gibi faktörlerden etkilenmektedir. İlaç tedavisinin etkileri ise karmaşıktır; bazı antipsikotiklerin bilişsel performansı olumsuz etkileyebileceği, ancak lityumun nöroprotektif etkileri olabileceği öne sürülmektedir.

Son olarak, baskın polarite kavramının bilişsel bozukluklarla ilişkili olabileceği belirtilmektedir. Özellikle manik baskın polariteye sahip hastalarda daha belirgin bilişsel kayıplar gözlemlenmiştir. Genel olarak, bipolar bozuklukta bilişsel işlevler hastalığın tüm evrelerinde etkilenmekte ve bireylerin günlük yaşam kalitesini belirleyen önemli bir faktör olarak öne çıkmaktadır.

Anahtar Kelimeler: Remisyonda bipolar bozukluk; Bilişsel işlevler; Yürütücü işlevler; Sözel bellek

Referanslar

  1. Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241-251. [Crossref]  [PubMed]  [PMC]
  2. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [published correction appears in Lancet. 2019 Jun 22;393(10190):e44.5.]. Lancet. 2018;392(10159):1789-1858. [Crossref]  [PubMed]
  3. Malhi GS, Ivanovski B, Hadzi-Pavlovic D, Mitchell PB, Vieta E, Sachdev P. Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia. Bipolar Disord. 2007;9(1-2):114-125. [Crossref]  [PubMed]
  4. Bulbena A, Berrios GE. Cognitive function in the affective disorders: a prospective study. Psychopathology. 1993;26(1):6-12. [Crossref]  [PubMed]
  5. Baune BT, Malhi GS. A review on the impact of cognitive dysfunction on social, occupational, and general functional outcomes in bipolar disorder. Bipolar Disord. 2015;17 Suppl 2:41-55. [Crossref]  [PubMed]
  6. Tse S, Chan S, Ng KL, Yatham LN. Meta-analysis of predictors of favorable employment outcomes among individuals with bipolar disorder. Bipolar Disord. 2014;16(3):217-229. [Crossref]  [PubMed]
  7. Mann-Wrobel MC, Carreno JT, Dickinson D. Meta-analysis of neuropsychological functioning in euthymic bipolar disorder: an update and investigation of moderator variables. Bipolar Disord. 2011;13(4):334-342. [Crossref]  [PubMed]
  8. Robinson LJ, Thompson JM, Gallagher P, Goswami U, Young AH, Ferrier IN, et al. Ameta-analysis of cognitive deficits in euthymic patients with bipolar disorder. J Affect Disord. 2006;93(1-3):105-115. [Crossref]  [PubMed]
  9. Torres IJ, Boudreau VG, Yatham LN. Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis. Acta Psychiatr Scand Suppl. 2007;(434):17-26. [Crossref]  [PubMed]
  10. Kurtz MM, Gerraty RT. A meta-analytic investigation of neurocognitive deficits in bipolar illness: profile and effects of clinical state. Neuropsychology. 2009;23(5):551-562. [Crossref]  [PubMed]  [PMC]
  11. Arts B, Jabben N, Krabbendam L, van Os J. Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives [published correction appears in Psychol Med. 2009 Mar;39(3):525]. Psychol Med. 2008;38(6):771-785. [Crossref]  [PubMed]
  12. Cotrena C, Damiani Branco L, Ponsoni A, Samamé C, Milman Shansis F, Paz Fonseca R. Executive functions and memory in bipolar disorders I and II: new insights from meta-analytic results. Acta Psychiatr Scand. 2020;141(2):110-130. [Crossref]  [PubMed]
  13. Keramatian K, Torres IJ, Yatham LN. Neurocognitive functioning in bipolar disorder: What we know and what we don’t. Dialogues Clin Neurosci. 2022;23(1):29-38. Published 2022 Jun 1. [Crossref]  [PubMed]  [PMC]
  14. Szmulewicz A, Valerio MP, Martino DJ. Longitudinal analysis of cognitive performances in recent-onset and late-life Bipolar Disorder: A systematic review and meta-analysis. Bipolar Disord. 2020;22(1):28-37. [Crossref]  [PubMed]
  15. Bora E, Özerdem A. Meta-analysis of longitudinal studies of cognition in bipolar disorder: comparison with healthy controls and schizophrenia. Psychol Med. 2017;47(16):27532766. [Crossref]  [PubMed]
  16. Cardoso T, Bauer IE, Meyer TD, Kapczinski F, Soares JC. Neuroprogression and Cognitive Functioning in Bipolar Disorder: A Systematic Review. Curr Psychiatry Rep. 2015;17(9):75. [Crossref]  [PubMed]
  17. Samamé C, Martino DJ, Strejilevich SA. Longitudinal course of cognitive deficits in bipolar disorder: a meta-analytic study. J Affect Disord. 2014;164:130-138. [Crossref]  [PubMed]
  18. Cullen B, Ward J, Graham NA, Deary IJ, Pell JP, Smith DJ et al. Prevalence and correlates of cognitive impairment in euthymic adults with bipolar disorder: A systematic review. J Affect Disord. 2016;205:165-181. [Crossref]  [PubMed]
  19. Burdick KE, Russo M, Frangou S, Mahon K, Braga RJ, Shanahan M, et al. Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications. Psychol Med. 2014;44(14):3083-3096. [Crossref]  [PubMed]  [PMC]
  20. Jensen JH, Knorr U, Vinberg M, Kessing LV, Miskowiak KW. Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder: Associations with functional abilities. J Affect Disord. 2016;205:378-386. [Crossref]  [PubMed]
  21. Jiménez E, Solé B, Arias B, Varo C, Reinares M, Bonnín CDM, et al. Impact of childhood trauma on cognitive profile in bipolar disorder. Bipolar Disord. 2017;19(5):363-374. [Crossref]  [PubMed]
  22. Russo M, Van Rheenen TE, Shanahan M, Mahon K, Perez-Rodriguez MM, Cuesta-Diaz A, et al. Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings. Psychol Med. 2017;47(16):2892-2905. [Crossref]  [PubMed]  [PMC]
  23. Solé B, Jiménez E, Torrent C, Del Mar Bonnin C, Torres I, Reinares M, et al. Cognitive variability in bipolar II disorder: who is cognitively impaired and who is preserved. Bipolar Disord. 2016;18(3):288-299. [Crossref]  [PubMed]
  24. Léda-Rêgo G, Bezerra-Filho S, Miranda-Scippa Â. Functioning in euthymic patients with bipolar disorder: A systematic review and meta-analysis using the Functioning Assessment Short Test. Bipolar Disord. 2020;22(6):569-581. [Crossref]  [PubMed]
  25. Kaya E, Aydemir O, Selcuki D. Residual symptoms in bipolar disorder: the effect of the last episode after remission. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(7):1387-1392. [Crossref]  [PubMed]
  26. Daglas R, Yücel M, Cotton S, Allott K, Hetrick S, Berk M. Cognitive impairment in first-episode mania: a systematic review of the evidence in the acute and remission phases of the illness. Int J Bipolar Disord. 2015;3:9. Published 2015 Apr 25. [Crossref]  [PubMed]  [PMC]
  27. Lee RS, Hermens DF, Scott J, Redoblado-Hodge MA, Naismith SL, Lagopoulos J, et al. A meta-analysis of neuropsychological functioning in first-episode bipolar disorders. J Psychiatr Res. 2014;57:1-11. [Crossref]  [PubMed]
  28. Bora E, Pantelis C. Meta-analysis of Cognitive Impairment in First-Episode Bipolar Disorder: Comparison With First-Episode Schizophrenia and Healthy Controls. Schizophr Bull. 2015;41(5):1095-1104. [Crossref]  [PubMed]  [PMC]
  29. Elias LR, Miskowiak KW, Vale AM, Köhler CA, Kjærstad HL, Stubbs B, et al. Cognitive Impairment in Euthymic Pediatric Bipolar Disorder: A Systematic Review and Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2017;56(4):286-296. [Crossref]  [PubMed]
  30. Martino DJ, Samamé C, Ibañez A, Strejilevich SA. Neurocognitive functioning in the premorbid stage and in the first episode of bipolar disorder: a systematic review. Psychiatry Res. 2015;226(1):23-30. [Crossref]  [PubMed]
  31. Koenen KC, Moffitt TE, Roberts AL, Martin LT, Kubzansky L, Harrington H, et al. Childhood IQ and adult mental disorders: a test of the cognitive reserve hypothesis. Am J Psychiatry. 2009;166(1):50-57. [Crossref]  [PubMed]  [PMC]
  32. Meyer SE, Carlson GA, Wiggs EA, Martinez PE, Ronsaville DS, Klimes-Dougan B, et al. A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder. Dev Psychopathol. 2004;16(2):461-476. [Crossref]  [PubMed]
  33. Ratheesh A, Lin A, Nelson B, Wood SJ, Brewer W, Betts J et al. Neurocognitive functioning in the prodrome of mania-an exploratory study. J Affect Disord. 2013;147(1-3):441-445. [Crossref]  [PubMed]
  34. Bora E, Yucel M, Pantelis C. Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord. 2009;113(1-2):1-20. [Crossref]  [PubMed]
  35. Cardenas SA, Kassem L, Brotman MA, Leibenluft E, McMahon FJ. Neurocognitive functioning in euthymic patients with bipolar disorder and unaffected relatives: A review of the literature. Neurosci Biobehav Rev. 2016;69:193-215. [Crossref]  [PubMed]  [PMC]
  36. Bora E. Neurocognitive features in clinical subgroups of bipolar disorder: A meta-analysis. J Affect Disord. 2018;229:125-134. [Crossref]  [PubMed]
  37. Dickinson T, Becerra R, Coombes J. Executive functioning deficits among adults with Bipolar Disorder (types I and II): A systematic review and meta-analysis. J Affect Disord. 2017;218:407-427. [Crossref]  [PubMed]
  38. Hsiao YL, Wu YS, Wu JY, Hsu MH, Chen HC, Lee SY, et al. Neuropsychological functions in patients with bipolar I and bipolar II disorder. Bipolar Disord. 2009;11(5):547-554. [Crossref]  [PubMed]
  39. Simonsen C, Sundet K, Vaskinn A, Birkenaes AB, Engh JA, Hansen CF, et al. Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction. Bipolar Disord. 2008;10(2):245-255. [Crossref]  [PubMed]
  40. Torrent C, Martínez-Arán A, Daban C, Sánchez-Moreno J, Comes M, Goikolea JM, et al. Cognitive impairment in bipolar II disorder [published correction appears in Br J Psychiatry. 2006 Dec;189:569]. Br J Psychiatry. 2006;189:254-259. [Crossref]  [PubMed]
  41. Martino DJ, Igoa A, Marengo E, Scápola M, Strejilevich SA. Neurocognitive impairments and their relationship with psychosocial functioning in euthymic bipolar II disorder. J Nerv Ment Dis. 2011;199(7):459-464. [Crossref]  [PubMed]
  42. Dittmann S, Hennig-Fast K, Gerber S, Seemüller F, Riedel M, Emanuel Severus W, et al. Cognitive functioning in euthymic bipolar I and bipolar II patients. Bipolar Disord. 2008;10(8):877-887. [Crossref]  [PubMed]
  43. Dauvermann MR, Donohoe G. The role of childhood trauma in cognitive performance in schizophrenia and bipolar disorder A systematic review. Schizophr Res Cogn. 2018;16:1-11. Published 2018 Dec 11. [Crossref]  [PubMed]  [PMC]
  44. Bücker J, Kozicky J, Torres IJ, Kauer-Sant’anna M, Silveira LE, Bond DJ et al. The impact of childhood trauma on cognitive functioning in patients recently recovered from a first manic episode: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM). J Affect Disord. 2013;148(2-3):424-430. [Crossref]  [PubMed]
  45. Poletti S, Aggio V, Brioschi S, Dallaspezia S, Colombo C, Benedetti F. Multidimensional cognitive impairment in unipolar and bipolar depression and the moderator effect of adverse childhood experiences. Psychiatry Clin Neurosci. 2017;71(5):309-317. [Crossref]  [PubMed]
  46. Aas M, Steen NE, Agartz I, Aminoff SR, Lorentzen S, Sundet K, et al. Is cognitive impairment following early life stress in severe mental disorders based on specific or general cognitive functioning?. Psychiatry Res. 2012;198(3):495-500. [Crossref]  [PubMed]
  47. Marshall DF, Passarotti AM, Ryan KA, Kamali M, Saunders EF, Pester B, et al. Deficient inhibitory control as an outcome of childhood trauma. Psychiatry Res. 2016;235:7-12. [Crossref]  [PubMed]  [PMC]
  48. Bourne C, Aydemir Ö, Balanzá-Martínez V, Bora E, Brissos S, Cavanagh JT, et al. Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis. Acta Psychiatr Scand. 2013;128(3):149-162. [Crossref]  [PubMed]
  49. Xu N, Huggon B, Saunders KEA. Cognitive Impairment in Patients with Bipolar Disorder: Impact of Pharmacological Treatment. CNS Drugs. 2020;34(1):29-46. [Crossref]  [PubMed]
  50. Yatham LN, Mackala S, Basivireddy J, Ahn S, Walji N, Hu C, et al. Lurasidone versus treatment as usual for cognitive impairment in euthymic patients with bipolar I disorder: a randomised, open-label, pilot study [published correction appears in Lancet Psychiatry. 2017 Mar;4(3):185. [Crossref]  [PubMed]
  51. Torrent C, Martinez-Arán A, Daban C, Amann B, Balanzá-Martínez V, del Mar Bonnín C, et al. Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients. Compr Psychiatry. 2011;52(6):613-622. [Crossref]  [PubMed]
  52. Paterson A, Parker G. Lithium and cognition in those with bipolar disorder. Int Clin Psychopharmacol. 2017;32(2):57-62. [Crossref]  [PubMed]
  53. Wingo AP, Wingo TS, Harvey PD, Baldessarini RJ. Effects of lithium on cognitive performance: a meta-analysis. J Clin Psychiatry. 2009;70(11):1588-1597. [Crossref]  [PubMed]
  54. Mora E, Portella MJ, Forcada I, Vieta E, Mur M. A preliminary longitudinal study on the cognitive and functional outcome of bipolar excellent lithium responders. Compr Psychiatry. 2016;71:25-32. [Crossref]  [PubMed]
  55. Mur M, Portella MJ, Martínez-Arán A, Pifarré J, Vieta E. Long-term stability of cognitive impairment in bipolar disorder: a 2-year follow-up study of lithium-treated euthymic bipolar patients. J Clin Psychiatry. 2008;69(5):712-719. [Crossref]  [PubMed]
  56. Mur M, Portella MJ, Martínez-Arán A, Pifarré J, Vieta E. Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval. Acta Psychiatr Scand. 2008;118(5):373-381. [Crossref]  [PubMed]
  57. Joffe RT, MacDonald C, Kutcher SP. Lack of differential cognitive effects of lithium and carbamazepine in bipolar affective disorder. J Clin Psychopharmacol. 1988;8(6):425-428. [Crossref]  [PubMed]
  58. López-Jaramillo C, Lopera-Vásquez J, Ospina-Duque J, García J, Gallo A, Cortez V, et al. Lithium treatment effects on the neuropsychological functioning of patients with bipolar I disorder. J Clin Psychiatry. 2010;71(8):1055-1060.
  59. Garnham J, Munro A, Slaney C, Macdougall M, Passmore M, Duffy A, et al. Prophylactic treatment response in bipolar disorder: results of a naturalistic observa tion study. J Affect Disord. 2007;104(1-3):185-190. [Crossref]  [PubMed]
  60. Rybakowski JK, Suwalska A. Excellent lithium responders have normal cognitive functions and plasma BDNF levels. Int J Neuropsychopharmacol. 2010;13(5):617-622. [Crossref]  [PubMed]
  61. Carvalho AF, McIntyre RS, Dimelis D, Gonda X, Berk M, Nunes-Neto PR, et al. Predominant polarity as a course specifier for bipolar disorder: a systematic review. J Affect Disord. 2014;163:56-64. [Crossref]  [PubMed]
  62. Belizario GO, Gigante AD, de Almeida Rocca CC, Lafer B. Cognitive impairments and predominant polarity in bipolar disorder: a cross-sectional study. Int J Bipolar Disord. 2017;5(1):15. [Crossref]  [PubMed]  [PMC]
  63. Atay E, Ermiş Ç, Gökbayrak Atay İN, Aydemir Ö, Özmen E. The role of predominant polarity on cognitive dysfunctions in patients with bipolar disorder. Int J Bipolar Disord. 2024;12(1):41. Published 2024 Nov 29. [Crossref]  [PubMed]  [PMC]