Neurocognitive Deficits in Euthymic Bipolar Patients

Abstract

Neurocognitive deficits detected in bipolar patients have a negative influence on clinical course and severity. We reviewed studies on neurocognitive deficits in euthymic bipolar subjects and their possible neuroanatomical correlates. We also examined studies suggesting deficits seen in euthymic patients may be endophenotypes of the disorder. Results of the studies in euthymic patients and their healthy relatives indicate that have cognitive dysfunctions especially of verbal memory, learning and executive domains, which were found to be related to prefrontal cortex and temporo-limbic circuitry. Longitudinal studies investigating heritability of cognitive impairment in bipolar disorder and its relation with brain connectivity and epigenetic mechanisms are needed. Keywords: Bipolar disorder, neurocognitive deficit, endophenotype

Keywords

• Bipolar disorder, neurocognitive deficits, endophenotype

Ötimik Bipolar Hastalarda Nörobilişsel Defisitler

Öz

Nörobilişsel defisitlerin bipolar bozukluğun seyri ve ciddiyeti üzerinde belirle-yici olduğu bilinmektedir. Bu derlemede ötimik bipolar hastalarda nörobilişsel defisit varlığını, bu defisitlerle bipolar hastalarda saptanan nöroanatomik lezyonların ilişkisi ve bu hastalarda saptanan bazı defisitlerin bir endofenotip olabileceği ile ilgili çalışmaları gözden geçirilmiştir. Çalışmalar ötimik hastalarda ve sağlıklı aile bireylerinde prefrontal korteks, temporo-limbik döngü ile ilişkili bulunan sözel bellek, öğrenme ve yürütücü fonksiyon alanlarında defisit gösterdiklerini teyit etmiştir. Ötimik hastalarda saptanan bilişsel defisitlerin genetik temellerini, bipolar hastalarda nöroanatomik tutu-lumla olan ilişkisini ve epigenetik mekanizmaların hastalık sürecine olası etkilerini araştırmaya yönelik çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Bipolar bozukluk, nörobilişsel defisit, endofenotip

References

1. Martino DJ, Marengo E, Igoa A, Scápola M, Ais ED, Perinot L et al. Neurocognitive and symptomatic predictors of functional outcome in bipolar disorders: A prospective 1 year follow-up study. J Affect Disord 2009; 116:37-42.
2. Zubieta JK, Huguelet P, O’Neil RL, Giordani BJ. Cognitive function in euthymic bipolar I disorder. Psychiatry Res 2001; 102:9-20.
3. Martinez-Aran A, Vieta E, Reinares M, Colom F, Torrent C, Sanchez-Moreno J et al. Cognitive function across manic or hypomanic, depressed and euthymic states in bipolar disorder. Am J Psychiatry 2004; 161:262-270.
4. van Gorp WG, Altshuler L, Theberge DC, Wilkins J, Dixon W. Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence: a preliminary study. Arch Gen Psychiatry 1998; 55:41-46.
5. Thompson JM, Gallagher P, Hughes JH, Watson S, Gray JM, Ferrier IN et al. Neurocognitive impairment in euthymic patients with bipolar affective disorder. Br J Psychiatry 2005; 186:32-40.
6. Arts B, Jabben N, Krabbendam L, van Os J. Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychol Med 2008; 38:771-785.
7. Lloyd AJ, Moore PB, Cousins DA, Thompson JM, McAllister VL, Hughes JH et al. White matter lesions in euthymic patients with bipolar disorder. Acta Psychiatr Scand 2009: 120:481-491.
8. Bonnín CM, Martínez-Arán A, Torrent C, Pacchiarotti I, Rosa AR, Franco C et al. Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term, follow-up study. J Affect Disord 2010; 121:156-160.

9. Martino DJ, Strejilevich SA, Scápola M, Igoa A, Marengo E, Ais ED et al. Heterogeneity in cognitive functioning among patientswith bipolar disorder. J Affect Disord 2008; 109:149-156.
10. Robinson LJ, Ferrier IN. Evolution of cognitive impairment in bipolar disorder: a systematic review of cross sectional evidence. Bipolar Disord 2006; 8(suppl 2):103- 116.
11. Depp CA, Moore DJ, Sitzer D, Palmer BW, Eyler LT, Roesch S et al. Neurocognitive impairment in middle-aged and older adults with bipolar disorder: Comparison to schizophrenia and normal comparison subjects. J Affect Disord 2007; 101:201-209.
12. Torrent C, Martinez-Aran A, Daban C, Sanchez-Moreno J, Comes M, Goikolea JM et al. Cognitive impairment in bipolar II disorder. Br J Psychiatry 2006; 189:254- 259.
13. Montag C, Ehrlich A, Neuhaus K, Dziobek I, Heekeren HR, Heinz A et al. Theory of mind impairments in euthymic bipolar patients. J Affect Disord 2010; 123:264- 269.
14. Amado-Boccara I, Gougoulis N, Poirier Littre MF, Galinowski A, Loo H. Effects of antidepressants on cognitive functions: a review. Neurosci Biobehav Rev 1995; 19:479-493.
15. Goswami U, Sharma A, Varma A, Gulrajani C, Ferrier IN, Young AH et al. The neurocognitive performance of drug-free and medicated euthymic bipolar patients do not differ. Acta Psychiatr Scand 2009: 120:456-463.
16. Berk M. Neuroprogression: pathways to progressive brain changes in bipolar disorder. Int J Neuropsychopharmacol 2009; 12:441-445.
17. Frey BN, Zunta-Soares GB, Caetano SC, Nicoletti MA, Hatch JP, Brambilla P et al. Illness duration and total brain gray matter in bipolar disorder: Evidence for neurodegeneration? Eur Neuropsychopharmacol 2008; 18:717-722.
18. Strakowski SM, Adler CM, Holland SK, Mills N, DelBello MP. A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology 2004; 29:1734-1740.
19. Squire LR, Slater PC. Electroconvulsive therapy and complaints of memory dysfunction: a prospective three-year follow-up study. Br J Psychiatry 1983; 142:1-8.
20. Watson S, Gallagher P, Ritchie JC, Ferrier IN, Young AH. Hypothalamic-pituitary- adrenal axis function in patients with bipolar disorder. Br J Psychiatry 2004; 184:496-502.
21. Satz P. Brain reserve capacity on symptom onset after brain injury: a formulation and review of evidence for threshold theory. Neuropsychology 1993; 7:73-295.
22. Barnett JH, Salmond CH, Jones PB, Sahakian BJ. Cognitive reserve in neuropsychiatry. Psychol Med 2006; 36:1053-1064.
23. Ferrier IN, Stanton BR, Kelly TP, Scott J. Neuropsychological function in euthymic patients with bipolar disorder. Br J Psychiatry 1999; 175:246-251.
24. Rubinstein JS, Michael A, Paykel ES, Sahakian BJ. Cognitive impairment in remission in bipolar affective disorder. Psychol Med 2000; 30:1025-1036.
25. Cavanagh JT, Van Beck M, Muir W, Blackwood DH. Case-control study of neurocognitive function in euthymic patients with bipolar disorder: an association with mania. Br J Psychiatry 2002; 180:320-326.
26. Clark L, Iversen SD, Goodwin GM. Sustained attention deficit in bipolar disorder. Br J Psychiatry 2002; 180:313-319.
27. Lesser IM, Boone KB, Mehringer CM, Wohl MA, Miller BL, Berman NG. Cognition and white matter hiperintensities in older depressed patients. Am J Psychiatry 1996; 153:1280-1287.
28. Videbech P. MRI findings in patients with affective disorder: a meta-analysis. Acta Psychiatr Scand 1997; 96:157-168.
29. Bora E, Fornito A, Yücel M, Pantelis C. Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry 2010; 67:1097-1105.
30. Houenou J, Frommberger J, Carde S, Glasbrenner M, Diener C, Leboyer M et al. Neuroimaging-based markers of bipolar disorder: evidence from two meta-analyses. J Affect Disord 2011; 132:344-355.
31. Bruno SD, Barker GJ, Cercignani M, Symms M, Ron MA. A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry. Brain 2004; 127: 2433-2440.
32. Strakowski SM, DelBello MP, Zimmerman ME, Getz GE, Mills NP, Ret J et al. Ventricular and periventricular structural volumes in first- versus multipleepisode bipolar disorder. Am J Psychiatry 2002; 159:1841-1847.
33. Strakowski SM, Delbello MP, Adler CM. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry 2005; 10:105-116.
34. Swayze VW, Andreasen NC, Alliger RJ, Yuh WT, Ehrhardt JC. Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study. Biol Psychiatry 1992; 3:221-240.
35. Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord 2001; 3:106-150.
36. Dupont RM, Jernigan TL, Heindel W, Butters N, Shafer K, Wilson T et al. Magnetic resonance imaging and mood disorders. Localisation of white matter and other abnormalities. Arch Gen Psychiatry 1995; 52:747-755.
37. Robinson LJ, Thompson JM, Gallagher P, Goswami U, Young AH, Ferrier IN et al. A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. J Affect Disord 2006; 93:105-115.
38. Lopez-Larson MP, DelBello MP, Zimmerman ME, Schwiers ML, Strakowski SM. Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry 2002; 52:93-100.
39. Curtis VA, Thompson JM, Seal ML, Monks PJ, Lloyd AJ, Harrison L et al. The nature of abnormal language processing in euthymic bipolar I disorder: evidence for a relationship between task demand and prefrontal function. Bipolar Disord 2007: 9:358-369.
40. El-Badri SM, Cousins DA, Parker S, Ashton HC, McAllister VL, Ferrier IN et al. Magnetic resonance imaging abnormalities in young euthymic patients with bipolar affective disorder. Br J Psychiatry 2006; 189:81-88.
41. Ferrier IN, Thompson JM. Cognitive impairment in bipolar affective disorder: implications for the bipolar diathesis. Br J Psychiatry 2002; 180:293-295.
42. Christensen MV, Kyvik KO, Kessing LV. Cognitive function in unaffected twins discordant for affective disorder. Psychol Med 2006; 36:1119-1129.
43. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160:636-645.
44. Goswami U, Sharma A, Khastigir U, Ferrier IN, Young AH, Gallagher P et al. Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder. Br J Psychiatry 2006; 188:366-373.
45. Bora E, Yucel M, Pante C. Cognitive endophenotypes of bipolar disorder: A metaanalysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord 2009; 113:1-20.
46. Hasler G, Drevets WC, Gould TD, Gottesman II, Manji HK. Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry 2006; 60:93-105.
47. Ayşegül Demirel, Uzm.Dr., Üsküdar Devlet Hastanesi, İstanbul; Ömer Faruk Demirel, Dr., İ.Ü. Cerrahpaşa
48. Tıp Fakültesi Psikiyatri ABD, İstanbul; Muhammed Tayyip Kadak, Uzm. Dr., Yüzüncü Yıl Üniv. Tıp Fak. Çocuk
49. Psikiyatrisi ABD, Van; Alattin Duran, Prof. Dr., İ.Ü. Cerrahpaşa Tıp Fakültesi Psikiyatri ABD, İstanbul