Skip to main content Accessibility help
×
Home

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder

  • C. McCormack (a1), M. J. Green (a1) (a2), J. E. Rowland (a1), G. Roberts (a1), A. Frankland (a1), D. Hadzi-Pavlovic (a1), C. Joslyn (a1), P. Lau (a1), A. Wright (a1), F. Levy (a1), R. K. Lenroot (a1) and P. B. Mitchell (a1) (a2)...

Abstract

Background

Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives.

Method

Neurocognitive and social cognitive ability was examined in 99 young people (age range 16–30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD.

Results

Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs.

Conclusions

Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

Copyright

Corresponding author

*Address for correspondence: M. J. Green, School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia. (Email: melissa.green@unsw.edu.au)

References

Hide All
American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). American Psychiatric Association: Arlington, VA.
Arts, B, Jabben, N, Krabbendam, L, Van Os, J (2008). Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychological Medicine 38, 771786.
Balanza-Martinez, V, Rubio, C, Selva-Vera, G, Martinez-Aran, A, Sanchez-Moreno, J, Salazar-Fraile, J, Vieta, E, Tabares-Seisdedos, R (2008). Neurocognitive endophenotypes (endophenocognitypes) from studies of relatives of bipolar disorder subjects: a systematic review. Neuroscience and Biobehavioral Reviews 32, 14261438.
Berk, M, Hallam, KT, McGorry, PD (2007). The potential utility of a staging model as a course specifier: a bipolar disorder perspective. Journal of Affective Disorders 100, 279281.
Bora, E, Vahip, S, Akdeniz, F, İlerisoy, H, Aldemir, E, Alkan, M (2008). Executive and verbal working memory dysfunction in first-degree relatives of patients with bipolar disorder. Psychiatry Research 61, 318324.
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. Journal of Affective Disorders 113, 120.
Bora, E, Yücel, M, Pantelis, C (2010). Cognitive impairment in affective psychoses: a meta-analysis. Schizophrenia Bulletin 36, 112125.
Brand, JG, Goldberg, TE, Gunawardane, N, Gopin, CB, Powers, RL, Malhotra, AK, Burdick, KE (2012). Emotional bias in unaffected siblings of patients with bipolar I disorder. Journal of Affective Disorders 136, 10531058.
Brotman, MA, Guyer, AE, Lawson, ES, Horsey, SE, Rich, BA, Dickstein, DP, Pine, DS, Leibenluft, E (2008). Facial emotion labeling deficits in children and adolescents at risk for bipolar disorder. American Journal of Psychiatry 165, 385389.
Burdick, KE, Russo, M, Frangou, S, Mahon, K, Braga, RJ, Shanahan, M, Malhotra, AK (2014). Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications. Psychological Medicine 44, 30833096.
Clark, L, Kempton, MJ, Scarna, A, Grasby, PM, Goodwin, GM (2005). Sustained attention-deficit confirmed in euthymic bipolar disorder but not in first-degree relatives of bipolar patients or euthymic unipolar depression. Biological Psychiatry 57, 183187.
Craddock, N, Sklar, P (2013). Genetics of bipolar disorder. Lancet 381, 16541662.
Elliott, R, Ogilvie, A, Rubinsztein, JS, Calderon, G, Dolan, RJ, Sahakian, BJ (2004). Abnormal ventral frontal response during performance of an affective go/no go task in patients with mania. Biological Psychiatry 55, 11631170.
Ferrier, IN, Chowdhury, R, Thompson, JM, Watson, S, Young, AH (2004). Neurocognitive function in unaffected first-degree relatives of patients with bipolar disorder: a preliminary report. Bipolar Disorders 6, 319322.
Fleck, DE, Shear, PK, Zimmerman, ME, Getz, GE, Corey, KB, Jak, A, Lebowitz, BK, Strakowski, SM (2003). Verbal memory in mania: effects of clinical state and task requirements. Bipolar Disorders 5, 375380.
Frangou, S, Haldane, M, Roddy, D, Kumari, V (2005). Evidence for deficit in tasks of ventral, but not dorsal, prefrontal executive function as an endophenotypic marker for bipolar disorder. Biological Psychiatry 58, 838839.
Fries, G, Pfaffenseller, B, Stertz, L, Paz, A, Dargél, A, Kunz, M, Kapczinski, F (2012). Staging and neuroprogression in bipolar disorder. Current Psychiatry Reports 14, 667675.
Geller, B, Zimerman, B, Williams, M, Bolhofner, K, Craney, JL, DelBello, MP, Soutullo, C (2001). Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. Journal of the American Academy of Child and Adolescent Psychiatry 40, 450455.
Glahn, DC, Bearden, CE, Barguil, M, Barrett, J, Reichenberg, A, Bowden, CL, Soares, JC, Velligan, DI (2007). The neurocognitive signature of psychotic bipolar disorder. Biological Psychiatry 62, 910916.
Glahn, DC, Bearden, CE, Niendam, TA, Escamilla, MA (2004). The feasibility of neuropsychological endophenotypes in the search for genes associated with bipolar affective disorder. Bipolar Disorders 6, 171182.
Gopin, CB, Burdick, KE, DeRosse, P, Goldberg, TE, Malhotra, AK (2011). Emotional modulation of response inhibition in stable patients with bipolar I disorder: a comparison with healthy and schizophrenia subjects. Bipolar Disorders 13, 164172.
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
Gourovitch, ML, Torrey, EF, Gold, JM, Randolph, C, Weinberger, DR, Goldberg, TE (1999). Neuropsychological performance of monozygotic twins discordant for bipolar disorder. Biological Psychiatry 45, 639646.
Hall, M-H, Smoller, JW, Cook, NR, Shulze, K, Hyon Lee, P, Taylor, G, Bramon, E, Coleman, MJ, Murray, RM, Salisbury, DF, Levy, DL (2012). Patterns of deficits in brain function in bipolar disorder and schizophrenia: a cluster analytic study. Psychiatry Research 200, 272280.
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980988.
Keri, S, Kelemen, O, Benedek, G, Janka, Z (2001). Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach. Psychological Medicine 31, 915922.
Kovacs, M (1992). Children's Depression Inventory: Manual. Multi-Health Systems: North Tonawanda, NY.
Kremen, WS, Faraone, SV, Seidman, LJ, Pepple, JR, Tsuang, MT (1998). Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands. Psychiatry Research 79, 227240.
Langenecker, SA, Saunders, EF, Kade, AM, Ransom, MT, McInnis, MG (2010). Intermediate: cognitive phenotypes in bipolar disorder. Journal of Affective Disorders 122, 285293.
Larson, ER, Shear, PK, Krikorian, R, Welge, J, Strakowski, SM (2005). Working memory and inhibitory control among manic and euthymic patients with bipolar disorder. Journal of the International Neuropsychological Society 11, 163172.
Leckman, JF, Sholomskas, D, Thompson, WD, Belanger, A, Weissman, MM (1982). Best estimate of lifetime psychiatric diagnosis: a methodological study. Archives of General Psychiatry 39, 879883.
Levy, B, Weiss, RD (2010). Neurocognitive impairment and psychosis in bipolar I disorder during early remission from an acute episode of mood disturbance. Journal of Clinical Psychiatry 71, 201206.
Lewandowski, K, Sperry, S, Cohen, B, Öngür, D (2014). Cognitive variability in psychotic disorders: a cross-diagnostic cluster analysis. Psychological Medicine 44, 32393248.
Martinez-Aran, A, Vieta, E, Reinares, M, Colom, F, Torrent, C, Sanchez-Moreno, J, Benabarre, A, Goikolea, JM, Comes, M, Salamero, M (2004). Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. American Journal of Psychiatry 161, 262270.
Maxwell, ME (1992). Family Interview for Genetic Studies. Clinical Neurogenetics Branch, Intramural Research Program, NIMH: Bethesda, MD.
McClure, EB, Treland, JE, Snow, J, Schmajuk, M, Dickstein, DP, Towbin, KE, Charney, DS, Pine, DS, Leibenluft, E (2005). Deficits in social cognition and response flexibility in pediatric bipolar disorder. American Journal of Psychiatry 162, 16441651.
McDonald, S, Flanagan, S, Martin, I, Saunders, C (2004). The ecological validity of TASIT: a test of social perception. Neuropsychological Rehabilitation 14, 285302.
McIntosh, AM, Harrison, LK, Forrester, K, Lawrie, SM, Johnstone, EC (2005). Neuropsychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives. British Journal of Psychiatry 186, 378385.
Mitchell, PB, Frankland, A, Hadzi-Pavlovic, D, Roberts, G, Corry, J, Wright, A, Loo, CK, Breakspear, M (2011). Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees. British Journal of Psychiatry 199, 303309.
Mitchell, PB, Johnston, AK, Corry, J, Ball, JR, Malhi, GS (2009). Characteristics of bipolar disorder in an Australian specialist outpatient clinic: comparison across large datasets. Australian and New Zealand Journal of Psychiatry 43, 109117.
Montag, C, Elrich, A, Neuhaus, K, Dziobek, I, Heekeren, HR, Heinz, A, Gallinat, J (2010). Theory of mind impairments in euthymic bipolar patients. Journal of Affective Disorders 123, 264269.
Nehra, R, Chakrabarti, S, Pradhan, BK, Khehra, N (2006). Comparison of cognitive functions between first-and multi-episode bipolar affective disorders. Journal of Affective Disorders 93, 185192.
Nurnberger, JI, Blehar, MC, Kaufmann, CA, York-Cooler, C, Simpson, SG, Harkavy-Friedman, J, Severe, JB, Malaspina, D, Reich, T (1994). Diagnostic Interview for Genetic Studies: rationale, unique features, and training. Archives of General Psychiatry 51, 849859.
Nurnberger, JI, McInnis, M, Reich, W, Kastelic, E, Wilcox, HC, Glowinski, A, Mitchell, P, Fisher, C, Erpe, M, Gershon, ES, Berrettini, W, Laite, G, Schweitzer, R, Rhoadarmer, K, Coleman, VV, Cai, X, Azzouz, F, Liu, H, Kamali, M, Brucksch, C, Monahan, PO (2011). A high-risk study of bipolar disorder: childhood clinical phenotypes as precursors of major mood disorders. Archives of General Psychiatry 68, 10121020.
Olley, AL, Malhi, GS, Bachelor, J, Cahill, CM, Mitchell, PB, Berk, M (2005). Executive functioning and theory of mind in euthymic bipolar disorder. Bipolar Disorders 7, 4352.
Olvet, DM, Burdick, KE, Cornblatt, BA (2013). Assessing the potential to use neurocognition to predict who is at risk for developing bipolar disorder: a review of the literature. Cognitive Neuropsychiatry 18, 129145.
Perich, T, Lau, P, Hadzi-Pavlovic, D, Roberts, G, Frankland, A, Wright, A, Green, M, Breakspear, M, Corry, J, Radlinska, B, McCormack, C, Joslyn, C, Levy, F, Lenroot, R, Nurnberger, Jr. JI, Mitchell, PB (2015). What clinical features precede the onset of bipolar disorder? Journal of Psychiatric Research 62, 7177.
Post, RM, Fleming, J, Kapczinski, F (2012). Neurobiological correlates of illness progression in the recurrent affective disorders. Journal of Psychiatric Research 46, 561573.
Randolph, C, Tierney, MC, Mohr, E, Chase, TN (1998). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. Journal of Clinical and Experimental Neuropsychology 20, 310319.
Roberts, G, Green, MJ, Breakspear, M, McCormack, C, Frankland, A, Wright, A, Levy, F, Lenroot, R, Chan, HN, Mitchell, PB (2013). Reduced inferior frontal gyrus activation during response inhibition to emotional stimuli in youth at high risk of bipolar disorder. Biological Psychiatry 74, 5561.
Schenkel, LS, Chamberlain, TF, Towne, TL (2014). Impaired theory of mind and psychosocial functioning among pediatric patients with type I versus type II bipolar disorder. Psychiatry Research 215, 740746.
Schneider, MR, DelBello, MP, McNamara, RK, Strakowski, SM, Adler, CM (2012). Neuroprogression in bipolar disorder. Bipolar Disorders 14, 356374.
Sitskoorn, MM, Aleman, A, Ebisch, SJ, Appels, MC, Kahn, RS (2004). Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophrenia Research 71, 285295.
Strakowski, SM, Adler, CM, Holland, SK, Mills, N, DelBello, MP (2004). A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology 29, 17341740.
Trotta, A, Murray, RM, MacCabe, JH (2014). Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A systematic review and meta-analysis. Psychological Medicine 45, 381394.
Wechsler, D (1999). Wechsler Abbreviated Scale of Intelligence: WASI. The Psychological Corporation, Harcourt Brace & Company: New York.
Wessa, M, Houenou, J, Paillere-Martinot, ML, Berthoz, S, Artiges, E, Leboyer, M, Martinot, JL (2007). Fronto-striatal overactivation in euthymic bipolar patients during an emotional go/nogo task. American Journal of Psychiatry 164, 638646.
Young, A, Perrett, C, Calder, A, Sprengelmeyer, R, Ekman, P (2002). Facial Expressions of Emotion: Stimuli and Tests (FEEST). Thames Valley Test Company: Bury St Edmunds.
Zalla, T, Joyce, C, Szoke, A, Schurhoff, F, Pillon, B, Komano, O, Perez-Diaz, F, Bellivier, F, Alter, C, Dubois, B, Rouillon, F, Houde, O, Leboyer, M (2004). Executive dysfunctions as potential markers of familial vulnerability to bipolar disorder and schizophrenia. Psychiatry Research 121, 207217.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed