Skip to main content

Cognitive remediation: potential novel brain-based treatment for bipolar disorder in children and adolescents

  • Daniel P. Dickstein (a1), Grace K. Cushman (a1), Kerri L. Kim (a1), Alexandra B. Weissman (a1) and Ezra Wegbreit (a1)...

Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data show that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD.

Corresponding author
*Address for correspondence: Daniel P. Dickstein, MD, Pediatric Mood, Imaging, & NeuroDevelopment (PediMIND) Program, Bradley Hospital, 1011 Veterans Memorial Parkway, East Providence, RI 02915, USA.(Email:
Hide All
1. Blader, JC, Carlson, GA. Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996–2004. Biol Psychiatry. 2007; 62(2): 107114.
2. Moreno, C, Laje, G, Blanco, C, Jiang, H, Schmidt, AB, Olfson, M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007; 64(9): 10321039.
3. Van Meter, AR, Moreira, AL, Youngstrom, EA. Meta-analysis of epidemiologic studies of pediatric bipolar disorder. J Clin Psychiatry. 2011; 72(9): 12501256.
4. Grant, BF, Stinson, FS, Hasin, DS, et al. Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2005; 66(10): 12051215.
5. Dickstein, DP, Rich, BA, Binstock, AB, et al. Comorbid anxiety in phenotypes of pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2005; 15(4): 534548.
6. Birmaher, B, Axelson, D, Goldstein, B, et al. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009; 166(7): 795804.
7. Goldstein, TR, Ha, W, Axelson, DA, et al. Predictors of prospectively examined suicide attempts among youth with bipolar disorder. Arch Gen Psychiatry. 2012; 69(11): 11131122.
8. Haas, M, DelBello, MP, Pandina, G, et al. Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2009; 11(7): 687700.
9. Wagner, KD, Redden, L, Kowatch, RA, et al. A double-blind, randomized, placebo-controlled trial of divalproex extended-release in the treatment of bipolar disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2009; 48(5): 519532.
10. Geller, B, Luby, JL, Joshi, P, et al. A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Arch Gen Psychiatry. 2012; 69(5): 515528.
11. Miklowitz, DJ, George, EL, Axelson, DA, et al. Family-focused treatment for adolescents with bipolar disorder. J Affect Disord. 2004; 82(Suppl 1): S113S128.
12. Pavuluri, MN, Graczyk, PA, Henry, DB, Carbray, JA, Heidenreich, J, Miklowitz, DJ. Child- and family-focused cognitive-behavioral therapy for pediatric bipolar disorder: development and preliminary results. J Am Acad Child Adolesc Psychiatry. 2004; 43(5): 528537.
13. Fristad, MA. Psychoeducational treatment for school-aged children with bipolar disorder. Dev Psychopathol. 2006; 18(4): 12891306.
14. Fristad, MA, Verducci, JS, Walters, K, Young, ME. Impact of multifamily psychoeducational psychotherapy in treating children aged 8 to 12 years with mood disorders. Arch Gen Psychiatry. 2009; 66(9): 10131021.
15. Axelson, D, Birmaher, B, Strober, M, et al. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006; 63(10): 11391148.
16. Berry, EA, Heaton, PT, Kelton, CM. National estimates of the inpatient burden of pediatric bipolar disorder in the United States. J Ment Health Policy Econ. 2011; 14(3): 115123.
17. Correll, CU, Manu, P, Olshanskiy, V, Napolitano, B, Kane, JM, Malhotra, AK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009; 302(16): 17651773.
18. Vinogradov, S, Fisher, M, Villers-Sidani, E. Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology. 2012; 37(1): 4376.
19. Stern, Y, Zarahn, E, Hilton, HJ, Flynn, J, DeLaPaz, R, Rakitin, B. Exploring the neural basis of cognitive reserve. J Clin Exp Neuropsychol. 2003; 25(5): 691701.
20. Kontis, D, Huddy, V, Reeder, C, Landau, S, Wykes, T. Effects of age and cognitive reserve on cognitive remediation therapy outcome in patients with schizophrenia. Am J Geriatr Psychiatry. 2013; 21(3): 218230.
21. White, HA, Shah, P. Training attention-switching ability in adults with ADHD. J Atten Disord. 2006; 10(1): 4453.
22. McGurk, SR, Twamley, EW, Sitzer, DI, McHugo, GJ, Mueser, KT. A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry. 2007; 164(12): 17911802.
23. Wykes, T, Huddy, V, Cellard, C, McGurk, SR, Czobor, P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. 2011; 168(5): 472485.
24. Elgamal, S, McKinnon, MC, Ramakrishnan, K, Joffe, RT, MacQueen, G. Successful computer-assisted cognitive remediation therapy in patients with unipolar depression: a proof of principle study. Psychol Med. 2007; 37(9): 12291238.
25. Tchanturia, K, Davies, H, Campbell, IC. Cognitive remediation therapy for patients with anorexia nervosa: preliminary findings. Ann Gen Psychiatry. 2007; 6: 14.
26. Deckersbach, T, Nierenberg, AA, Kessler, R, et al. Cognitive rehabilitation for bipolar disorder: An open trial for employed patients with residual depressive symptoms. CNS Neurosci Ther. 2010; 16(5): 298307.
27. Bowie, CR, Gupta, M, Holshausen, K. Cognitive remediation therapy for mood disorders: rationale, early evidence, and future directions. Can J Psychiatry. 2013; 58(6): 319325.
28. Demant, KM, Almer, GM, Vinberg, M, Kessing, LV, Miskowiak, KW. Effects of cognitive remediation on cognitive dysfunction in partially or fully remitted patients with bipolar disorder: study protocol for a randomized controlled trial. Trials. 2013; 14: 378.
29. Solé, B, Bonnin, CM, Mayoral, M, et al. Functional remediation for patients with bipolar II disorder: improvement of functioning and subsyndromal symptoms. Eur Neuropsychopharmacol. 2015; 25(2): 257264.
30. Correa, MS, da Silveira, EM, de Lima, DB, et al. The role of encoding strategies in contextual memory deficits in patients with bipolar disorder. Neuropsychol Rehabil. 2015; 25(1): 122136.
31. Martínez-Arán, A, Vieta, E, Colom, F, et al. Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome. Bipolar Disord. 2004; 6(3): 224232.
32. Cavedini, P, Zorzi, C, Bassi, T, et al. Decision-making functioning as a predictor of treatment outcome in anorexia nervosa. Psychiatry Res. 2006; 145(2–3): 179187.
33. Garrido, G, Barrios, M, Penadés, R, et al. Computer-assisted cognitive remediation therapy: cognition, self-esteem and quality of life in schizophrenia. Schizophr Res. 2013; 150(2–3): 563569.
34. McGurk, SR, Mueser, KT, DeRosa, TJ, Wolfe, R. Work recovery, and comorbidity in schizophrenia: a randomized controlled trial of cognitive remediation. Schizophr Bull. 2009; 35(2): 319335.
35. Patel, A, Knapp, M, Romeo, R, et al. Cognitive remediation therapy in schizophrenia: cost-effectiveness analysis. Schizophr Res. 2010; 120(1–3): 217224.
36. Puig, O, Penades, R, Baeza, I, et al. Cognitive remediation therapy in adolescents with early-onset schizophrenia: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2014; 53(8): 859868.
37. van der Oord, S, Ponsioen, AJ, Geurts, HM, Brink, EL, Prins, PJ. A pilot study of the efficacy of a computerized executive functioning remediation training with game elements for children with ADHD in an outpatient setting: outcome on parent- and teacher-rated executive functioning and ADHD behavior. J Atten Disord. 2014; 18(8): 699712.
38. Green, CT, Long, DL, Green, D, et al. Will working memory training generalize to improve off-task behavior in children with attention-deficit/hyperactivity disorder? Neurotherapeutics. 2012; 9(3): 639648.
39. Gray, SA, Chaban, P, Martinussen, R, et al. Effects of a computerized working memory training program on working memory, attention, and academics in adolescents with severe LD and comorbid ADHD: a randomized controlled trial. J Child Psychol Psychiatry. 2012; 53(12): 12771284.
40. Chacko, A, Bedard, AC, Marks, DJ, et al. A randomized clinical trial of Cogmed Working Memory Training in school-age children with ADHD: a replication in a diverse sample using a control condition. J Child Psychol Psychiatry. 2014; 55(3): 247255.
41. Pelham, WE Jr, Gnagy, EM, Greenslade, KE, Milich, R. Teacher ratings of DSM-III-R symptoms for the disruptive behavior disorders. J Am Acad Child Adolesc Psychiatry. 1992; 31(2): 210218.
42. Klingberg, T, Fernell, E, Olesen, PJ, et al. Computerized training of working memory in children with ADHD—a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2005; 44(2): 177186.
43. Shalev, L, Tsal, Y, Mevorach, C. Computerized progressive attentional training (CPAT) program: effective direct intervention for children with ADHD. Child Neuropsychol. 2007; 13(4): 382388.
44. Rapport, MD, Orban, SA, Kofler, MJ, Friedman, LM. Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes. Clin Psychol Rev. 2013; 33(8): 12371252.
45. Dongen-Boomsma, M, Vollebregt, MA, Buitelaar, JK, Slaats-Willemse, D. Working memory training in young children with ADHD: a randomized placebo-controlled trial. J Child Psychol Psychiatry. 2014; 55(8): 886896.
46. Davidson, RJ. Anxiety and affective style: role of prefrontal cortex and amygdala. Biol Psychiatry. 2002; 51(1): 6880.
47. LeDoux, J. The emotional brain, fear, and the amygdala. Cell Mol Neurobiol. 2003; 23(4–5): 727738.
48. Williams, MA, McGlone, F, Abbott, DF, Mattingley, JB. Differential amygdala responses to happy and fearful facial expressions depend on selective attention. Neuroimage. 2005; 24(2): 417425.
49. McClure, EB, Monk, CS, Nelson, EE, et al. Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Arch Gen Psychiatry. 2007; 64(1): 97106.
50. Lindstrom, KM, Guyer, AE, Mogg, K, et al. Normative data on development of neural and behavioral mechanisms underlying attention orienting toward social-emotional stimuli: an exploratory study. Brain Res. 2009; 1292: 6170.
51. Hardee, JE, Benson, BE, Bar-Haim, Y, et al. Patterns of neural connectivity during an attention bias task moderate associations between early childhood temperament and internalizing symptoms in young adulthood. Biol Psychiatry. 2013; 74(4): 273279.
52. Eldar, S, Apter, A, Lotan, D, et al. Attention bias modification treatment for pediatric anxiety disorders: a randomized controlled trial. Am J Psychiatry. 2012; 169(2): 213220.
53. Shechner, T, Rimon-Chakir, A, Britton, JC, et al. Attention bias modification treatment augmenting effects on cognitive behavioral therapy in children with anxiety: randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2014; 53(1): 6171.
54. Yang, W, Ding, Z, Dai, T, Peng, F, Zhang, JX. Attention bias modification training in individuals with depressive symptoms: a randomized controlled trial. J Behav Ther Exp Psychiatry. In press. DOI: 10.1016/j.jbtep.2014.08.005.
55. Baert, S, De Raedt, R, Schacht, R, Koster, EH. Attentional bias training in depression: therapeutic effects depend on depression severity. J Behav Ther Exp Psychiatry. 2010; 41(3): 265274.
56. Johnson, MH, Dziurawiec, S, Ellis, H, Morton, J. Newborns' preferential tracking of face-like stimuli and its subsequent decline. Cognition. 1991; 40(1–2): 119.
57. Farroni, T, Csibra, G, Simion, F, Johnson, MH. Eye contact detection in humans from birth. Proc Natl Acad Sci U S A. 2002; 99(14): 96029605.
58. Guyer, AE, McClure, EB, Adler, AD, et al. Specificity of facial expression labeling deficits in childhood psychopathology. J Child Psychol Psychiatry. 2007; 48(9): 863871.
59. Seymour, KE, Pescosolido, MF, Reidy, BL, et al. Emotional face identification in youths with primary bipolar disorder or primary ADHD. J Am Acad Child Adolesc Psychiatry. 2013; 52(5): 537546.
60. Brotman, MA, Guyer, AE, Lawson, ES, et al. Facial emotion labeling deficits in children and adolescents at risk for bipolar disorder. Am J Psychiatry. 2008; 165(3): 385389.
61. Rich, BA, Vinton, DT, Roberson-Nay, R, et al. Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder. Proc Natl Acad Sci U S A. 2006; 103(23): 89008905.
62. Pavuluri, MN, O'Connor, MM, Harral, E, Sweeney, JA. Affective neural circuitry during facial emotion processing in pediatric bipolar disorder. Biol Psychiatry. 2007; 62(2): 158167.
63. Kalmar, JH, Wang, F, Chepenik, LG, et al. Relation between amygdala structure and function in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2009; 48(6): 636642.
64. Leibenluft, E, Charney, DS, Towbin, KE, Bhangoo, RK, Pine, DS. Defining clinical phenotypes of juvenile mania. Am J Psychiatry. 2003; 160(3): 430437.
65. Rich, BA, Grimley, ME, Schmajuk, M, Blair, KS, Blair, RJ, Leibenluft, E. Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation. Dev Psychopathol. 2008; 20(2): 529546.
66. Brotman, MA, Rich, BA, Guyer, AE, et al. Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. Am J Psychiatry. 2010; 167(1): 6169.
67. Thomas, LA, Kim, P, Bones, BL, Hinton, K, Milch, HS, Reynolds, RC, Adleman, N, Marsh, AA, Blair, RJR, Pine, DS, Leibenluft, E. Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder. Neuroimage: Clinical. 2013; 2: 637645.
68. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
69. Mostofsky, SH, Simmonds, DJ. Response inhibition and response selection: two sides of the same coin. J Cogn Neurosci. 2008; 20(5): 751761.
70. Verbruggen, F, Logan, GD. Automatic and controlled response inhibition: associative learning in the go/no-go and stop-signal paradigms. J Exp Psychol Gen. 2008; 137(4): 649672.
71. Leibenluft, E, Rich, BA, Vinton, DT, et al. Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder. Am J Psychiatry. 2007; 164(1): 5260.
72. Singh, MK, Chang, KD, Mazaika, P, et al. Neural correlates of response inhibition in pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2010; 20(1): 1524.
73. Blair, RJ, Cipolotti, L. Impaired social response reversal. a case of ‘acquired sociopathy’. Brain. 2000; 123(Pt 6): 11221141.
74. Blair, RJ. The roles of orbital frontal cortex in the modulation of antisocial behavior. Brain Cogn. 2004; 55(1): 198208.
75. Blair, RJ. Psychopathy, frustration, and reactive aggression: the role of ventromedial prefrontal cortex. Br J Psychol. 2010; 101(Pt 3): 383399.
76. Rich, BA, Schmajuk, M, Perez-Edgar, KE, Fox, NA, Pine, DS, Leibenluft, E. Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation. Am J Psychiatry. 2007; 164(2): 309317.
77. Rich, BA, Carver, FW, Holroyd, T, et al. Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation. J Psychiatr Res. 2011; 45(10): 12831294.
78. Cools, R, Clark, L, Owen, AM, Robbins, TW. Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. J Neurosci. 2002; 22(11): 45634567.
79. Dickstein, DP, Treland, JE, Snow, J, et al. Neuropsychological performance in pediatric bipolar disorder. Biol Psychiatry. 2004; 55(1): 3239.
80. Gorrindo, T, Blair, RJ, Budhani, S, Dickstein, DP, Pine, DS, Leibenluft, E. Deficits on a probabilistic response-reversal task in patients with pediatric bipolar disorder. Am J Psychiatry. 2005; 162(10): 19751977.
81. Dickstein, DP, Nelson, EE, McClure, EB, et al. Cognitive flexibility in phenotypes of pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2007; 46(3): 341355.
82. Dickstein, DP, Finger, EC, Brotman, MA, et al. Impaired probabilistic reversal learning in youths with mood and anxiety disorders. Psychol Med. 2010; 40(7): 10891100.
83. Dickstein, DP, Finger, EC, Skup, M, Pine, DS, Blair, JR, Leibenluft, E. Altered neural function in pediatric bipolar disorder during reversal learning. Bipolar Disord. 2010; 12(7): 707719.
84. Adleman, NE, Kayser, R, Dickstein, D, Blair, RJ, Pine, D, Leibenluft, E. Neural correlates of reversal learning in severe mood dysregulation and pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2011; 50(11): 11731185.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

CNS Spectrums
  • ISSN: 1092-8529
  • EISSN: 2165-6509
  • URL: /core/journals/cns-spectrums
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 5
Total number of PDF views: 59 *
Loading metrics...

Abstract views

Total abstract views: 364 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 19th March 2018. This data will be updated every 24 hours.