Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-29T11:17:13.490Z Has data issue: false hasContentIssue false
  • English
  • Français

Neurocognitive impairment in unaffected siblings of youth with bipolar disorder

Published online by Cambridge University Press:  11 December 2008

A. E. Doyle ,
J. Wozniak ,
T. E. Wilens ,
A. Henin ,
L. J. Seidman ,
C. Petty ,
R. Fried ,
L. M. Gross ,
S. V. Faraone  and
J. Biederman
A. E. Doyle*
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
J. Wozniak
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
T. E. Wilens
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
A. Henin
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
L. J. Seidman
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
C. Petty
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
R. Fried
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
L. M. Gross
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
S. V. Faraone
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
J. Biederman
Affiliation:
Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
*
*Address for correspondence: A. E. Doyle, Ph.D., Massachusetts General Hospital, Child Psychiatry Service, YAW 6-6A, 55 Fruit Street, Boston, MA02114, USA. (Email: doylea@helix.mgh.harvard.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

There is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and ‘executive’ functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis.

Method

Subjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey–Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test – Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD).

Results

Principal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged ⩾12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor.

Conclusions

Neurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition.

Keywords

Endophenotypeexecutive functionspediatric bipolar disorder
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 8 , August 2009 , pp. 1253 - 1263
Copyright
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Aspects of this work were presented as a poster at the 2005 National Institute of Mental Health (NIMH) Pediatric Bipolar Conference in Chicago, IL, USA.

References

Barkley, RA (1997). Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychological Bulletin 121, 65–94.CrossRefGoogle ScholarPubMed
Barnett, JH, Salmond, CH, Jones, PB, Sahakian, BJ (2006). Cognitive reserve in neuropsychiatry. Psychological Medicine 36, 1053–1064.CrossRefGoogle ScholarPubMed
Bearden, CE, Glahn, DC, Caetano, S, Olvera, RL, Fonseca, M, Najt, P, Hunter, K, Pliszka, SR, Soares, JC (2007). Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder. Bipolar Disorders 9 (Suppl. 1), 145–159.CrossRefGoogle ScholarPubMed
Bernstein, JH, Waber, DP (1996). Developmental Scoring System for the Rey–Osterrieth Complex Figure. Psychological Assessment Resources, Inc.: Odessa, FL.Google Scholar
Biederman, J (2003). Pediatric bipolar disorder coming of age. Biological Psychiatry 53, 931–934.CrossRefGoogle ScholarPubMed
Biederman, J, James, RS (2004). Furthering the scientific foundation of pediatric bipolar disorder. Journal of Affective Disorders 82 (Suppl. 1), S1–S3.CrossRefGoogle ScholarPubMed
Biederman, J, Petty, CR, Wilens, TE, Spencer, T, Henin, A, Faraone, SV, Mick, E, Monuteaux, M, Kenealey, D, Mirto, T, Wozniak, J (in press). Examination of concordance between maternal and youth reports in the diagnosis of pediatric bipolar disorder. Bipolar Disorders.Google Scholar
Borchardt, CM, Bernstein, GA (1995). Comorbid disorders in hospitalized bipolar adolescents compared with unipolar depressed adolescents. Child Psychiatry and Human Development 26, 11–18.CrossRefGoogle ScholarPubMed
Clark, L, Sarna, A, Goodwin, GM (2005). Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression. American Journal of Psychiatry 162, 1980–1982.CrossRefGoogle Scholar
Delis, D, Kramer, J, Kaplan, E, Ober, B (1994). The California Verbal Learning Test – Children's Version. The Psychological Corporation: San Antonio, TX.Google Scholar
Delis, DC, Kramer, JH, Kaplan, E, Ober, BA (2000). California Verbal Learning Test – Second Edition. The Psychological Corporation: San Antonio, TX.Google Scholar
Dickstein, DP, Nelson, EE, McClure, EB, Grimley, ME, Knopf, L, Brotman, MA, Rich, BA, Pine, DS, Leibenluft, E (2007). Cognitive flexibility in phenotypes of pediatric bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 46, 341–355.CrossRefGoogle ScholarPubMed
Dickstein, DP, Treland, JE, Snow, J, McClure, EB, Mehta, MS, Towbin, KE, Pine, DS, Leibenluft, E (2004). Neuropsychological performance in pediatric bipolar disorder. Biological Psychiatry 55, 32–39.CrossRefGoogle ScholarPubMed
Doyle, AE, Biederman, J, Seidman, LJ, Reske-Nielsen, J, Faraone, SV (2005 a). Neuropsychological functioning in relatives of girls with and without ADHD. Psychological Medicine 35, 1121–1132.CrossRefGoogle ScholarPubMed
Doyle, AE, Faraone, SV, Seidman, LJ, Willcutt, EG, Nigg, JT, Waldman, ID, Pennington, BF, Peart, J, Biederman, J (2005 b). Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD? Journal of Child Psychology and Psychiatry 46, 774–803.CrossRefGoogle ScholarPubMed
Doyle, AE, Ferreira, MA, Sklar, PB, Lasky-Su, J, Petty, C, Fusillo, SJ, Seidman, LJ, Willcutt, EG, Smoller, JW, Purcell, S, Biederman, J, Faraone, SV (2008). Multivariate genomewide linkage scan of neurocognitive traits and ADHD symptoms: suggestive linkage to 3q13. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. Published online: 30 October 2008. PMID: 18973233.CrossRefGoogle ScholarPubMed
Doyle, AE, Wilens, T, Kwon, A, Seidman, LJ, Faraone, SV, Fried, R, Swezey, A, Snyder, L, Biederman, J (2005 c). Neuropsychological functioning in youth with bipolar disorder. Biological Psychiatry 58, 540–548.CrossRefGoogle ScholarPubMed
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, 1163–1170.CrossRefGoogle ScholarPubMed
Faraone, S, Glatt, S, Tsuang, M (2003). The genetics of pediatric onset bipolar disorder. Biological Psychiatry 53, 970–977.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Mennin, D, Russell, RL (1998). Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness. American Journal of Medical Genetics 81, 108–116.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
First, M, Spitzer, R, Gibbon, M, Williams, J (1997). Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Press: Washington, DC.Google Scholar
Flint, J, Munafo, MR (2007). The endophenotype concept in psychiatric genetics. Psychological Medicine 37, 163–180.CrossRefGoogle ScholarPubMed
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, 838–839.CrossRefGoogle Scholar
Geller, B, Tillman, R, Bolhofner, K, Zimerman, B, Strauss, NA, Kaufmann, P (2006). Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity. Archives of General Psychiatry 63, 1130–1138.CrossRefGoogle ScholarPubMed
Glahn, DC, Bearden, CE, Caetano, S, Fonseca, M, Najt, P, Hunter, K, Pliszka, SR, Olvera, RL, Soares, JC (2005). Declarative memory impairment in pediatric bipolar disorder. Bipolar Disorders 7, 546–554.CrossRefGoogle ScholarPubMed
Golden, CJ (1978). Stroop Color and Word Test: A Manual for Clinical and Experimental Use. Stoelting, Co.: Chicago, IL.Google Scholar
Goldstein, TR, Birmaher, B, Axelson, D, Ryan, ND, Strober, MA, Gill, MK, Valeri, S, Chiappetta, L, Leonard, H, Hunt, J, Bridge, JA, Brent, DA, Keller, M (2005). History of suicide attempts in pediatric bipolar disorder: factors associated with increased risk. Bipolar Disorders 7, 525–535.CrossRefGoogle ScholarPubMed
Gottesman, II, Gould, TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
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, 639–646.CrossRefGoogle ScholarPubMed
Heaton, RK, Chelune, GJ, Talley, JL, Kay, GG, Curtiss, G (1993). Wisconsin Card Sort Test Manual: Revised and Expanded. Psychological Assessment Resources, Inc.: Odessa, FL.Google Scholar
Henin, A, Mick, E, Biederman, J, Fried, R, Wozniak, J, Faraone, SV, Harrington, K, Davis, S, Doyle, AE (2007). Can bipolar disorder-specific neuropsychological impairments in children be identified? Journal of Consulting and Clinical Psychology 75, 210–220.CrossRefGoogle ScholarPubMed
Jaeger, J, Tatsuoka, C, Berns, S, Varadi, F, Czobor, P, Uzelac, S (2006). Associating functional recovery with neurocognitive profiles identified using partially ordered classification models. Schizophrenia Research 85, 40–48.CrossRefGoogle ScholarPubMed
Keri, S, Kelemen, O, Benedek, G, Janka, Z (2001). Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach. Psychological Medicine 31, 915–922.CrossRefGoogle ScholarPubMed
Kuntsi, J, Rijsdijk, F, Ronald, A, Asherson, P, Plomin, R (2005). Genetic influences on the stability of attention-deficit/hyperactivity disorder symptoms from early to middle childhood. Biological Psychiatry 57, 647–654.CrossRefGoogle ScholarPubMed
Lahey, B, Pelham, W, Stein, M, Loney, J, Trapini, C, Nugent, K, Kipp, H, Schmidt, E, Lee, S, Cale, M, Gold, E, Hartung, CM, Willcutt, E, Baumann, B (1998). Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children. Journal of the American Academy of Child and Adolescent Psychiatry 37, 695–702.CrossRefGoogle ScholarPubMed
Leibenluft, E, Rich, BA, Vinton, DT, Nelson, EE, Fromm, SJ, Berghorst, LH, Joshi, P, Robb, A, Schachar, RJ, Dickstein, DP, McClure, EB, Pine, DS (2007). Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder. American Journal of Psychiatry 164, 52–60.CrossRefGoogle ScholarPubMed
McClure, EB, Treland, JE, Snow, J, Dickstein, DP, Towbin, KE, Charney, DS, Pine, DS, Leibenluft, E (2005 a). Memory and learning in pediatric bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 44, 461–469.CrossRefGoogle ScholarPubMed
McClure, EB, Treland, JE, Snow, J, Schmajuk, M, Dickstein, DP, Towbin, KE, Charney, DS, Pine, DS, Leibenluft, E (2005 b). Deficits in social cognition and response flexibility in pediatric bipolar disorder. American Journal of Psychiatry 162, 1644–1651.CrossRefGoogle ScholarPubMed
Meyer, SE, Carlson, GA, Wiggs, EA, Martinez, PE, Ronsaville, DS, Klimes-Dougan, B, Gold, PW, Radke-Yarrow, M (2004). A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder. Development and Psychopathology 16, 461–476.CrossRefGoogle ScholarPubMed
Monchi, O, Petrides, M, Petre, V, Worsley, K, Dagher, A (2001). Wisconsin Card Sorting revisited: distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging. Journal of Neuroscience 21, 7733–7741.CrossRefGoogle ScholarPubMed
Murphy, FC, Sahakian, BJ (2001). Neuropsychology of bipolar disorder. British Journal of Psychiatry 178 (Suppl. 41), S120–S127.CrossRefGoogle ScholarPubMed
Neuman, R, Geller, B, Rice, J, Todd, R (1997). Increased prevalence and earlier onset of mood disorders among relatives of prepubertal versus adult probands. Journal of the American Academy of Child and Adolescent Psychiatry 36, 466–473.CrossRefGoogle ScholarPubMed
Orvaschel, H (1994). Schedule for Affective Disorder and Schizophrenia for School-Age Children Epidemiologic Version. Nova Southeastern University, Center for Psychological Studies: Ft Lauderdale.Google Scholar
Osterrieth, PA (1944). Le test de copie d'une figure complexe. Archives de Psychologie 30, 206–256.Google Scholar
Pavuluri, MN, Schenkel, LS, Aryal, S, Harral, EM, Hill, SK, Herbener, ES, Sweeney, JA (2006). Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients. American Journal of Psychiatry 163, 286–293.CrossRefGoogle ScholarPubMed
Pennington, BF, Ozonoff, S (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry 37, 51–87.CrossRefGoogle ScholarPubMed
Polderman, TJ, Gosso, MF, Posthuma, D, Van Beijsterveldt, TC, Heutink, P, Verhulst, FC, Boomsma, DI (2006). A longitudinal twin study on IQ, executive functioning, and attention problems during childhood and early adolescence. Acta Neurologica Belgica 106, 191–207.Google ScholarPubMed
Quraishi, S, Frangou, S (2002). Neuropsychology of bipolar disorder: a review. Journal of Affective Disorders 72, 209–226.CrossRefGoogle ScholarPubMed
Rucklidge, JJ (2006). Impact of ADHD on the neurocognitive functioning of adolescents with bipolar disorder. Biological Psychiatry 60, 921–928.CrossRefGoogle ScholarPubMed
Sattler, JM (1988). Assessment of Children. Jerome M. Sattler: San Diego, CA.Google Scholar
Savitz, JB, Solms, M, Ramesar, RS (2005). Neurocognitive function as an endophenotype for genetic studies of bipolar affective disorder. Neuromolecular Medicine 7, 275–286.CrossRefGoogle ScholarPubMed
Seidman, LJ, Breiter, HC, Goodman, JM, Goldstein, JM, Woodruff, PW, O'Craven, K, Savoy, R, Tsuang, MT, Rosen, BR (1998). A functional magnetic resonance imaging study of auditory vigilance with low and high information processing demands. Neuropsychology 12, 505–518.CrossRefGoogle ScholarPubMed
Sheese, BE, Rothbart, MK, Posner, MI, White, LK, Fraundorf, SH (2008). Executive attention and self-regulation in infancy Infant Behavior and Development 31, 501–510.CrossRefGoogle Scholar
Sobczak, S, Honig, A, Schmitt, JA, Riedel, WJ (2003). Pronounced cognitive deficits following an intravenous L-tryptophan challenge in first-degree relatives of bipolar patients compared to healthy controls. Neuropsychopharmacology 28, 711–719.CrossRefGoogle ScholarPubMed
Sobczak, S, Riedel, WJ, Booij, I, Aan Het Rot, M, Deutz, NE, Honig, A (2002). Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers. Psychological Medicine 32, 503–515.CrossRefGoogle ScholarPubMed
Strober, M, Morrell, W, Burroughs, J, Lampert, C, Danforth, H, Freeman, R (1988). A family study of bipolar I disorder in adolescence: early onset of symptoms linked to increased familial loading and lithium resistance. Journal of Affective Disorders 15, 255–268.CrossRefGoogle ScholarPubMed
Torres, IJ, Boudreau, VG, Yatham, LN (2007). Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis. Acta Psychiatrica Scandinavica Supplementum 434, 17–26.CrossRefGoogle Scholar
Wechsler, D (1991). Manual for the Wechsler Intelligence Scale for Children – Third Edition. The Psychological Corporation, Harcourt Brace Jovanovich, Inc.: San Antonio, TX.Google Scholar
Wechsler, D (1997). Wechsler Adult Intelligence Scale III. The Psychological Corporation: San Antonio, TX.Google Scholar
Werry, JS, Reeves, JC, Elkind, GS (1987). Attention deficit, conduct, oppositional, and anxiety disorders in children: I. A review of research on differentiating characteristics. Journal of the American Academy of Child and Adolescent Psychiatry 26, 133–143.CrossRefGoogle Scholar
Wilens, T, Biederman, J, Kwon, A, Ditterline, J, Forkner, P, Chase, R, Moore, H, Swezey, A, Snyder, L, Morris, M, Henin, A, Wozniak, J, Faraone, SV (2004). Risk for substance use disorders in adolescents with bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 43, 1380–1386.CrossRefGoogle ScholarPubMed
Wozniak, J, Biederman, J, Kwon, A, Mick, E, Faraone, SV, Orlovsky, K, Schnare, L, Cargol, C, Van Grondelle, A (2005). How cardinal are cardinal symptoms in pediatric bipolar disorder? An examination of clinical correlates. Biological Psychiatry 58, 583–588.CrossRefGoogle ScholarPubMed
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, 207–217.CrossRefGoogle Scholar
Zeger, SL, Liang, KY (1986). Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42, 121–130.CrossRefGoogle ScholarPubMed