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Cross-Disorder Cognitive Impairments in Youth Referred for Neuropsychiatric Evaluation

Published online by Cambridge University Press:  04 August 2017

Alysa E. Doyle ,
Pieter J. Vuijk ,
Nathan D. Doty ,
Lauren M. McGrath ,
Brian L. Willoughby ,
Ellen H. O’Donnell ,
H. Kent Wilson ,
Mary K. Colvin ,
Deanna C. Toner  and
Kelsey E. Hudson
...Show all authors
Alysa E. Doyle*
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts
Pieter J. Vuijk
Affiliation:
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
Nathan D. Doty
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts
Lauren M. McGrath
Affiliation:
Department of Psychology, University of Denver, Denver, Colorado
Brian L. Willoughby
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts
Ellen H. O’Donnell
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts
H. Kent Wilson
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts
Mary K. Colvin
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts
Deanna C. Toner
Affiliation:
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
Kelsey E. Hudson
Affiliation:
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
Jessica E. Blais
Affiliation:
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
Hillary L. Ditmars
Affiliation:
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts
Stephen V. Faraone
Affiliation:
Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York
Larry J. Seidman
Affiliation:
Harvard Medical School, Boston, Massachusetts Commonwealth Research Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Ellen B. Braaten
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts Harvard Medical School, Boston, Massachusetts
*
Correspondence and reprint requests to: Alysa E. Doyle, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN 6240, Boston, MA 02114. E-mail: [email protected]
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Abstract

Objectives: Studies suggest that impairments in some of the same domains of cognition occur in different neuropsychiatric conditions, including those known to share genetic liability. Yet, direct, multi-disorder cognitive comparisons are limited, and it remains unclear whether overlapping deficits are due to comorbidity. We aimed to extend the literature by examining cognition across different neuropsychiatric conditions and addressing comorbidity. Methods: Subjects were 486 youth consecutively referred for neuropsychiatric evaluation and enrolled in the Longitudinal Study of Genetic Influences on Cognition. First, we assessed general ability, reaction time variability (RTV), and aspects of executive functions (EFs) in youth with non-comorbid forms of attention-deficit/hyperactivity disorder (ADHD), mood disorders and autism spectrum disorder (ASD), as well as in youth with psychosis. Second, we determined the impact of comorbid ADHD on cognition in youth with ASD and mood disorders. Results: For EFs (working memory, inhibition, and shifting/ flexibility), we observed weaknesses in all diagnostic groups when participants’ own ability was the referent. Decrements were subtle in relation to published normative data. For RTV, weaknesses emerged in youth with ADHD and mood disorders, but trend-level results could not rule out decrements in other conditions. Comorbidity with ADHD did not impact the pattern of weaknesses for youth with ASD or mood disorders but increased the magnitude of the decrement in those with mood disorders. Conclusions: Youth with ADHD, mood disorders, ASD, and psychosis show EF weaknesses that are not due to comorbidity. Whether such cognitive difficulties reflect genetic liability shared among these conditions requires further study. (JINS, 2018, 24, 91–103)

Keywords

Executive functionsReaction time variability (RTV)ADHDAutism spectrum disorderMood disordersPsychosis
Type
Special Section: Lifespan Neuropsychology
Information
Journal of the International Neuropsychological Society , Volume 24 , Issue 1 , January 2018 , pp. 91 - 103
Copyright
Copyright © The International Neuropsychological Society 2017 

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References

REFERENCES

Agnew-Blais, J., & Seidman, L.J. (2013). Neurocognition in youth and young adults under age 30 at familial risk for schizophrenia: A quantitative and qualitative review. Cognitive Neuropsychiatry, 18(1-2), 44–82.Google Scholar
Alderson, R.M., Kasper, L.J., Hudec, K.L., & Patros, C.H. (2013). Attention-deficit/hyperactivity disorder (ADHD) and working memory in adults: A meta-analytic review. Neuropsychology, 27(3), 287–302.Google Scholar
Barkley, R.A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121(1), 65–94.Google Scholar
Bidwell, L.C., Willcutt, E.G., Defries, J.C., & Pennington, B.F. (2007). Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder. Biological Psychiatry, 62(9), 991–998.Google Scholar
Biederman, J., Petty, C., Fried, R., Fontanella, J., Doyle, A.E., Seidman, L.J., && Faraone, S.V. (2006). Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder. American Journal of Psychiatry, 163(10), 1730–1738.CrossRefGoogle ScholarPubMed
Bora, E., Vahip, S., & Akdeniz, F. (2006). Sustained attention deficits in manic and euthymic patients with bipolar disorder. Progress in Neuro-psychopharmacologogy & Biological Psychiatry, 30(6), 1097–1102.Google Scholar
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(1-2), 1–20.Google Scholar
Bourne, C., Aydemir, O., Balanza-Martinez, V., Bora, E., Brissos, S., Cavanagh, J.T., & Goodwin, G.M. (2013). Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: An individual patient data meta-analysis. Acta Psychiatrica Scandinavica, 128(3), 149–162.Google Scholar
Brotman, M.A., Rooney, M.H., Skup, M., Pine, D.S., & Leibenluft, E. (2009). Increased intrasubject variability in response time in youths with bipolar disorder and at-risk family members. Journal of the American Academy of Child and Adolescent Psychiatry, 48(6), 628–635.Google Scholar
Buckley, P.F., Miller, B.J., Lehrer, D.S., & Castle, D.J. (2009). Psychiatric comorbidities and schizophrenia. Schizophrenia Bulletin, 35(2), 383–402.CrossRefGoogle ScholarPubMed
Conners, C. (2000). Conners Continuous Performance Test II (CPT-II): Technical Guide and Software Manual. North Tonwanda, NY: Multi-Health Systems.Google Scholar
Craddock, N., Kendler, K., Neale, M., Nurnberger, J., Purcell, S., Rietschel, M., & Thapar, A. (2009). Dissecting the phenotype in genome-wide association studies of psychiatric illness. British Journal of Psychiatry, 195(2), 97–99.Google Scholar
Craig, F., Margari, F., Legrottaglie, A.R., Palumbi, R., de Giambattista, C., & Margari, L. (2016). A review of executive function deficits in autism spectrum disorder and attention-deficit/hyperactivity disorder. Neuropsychiatric Disease and Treatment, 12, 1191–1202.Google Scholar
Cuthbert, B.N. (2015). Research domain criteria: Toward future psychiatric nosologies. Dialogues in Clinical Neuroscience, 17(1), 89–97.Google Scholar
Dajani, D.R., Llabre, M.M., Nebel, M.B., Mostofsky, S.H., & Uddin, L.Q. (2016). Heterogeneity of executive functions among comorbid neurodevelopmental disorders. Scientific Reports, 6, 36566.Google Scholar
Delis, D.C., Kramer, J.H., Kaplan, E., & Holdnack, J. (2004). Reliability and validity of the Delis-Kaplan Executive Function System: An update. Journal of the International Neuropsychological Society, 10(2), 301–303.Google Scholar
Denckla, M.B. (1994). Measurement of excutive function. In G.J. Lyon (Ed.), Frames of reference for the assessment of learning disabilities: New views on measurement issues (pp. 117–142). Baltimore: Brooks.Google Scholar
Doyle, A.E., Wozniak, J., Wilens, T.E., Henin, A., Seidman, L.J., Petty, C., & Biederman, J. (2009). Neurocognitive impairment in unaffected siblings of youth with bipolar disorder. Psychological Medicine, 39(8), 1253–1263.CrossRefGoogle ScholarPubMed
Fioravanti, M., Bianchi, V., & Cinti, M.E. (2012). Cognitive deficits in schizophrenia: An updated metanalysis of the scientific evidence. BMC Psychiatry, 12, 64.Google Scholar
Fombonne, E., Bolton, P., Prior, J., Jordan, H., & Rutter, M. (1997). A family study of autism: Cognitive patterns and levels in parents and siblings. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 38(6), 667–683.Google Scholar
Forbes, N.F., Carrick, L.A., McIntosh, A.M., & Lawrie, S.M. (2009). Working memory in schizophrenia: A meta-analysis. Psychological Medicine, 39(6), 889–905.Google Scholar
Frazier, J.A., Giuliano, A.J., Johnson, J.L., Yakutis, L., Youngstrom, E.A., Breiger, D., & Hooper, S.R. (2012). Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study. Journal of the American Academy of Child and Adolescent Psychiatry, 51(5), 496–505.Google Scholar
Geurts, H.M., van den Bergh, S.F., & Ruzzano, L. (2014). Prepotent response inhibition and interference control in autism spectrum disorders: Two meta-analyses. Autism Research, 7, 407–420.Google Scholar
Goldberg, M.C., Mostofsky, S.H., Cutting, L.E., Mahone, E.M., Astor, B.C., Denckla, M.B., &&Landa, R.J. (2005). Subtle executive impairment in children with autism and children with ADHD. Journal of Autism and Developmental Disorders, 35(3), 279–293.CrossRefGoogle ScholarPubMed
Green, M.F. (2006). Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. The Journal of Clinical Psychiatry, 67(10), e12.Google Scholar
Iverson, G.L., Lange, R.T., Viljoen, H., & Brink, J. (2006). WAIS-III General Ability Index in neuropsychiatry and forensic psychiatry inpatient samples. Archives of Clinical Neuropsychology, 21(1), 77–82.Google Scholar
Jacobson, M.W., Delis, D.C., Bondi, M.W., & Salmon, D.P. (2002). Do neuropsychological tests detect preclinical Alzheimer’s disease: Individual-test versus cognitive-discrepancy score analyses. Neuropsychology, 16(2), 132–139.Google Scholar
Joseph, M.F., Frazier, T.W., Youngstrom, E.A., & Soares, J.C. (2008). A quantitative and qualitative review of neurocognitive performance in pediatric bipolar disorder. Journal of Child and Adolescent Psychopharmacology, 18(6), 595–605.CrossRefGoogle ScholarPubMed
Kaiser, S., Roth, A., Rentrop, M., Friederich, H.C., Bender, S., & Weisbrod, M. (2008). Intra-individual reaction time variability in schizophrenia, depression and borderline personality disorder. Brain and Cognition, 66(1), 73–82.Google Scholar
Karalunas, S.L., Geurts, H.M., Konrad, K., Bender, S., & Nigg, J.T. (2014). Annual research review: Reaction time variability in ADHD and autism spectrum disorders: Measurement and mechanisms of a proposed trans-diagnostic phenotype. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 55(6), 685–710.Google Scholar
Kasper, L.J., Alderson, R.M., & Hudec, K.L. (2012). Moderators of working memory deficits in children with attention-deficit/hyperactivity disorder (ADHD): A meta-analytic review. Clinical Psychology Review, 32(7), 605–617.Google Scholar
Kofler, M.J., Rapport, M.D., Sarver, D.E., Raiker, J.S., Orban, S.A., Friedman, L.M., &&Kolomeyer, E.G. (2013). Reaction time variability in ADHD: A meta-analytic review of 319 studies. Clinical Psychology Review, 33(6), 795–811.Google Scholar
Krukow, P., Szaniawska, O., Harciarek, M., Plechawska-Wojcik, M., & Jonak, K. (2017). Cognitive inconsistency in bipolar patients is determined by increased intra-individual variability in initial phase of task performance. Journal of Affective Disorders, 210, 222–225.CrossRefGoogle ScholarPubMed
Kuntsi, J., Eley, T.C., Taylor, A., Hughes, C., Asherson, P., Caspi, A., &&Moffitt, T.E. (2004). Co-occurrence of ADHD and low IQ has genetic origins. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 124B(1), 41–47.Google Scholar
Kuntsi, J., Rogers, H., Swinard, G., Borger, N., van der Meere, J., Rijsdijk, F., &&Asherson, P. (2006). Reaction time, inhibition, working memory and ‘delay aversion’ performance: Genetic influences and their interpretation. Psychological Medicine, 36(11), 1613–1624.Google Scholar
Landis, J.R., & Koch, G.G. (1977). The measurement of observer agreement for categorical variables. Biometrics, 33, 159–174.Google Scholar
Lee, S.H., Ripke, S., Neale, B.M., Faraone, S.V., Purcell, S.M., Perlis, R.H., & Wray, N.R. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45(9), 984–994.Google ScholarPubMed
Lipszyc, J., & Schachar, R. (2010). Inhibitory control and psychopathology: A meta-analysis of studies using the stop signal task. Journal of the International Neuropsychological Society, 16(6), 1064–1076.Google Scholar
Loring, D.W. (1999). INS Dictionary of Neuropsychology. Oxford: Oxford University Press.Google Scholar
Malhotra, D., & Sebat, J. (2012). CNVs: Harbingers of a rare variant revolution in psychiatric genetics. Cell, 148(6), 1223–1241.Google Scholar
McLean, R.L., Johnson Harrison, A., Zimak, E., Joseph, R.M., & Morrow, E.M. (2014). Executive function in probands with autism with average IQ and their unaffected first-degree relatives. Journal of the American Academy of Child and Adolescent Psychiatry, 53(9), 1001–1009.Google Scholar
Miyake, A., & Friedman, N.P. (2012). The nature and organization of individual differences in executive functions: Four general conclusions. Current Directions in Psychological Science, 21(1), 8–14.Google Scholar
Morgan, V.A., Croft, M.L., Valuri, G.M., Zubrick, S.R., Bower, C., McNeil, T.F., && Jablensky, A.V. (2012). Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression. British Journal of Psychiatry, 200(4), 282–289.Google Scholar
Mosconi, M.W., Kay, M., D’Cruz, A.M., Guter, S., Kapur, K., Macmillan, C., & Sweeney, J.A. (2010). Neurobehavioral abnormalities in first-degree relatives of individuals with autism. Archives of General Psychiatry, 67(8), 830–840.Google Scholar
Oerlemans, A.M., Hartman, C.A., de Bruijn, Y.G., Franke, B., Buitelaar, J.K., & Rommelse, N.N. (2015). Cognitive impairments are different in single-incidence and multi-incidence ADHD families. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 56(7), 782–791.Google Scholar
Owens, S.F., Rijsdijk, F., Picchioni, M.M., Stahl, D., Nenadic, I., Murray, R.M., &&Toulopoulou, T. (2011). Genetic overlap between schizophrenia and selective components of executive function. Schizophrenia Research, 127(1-3), 181–187.Google Scholar
Pennington, B.F. (2006). From single to multiple deficit models of developmental disorders. Cognition, 101(2), 385–413.Google Scholar
PGC Cross Disorder Group (2013). Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis. Lancet, 381(9875), 1371–1379.CrossRefGoogle Scholar
Prifitera, A., Weiss, L.G., & Saklofske, D.H. (1998). The WISC-III in context. In A. Prifitera & D.H. Saklofske (Eds.), W1SC-1II clinical use and interpretation: Scientist-practitioner perspective (pp. 1–38). San Diego, CA: Academic Press.Google Scholar
RDoC Cognitive Group. (2011). Cognitive Systems: Workshop Proceedings, Rockville, MD: RDoC Cognitive Group.Google Scholar
Sattler, J.M. (2008). Assessment of children: Cognitive foundations (5th ed.). Mesa, CA: Jerome M. Sattler, Publisher.Google Scholar
Seidman, L.J., Biederman, J., Valera, E.M., Monuteaux, M.C., Doyle, A.E., & Faraone, S.V. (2006). Neuropsychological functioning in girls with attention-deficit/hyperactivity disorder with and without learning disabilities. Neuropsychology, 20(2), 166–177.Google Scholar
Seidman, L.J., Bruder, G., & Giuliano, A.J. (2008). Neuropsychological testing and neurophysiological assessment. In A. Tasman, J. Kay, J.A. Lieberman, M.B. First & M. Maj (Eds.), Psychiatry (3rd ed., pp. 556–569). London: John Wiley and Sons.Google Scholar
Slaats-Willemse, D.I., Swaab-Barneveld, H.J., de Sonneville, L.M., & Buitelaar, J.K. (2007). Family-genetic study of executive functioning in attention-deficit/hyperactivity disorder: Evidence for an endophenotype? Neuropsychology, 21(6), 751–760.Google Scholar
Snijders, T.A.B., & Bosker, R.J. (2012). Multilevel analysis: An introduction to basic and advanced multilevel modeling (2nd ed.). Thousand Oaks, CA: Sage Publishers.Google Scholar
Snitz, B.E., Macdonald, A.W. III, & Carter, C.S. (2006). Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: A meta-analytic review of putative endophenotypes. Schizophrenia Bulletin, 32(1), 179–194.Google Scholar
Snyder, H.R. (2013). Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: A meta-analysis and review. Psychological Bulletin, 139(1), 81–132.Google Scholar
StataCorp. (2015). Stata Statistical Software: Release 14. College Station, TX: StataCorp LP.Google Scholar
Stefanopoulou, E., Manoharan, A., Landau, S., Geddes, J.R., Goodwin, G., & Frangou, S. (2009). Cognitive functioning in patients with affective disorders and schizophrenia: A meta-analysis. International Review of Psychiatry (Abingdon, England), 21(4), 336–356.Google Scholar
Tamm, L., Narad, M.E., Antonini, T.N., O’Brien, K.M., Hawk, L.W. Jr., & Epstein, J.N. (2012). Reaction time variability in ADHD: A review. Neurotherapeutics, 9(3), 500–508.Google Scholar
Thissen, A.J., Luman, M., Hartman, C., Hoekstra, P., van Lieshout, M., Franke, B., & Buitelaar, J.K. (2014). Attention-deficit/hyperactivity disorder (ADHD) and motor timing in adolescents and their parents: Familial characteristics of reaction time variability vary with age. Journal of the American Academy of Child and Adolescent Psychiatry, 53(9), 1010–1019.CrossRefGoogle ScholarPubMed
Toulopoulou, T., Goldberg, T.E., Mesa, I.R., Picchioni, M., Rijsdijk, F., Stahl, D., &&Murray, R.M. (2010). Impaired intellect and memory: A missing link between genetic risk and schizophrenia? Archives of General Psychiatry, 67(9), 905–913.Google Scholar
Toulopoulou, T., Picchioni, M., Rijsdijk, F., Hua-Hall, M., Ettinger, U., Sham, P., …Murray, R. (2007). Substantial genetic overlap between neurocognition and schizophrenia: Genetic modeling in twin samples. Archives of General Psychiatry, 64(12), 1348–1355.Google Scholar
Tulsky, D.S., Saklofske, D.H., Wilkins, C., & Weiss, L.G. (2001). Development of a general ability index for the Wechsler Adult Intelligence Scale--Third Edition. Psychological Assessment, 13(4), 566–571.Google Scholar
Volkert, J., Haubner, J., Kazmaier, J., Glaser, F., Kopf, J., Kittel-Schneider, S., &&Reif, A. (2016). Cognitive deficits in first-degree relatives of bipolar patients: The use of homogeneous subgroups in the search of cognitive endophenotypes. Journal of Neural Transmission (Vienna), 123(8), 1001–1011.Google Scholar
Wagner, S., Muller, C., Helmreich, I., Huss, M., & Tadic, A. (2015). A meta-analysis of cognitive functions in children and adolescents with major depressive disorder. European Child & Adolescent Psychiatry, 24(1), 5–19.Google Scholar
Wechsler, D. (2004). The Wechsler Intelligence Scale for Children—Fourth Edition. New York: Springer.Google Scholar
Wechsler, D. (2008). Wechsler Adult Intelligence Scales -Fourth Edition. New York: Springer.Google Scholar
Westerhausen, R., Kompus, K., & Hugdahl, K. (2011). Impaired cognitive inhibition in schizophrenia: A meta-analysis of the Stroop interference effect. Schizophrenia Research, 133(1-3), 172–181.Google Scholar
Willcutt, E.G., Doyle, A.E., Nigg, J.T., Faraone, S.V., & Pennington, B.F. (2005). Validity of the executive function theory of attention-deficit/hyperactivity disorder: A meta-analytic review. Biological Psychiatry, 57(11), 1336–1346.Google Scholar
Willcutt, E.G., Sonuga-Barke, E., Nigg, J., & Sergeant, J. (2008). Recent developments in neuropsychological models of childhood psychiatric disorders. In T. Banaschewski & L. Rohde (Eds.), Biological Child Psychiatry: Recent Trends and Developments (Vol. 24, pp. 195–226). Basel, Karger.Google Scholar
Wong, D., Maybery, M., Bishop, D.V., Maley, A., & Hallmayer, J. (2006). Profiles of executive function in parents and siblings of individuals with autism spectrum disorders. Genes, Brain, and Behavior, 5(8), 561–576.Google Scholar
Wood, A.C., Rijsdijk, F., Johnson, K.A., Andreou, P., Albrecht, B., Arias-Vasquez, A., & Kuntsi, J. (2011). The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ. Psychological Medicine, 41(4), 861–871.Google Scholar