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Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder

Published online by Cambridge University Press:  16 April 2020

Richard Delorme ,
Véronique Goussé ,
Isabelle Roy ,
Anca Trandafir ,
Flavie Mathieu ,
Marie-Christine Mouren-Siméoni ,
Catalina Betancur  and
Marion Leboyer
Richard Delorme*
Affiliation:
INSERM U513, Neurobiologie et Psychiatrie, Université Paris XII, Créteil, France Service de Psychopathologie de l'Enfant et de l'Adolescent, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France
Véronique Goussé
Affiliation:
INSERM U513, Neurobiologie et Psychiatrie, Université Paris XII, Créteil, France
Isabelle Roy
Affiliation:
INSERM U513, Neurobiologie et Psychiatrie, Université Paris XII, Créteil, France Département de Psychiatrie Adulte, Hôpital Henri Mondor et Albert Chenevier, Assistance Publique- Hôpitaux de Paris, Créteil, France
Anca Trandafir
Affiliation:
Département de Psychiatrie Adulte, Hôpital Henri Mondor et Albert Chenevier, Assistance Publique- Hôpitaux de Paris, Créteil, France
Flavie Mathieu
Affiliation:
INSERM U513, Neurobiologie et Psychiatrie, Université Paris XII, Créteil, France
Marie-Christine Mouren-Siméoni
Affiliation:
Service de Psychopathologie de l'Enfant et de l'Adolescent, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France
Catalina Betancur
Affiliation:
INSERM U513, Neurobiologie et Psychiatrie, Université Paris XII, Créteil, France
Marion Leboyer
Affiliation:
INSERM U513, Neurobiologie et Psychiatrie, Université Paris XII, Créteil, France Département de Psychiatrie Adulte, Hôpital Henri Mondor et Albert Chenevier, Assistance Publique- Hôpitaux de Paris, Créteil, France
*
*Corresponding author. INSERM U513, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil Cedex, France. Tel.: +33 1 49 81 35 14; fax: +33 1 49 81 36 85. E-mail address: richard.delorme@creteil.inserm.fr (R. Delorme).
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Abstract

Background

Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD.

Methods

Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education.

Results

In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency).

Conclusions

Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.

Keywords

EndophenotypeTower of LondonPlanningWorking memory
Type
Genetic Epidemiology and Its Methods
Information
European Psychiatry , Volume 22 , Issue 1 , January 2007 , pp. 32 - 38
Copyright
Copyright © Elsevier Masson SAS 2007

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Footnotes

1

Both authors contributed equally to this work.

References

Ardila, A., Galeano, L.M., Rosselli, M.Toward a model of neuropsychological activity. Neuropsychol Rev 1998;8:171–190.CrossRefGoogle Scholar
Ardila, A., Pineda, D., Rosselli, M.Correlation between intelligence test scores and executive function measures. Arch Clin Neuropsychol 2000;15:31–36.CrossRefGoogle ScholarPubMed
Benton, A.L.Differential behavioral effects in frontal lobe disease. Neuropsychologia 1968;6:53–60.CrossRefGoogle Scholar
Bolton, P., Macdonald, H., Pickles, A., Rios, P., Goode, S., Crowson, M.et al.A case-control family history study of autism. J Child Psychol Psychiatry 1994;35:877–900.CrossRefGoogle ScholarPubMed
Bolton, P.F., Pickles, A., Murphy, M., Rutter, M.Autism, affective and other psychiatric disorders: patterns of familial aggregation. Psychol Med 1998;28:385–395.CrossRefGoogle ScholarPubMed
Buxbaum, J.D., Silverman, J., Keddache, M., Smith, C.J., Hollander, E., Ramoz, N.et al.Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19. Mol Psychiatry 2004;9:144–150.CrossRefGoogle Scholar
Cornblatt, B.A., Malhotra, A.K.Impaired attention as an endophenotype for molecular genetic studies of schizophrenia. Am J Med Genet 2001;105:11–15.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Dawson, G., Munson, J., Estes, A., Osterling, J., McPartland, J., Toth, K.et al.Neurocognitive function and joint attention ability in young children with autism spectrum disorder versus developmental delay. Child Dev 2002;73:345–358.CrossRefGoogle ScholarPubMed
Dawson, G., Webb, S., Schellenberg, G.D., Dager, S., Friedman, S., Aylward, E.et al.Defining the broader phenotype of autism: genetic, brain, and behavioral perspectives. Dev Psychopathol 2002;14:581–611.CrossRefGoogle ScholarPubMed
Demakis, G.J., Harrison, D.W.Relationships between verbal and non-verbal fluency measures: implications for assessment of executive functioning. Psychol Rep 1997;81:43–48.CrossRefGoogle Scholar
Folstein, S.E., Santangelo, S.L., Gilman, S.E., Piven, J., Landa, R., Lainhart, J.et al.Predictors of cognitive test patterns in autism families. J Child Psychol Psychiatry 1999;40:1117–1128.CrossRefGoogle ScholarPubMed
Galderisi, S., Mucci, A., Catapano, F., D'Amato, A.C., Maj, M.Neuropsychological slowness in obsessive-compulsive patients. Is it confined to tests involving the fronto-subcortical systems?. Br J Psychiatry 1995;167:394–398.CrossRefGoogle ScholarPubMed
Goldberg, T.E., Weinberger, D.R.Genes and the parsing of cognitive processes. Trends Cogn Sci 2004;8:325–335.CrossRefGoogle ScholarPubMed
Gottesman, II, Gould, T.D.The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636–645.CrossRefGoogle ScholarPubMed
Goussé, V., Delorme, R., Chabane, N., Perez-Diaz, F., Mathieu, F., Mouren-Siméoni, M.C.et al.Is age at onset associated with executive dysfunction in obsessive-compulsive disorder? Encéphale 2005;31:666–671.CrossRefGoogle ScholarPubMed
Griffith, E.M., Pennington, B.F., Wehner, E.A., Rogers, S.J.Executive functions in young children with autism. Child Dev 1999;70:817–832.CrossRefGoogle ScholarPubMed
Hasler, G., Drevets, W.C., Manji, H.K., Charney, D.S.Discovering endophenotypes for major depression. Neuropsychopharmacology 2004;29:1765–1781.CrossRefGoogle ScholarPubMed
Hill, E.L.Executive dysfunction in autism. Trends Cogn Sci 2004;8:26–32.CrossRefGoogle ScholarPubMed
Hollander, E., Anagnostou, E., Chaplin, W., Esposito, K., Haznedar, M.M., Licalzi, E.et al.Striatal volume on magnetic resonance imaging and repetitive behaviors in autism. Biol Psychiatry 2005;58:226–232.CrossRefGoogle ScholarPubMed
Hollander, E., King, A., Delaney, K., Smith, C.J., Silverman, J.M.Obsessive-compulsive behaviors in parents of multiplex autism families. Psychiatry Res 2003;117:11–16.CrossRefGoogle ScholarPubMed
Hughes, C., Leboyer, M., Bouvard, M.Executive function in parents of children with autism. Psychol Med 1997;27:209–220.CrossRefGoogle ScholarPubMed
Hughes, C., Plumet, M.H., Leboyer, M.Towards a cognitive phenotype for autism: increased prevalence of executive dysfunction and superior spatial span amongst siblings of children with autism. J Child Psychol Psychiatry 1999;40:705–718.CrossRefGoogle ScholarPubMed
Jones-Gotman, M., Milner, B.Design fluency: the invention of nonsense drawings after focal cortical lesions. Neuropsychologia 1977;15:653–674.CrossRefGoogle ScholarPubMed
Kathmann, N., Hochrein, A., Uwer, R., Bondy, B.Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives. Am J Psychiatry 2003;160:696–702.CrossRefGoogle ScholarPubMed
Keith Berg, W., Byrd, D.The Tower of London spatial problem-solving task: enhancing clinical and research implementation. J Clin Exp Neuropsychol 2002;24:586–604.CrossRefGoogle Scholar
Kuelz, A.K., Hohagen, F., Voderholzer, U.Neuropsychological performance in obsessive-compulsive disorder: a critical review. Biol Psychol 2004;65:185–236.CrossRefGoogle ScholarPubMed
Leboyer, M.Searching for alternative phenotypes in psychiatric genetics. Methods Mol Med 2003;77:145–161.Google ScholarPubMed
Lezack, M.D.Lezack, Neuropsychological Assessment. 3rd ed.New York: Oxford University Press; 1995.Google Scholar
Lord, C., Rutter, M., Le Couteur, A.Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994;24:659–685.CrossRefGoogle ScholarPubMed
Maxwell, M.E.Family Interview for Genetic Studies. Clinical Neurogenetic Branch, Intramural Research Program, NIMH 1992.Google Scholar
Micali, N., Chakrabarti, S., Fombonne, E.The broad autism phenotype: findings from an epidemiological survey. Autism 2004;8:21–37.CrossRefGoogle ScholarPubMed
Miguel, E.C., Leckman, J.F., Rauch, S., do Rosario-Campos, M.C., Hounie, A.G., Mercadante, M.T.et al.Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry 2005;10:258–275.CrossRefGoogle ScholarPubMed
Muhle, R., Trentacoste, S.V., Rapin, I.The genetics of autism. Pediatrics 2004;113:472–486.CrossRefGoogle ScholarPubMed
Nestadt, G., Addington, A., Samuels, J., Liang, K.Y., Bienvenu, O.J., Riddle, M.et al.The identification of OCD-related subgroups based on comorbidity. Biol Psychiatry 2003;53:914–920.CrossRefGoogle ScholarPubMed
Nurnberger, J.I. Jr., Blehar, M.C., Kaufmann, C.A., York-Cooler, C., Simpson, S.G., Harkavy-Friedman, J.et al.Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry 1994;51:849–859.CrossRefGoogle ScholarPubMed
Orvaschel, H., Puig-Antich, J., Chambers, W., Tabrizi, M.A., Johnson, R.Retrospective assessment of prepubertal major depression with the Kiddie-SADS-e. J Am Acad Child Psychiatry 1982;21:392–397.CrossRefGoogle ScholarPubMed
Ozonoff, S., Cook, I., Coon, H., Dawson, G., Joseph, R.M., Klin, A.et al.Performance on Cambridge Neuropsychological Test Automated Battery subtests sensitive to frontal lobe function in people with autistic disorder: evidence from the Collaborative Programs of Excellence in Autism network. J Autism Dev Disord 2004;34:139–150.CrossRefGoogle ScholarPubMed
Ozonoff, S., Jensen, J.Brief report: specific executive function profiles in three neurodevelopmental disorders. J Autism Dev Disord 1999;29:171–177.CrossRefGoogle ScholarPubMed
Ozonoff, S., Rogers, S.J., Farnham, J.M., Pennington, B.F.Can standard measures identify subclinical markers of autism? J Autism Dev Disord 1993;23:429–441.CrossRefGoogle ScholarPubMed
Penades, R., Catalan, R., Andres, S., Salamero, M., Gasto, C.Executive function and non-verbal memory in obsessive-compulsive disorder. Psychiatry Res 2005;133:81–90.CrossRefGoogle Scholar
Pennington, B.F., Ozonoff, S.Executive functions and developmental psychopathology. J Child Psychol Psychiatry 1996;37:51–87.CrossRefGoogle ScholarPubMed
Purcell, R., Maruff, P., Kyrios, M., Pantelis, C.Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biol Psychiatry 1998;43:348–357.CrossRefGoogle ScholarPubMed
Purcell, R., Maruff, P., Kyrios, M., Pantelis, C.Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls. Arch Gen Psychiatry 1998;55:415–423.CrossRefGoogle ScholarPubMed
Reitan, M., Wolfson, D.The Halstead-Reitan Neuropsychological Test Battery. Tucson: Neuropsychology Press; 1985.Google Scholar
Russell, A.J., Mataix-Cols, D., Anson, M., Murphy, D.G.Obsessions and compulsions in Asperger syndrome and high-functioning autism. Br J Psychiatry 2005;186:525–528.CrossRefGoogle ScholarPubMed
Savage, C.R., Baer, L., Keuthen, N.J., Brown, H.D., Rauch, S.L., Jenike, M.A.Organizational strategies mediate non-verbal memory impairment in obsessive-compulsive disorder. Biol Psychiatry 1999;45:905–916.CrossRefGoogle Scholar
Scarone, S., Colombo, C., Livian, S., Abbruzzese, M., Ronchi, P., Locatelli, M.et al.Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging. Psychiatry Res 1992;45:115–121.CrossRefGoogle ScholarPubMed
Shallice, T.Specific impairments of planning. Philos Trans R Soc Lond B Biol Sci 1982;298:199–209.Google ScholarPubMed
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E.et al.The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:22–33.Google ScholarPubMed
Silverman, J.M., Smith, C.J., Schmeidler, J., Hollander, E., Lawlor, B.A., Fitzgerald, M.et al.Symptom domains in autism and related conditions: evidence for familiarity. Am J Med Genet 2002;114:64–73.CrossRefGoogle Scholar
Spiker, D., Lotspeich, L., Kraemer, H.C., Hallmayer, J., McMahon, W., Petersen, P.B.et al.Genetics of autism: characteristics of affected and unaffected children from 37 multiplex families. Am J Med Genet 1994;54:27–35.CrossRefGoogle ScholarPubMed
Szatmari, P., Jones, M.B., Tuff, L., Bartolucci, G., Fisman, S., Mahoney, W.Lack of cognitive impairment in first-degree relatives of children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 1993;32:1264–1273.CrossRefGoogle ScholarPubMed
Troyer, A.K., Moscovitch, M., Winocur, G., Alexander, M.P., Stuss, D.Clustering and switching on verbal fluency: the effects of focal frontal- and temporal-lobe lesions. Neuropsychologia 1998;36:499–504.CrossRefGoogle ScholarPubMed
Van den Heuvel, O.A., Veltman, D.J., Groenewegen, H.J., Cath, D.C., van Balkom, A.J., van Hartskamp, J.et al.Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Arch Gen Psychiatry 2005;62:301–309.CrossRefGoogle ScholarPubMed
Veale, D.M., Sahakian, B.J., Owen, A.M., Marks, I.M.Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive-compulsive disorder. Psychol Med 1996;26:1261–1269.CrossRefGoogle ScholarPubMed
Welsh, M.C., Labbe, E.E., Delayney, D.Cognitive strategies and personality variables in adherence to exercise. Psychol Rep 1991;68:1327–1335.CrossRefGoogle Scholar
Wilcox, J.A., Tsuang, M.T., Schnurr, T., Baida-Fragoso, N.Case-control family study of lesser variant traits in autism. Neuropsychobiology 2003;47:171–177.CrossRefGoogle ScholarPubMed
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