Abstract
Cognitive dysfunctions such as inhibitory deficits and visuospatial abnormalities are often found in patients with obsessive–compulsive disorder (OCD). Recent findings in unaffected relatives indicate that response inhibition and other neuropsychological functions may also constitute endophenotypes of OCD. In the present study, 30 OCD patients, 30 first-degree relatives, and 30 healthy control subjects were assessed using a comprehensive neuropsychological test battery. A subsample of 21 subjects of each group also performed an antisaccade task. The samples were matched according to age, gender, education, and verbal intelligence. The OCD patients and the unaffected OCD relatives showed increased antisaccade error rates compared with the healthy control group (p = 0.003, p = 0.028, respectively). Significantly prolonged antisaccade latencies as compared to prosaccade latencies were only found in the OCD patients compared with the healthy control group (p = 0.019). Only OCD patients but not the unaffected OCD relatives were impaired with regard to visuospatial functions, problem-solving, and processing speed. Antisaccade errors did not correlate with severity of OCD or depressive symptoms. This study confirms inhibitory deficits, as indicated by increased antisaccade error rates, as a candidate endophenotype of OCD. In agreement with previous findings from imaging studies, our data suggest that functional abnormalities in frontostriatal and parietal cortical regions form part of the vulnerability for OCD.
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References
Abbruzzese M, Ferri S, Scarone S (1997) The selective breakdown of frontal functions in patients with obsessive-compulsive disorder and in patients with schizophrenia: a double dissociation experimental finding. Neuropsychologia 35:907–912
Bannon S, Gonsalvez CJ, Croft RJ, Boyce PM (2002) Response inhibition deficits in obsessive-compulsive disorder. Psychiatry Res 110:165–174
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571
Brown MR, Goltz HC, Vilis T, Ford KA, Everling S (2006) Inhibition and generation of saccades: rapid event-related fMRI of prosaccades, antisaccades, and nogo trials. Neuroimage 33:644–659
Camarena B, Loyzaga C, Aguilar A, Weissbecker K, Nicolini H (2007) Association study between the dopamine receptor D(4) gene and obsessive-compulsive disorder. Eur Neuropsychopharmacol 17:406–409
Cavedini P, Gorini A, Bellodi L (2006) Understanding obsessive-compulsive disorder: focus on decision making. Neuropsychol Rev 16:3–15
Cavedini P, Zorzi C, Piccinni M, Cavallini MC, Bellodi L (2010) Executive dysfunctions in obsessive-compulsive patients and unaffected relatives: searching for a new intermediate phenotype. Biol Psychiatry 67:1178–1184
Chamberlain SR, Blackwell AD, Fineberg NA, Robbins TW, Sahakian BJ (2005) The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neurosci Biobehav Rev 29:399–419
Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ (2006) Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry 163:1282–1284
Chamberlain SR, Fineberg NA, Menzies LA, Blackwell AD, Bullmore ET, Robbins TW, Sahakian BJ (2007) Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. Am J Psychiatry 164:335–338
Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJ (2008) Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science 321:421–422
Deckersbach T, Otto MW, Savage CR, Baer L, Jenike MA (2000) The relationship between semantic organization and memory in obsessive-compulsive disorder. Psychother Psychosom 69:101–107
Delorme R, Gousse V, Roy I, Trandafir A, Mathieu F, Mouren-Simeoni MC, Betancur C, Leboyer M (2007) Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder. Eur Psychiatry 22:32–38
DeSouza JF, Menon RS, Everling S (2003) Preparatory set associated with pro-saccades and anti-saccades in humans investigated with event-related FMRI. J Neurophysiol 89:1016–1023
Ettinger U, Ffytche DH, Kumari V, Kathmann N, Reuter B, Zelaya F, Williams SC (2008) Decomposing the neural correlates of antisaccade eye movements using event-related FMRI. Cereb Cortex 18:1148–1159
Ettinger U, Kumari V, Crawford TJ, Davis RE, Sharma T, Corr PJ (2003) Reliability of smooth pursuit, fixation, and saccadic eye movements. Psychophysiology 40:620–628
Ford KA, Goltz HC, Brown MR, Everling S (2005) Neural processes associated with antisaccade task performance investigated with event-related FMRI. J Neurophysiol 94:429–440
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS (1989) The yale-brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen Psychiatry 46:1006–1011
Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645
Grabe HJ, Ruhrmann S, Ettelt S, Buhtz F, Hochrein A, Schulze-Rauschenbach S, Meyer K, Kraft S, Reck C, Pukrop R, Freyberger HJ, Klosterkotter J, Falkai P, John U, Maier W, Wagner M (2006) Familiality of obsessive-compulsive disorder in nonclinical and clinical subjects. Am J Psychiatry 163:1986–1992
Haraldsson HM, Ettinger U, Magnusdottir BB, Sigmundsson T, Sigurdsson E, Ingason A, Petursson H (2010) Catechol-O-methyltransferase Val 158 Met polymorphism and antisaccade eye movements in schizophrenia. Schizophr Bull 36:157–164
Hutton SB, Ettinger U (2006) The antisaccade task as a research tool in psychopathology: a critical review. Psychophysiology 43:302–313
Kattoulas E, Evdokimidis I, Stefanis NC, Avramopoulos D, Stefanis CN, Smyrnis N (2010) Monitoring antisaccades: inter-individual differences in cognitive control and the influence of COMT and DRD4 genotype variations. Exp Brain Res 203:453–463
Kloft L, Kischkel E, Kathmann N, Reuter B (2011) Evidence for a deficit in volitional action generation in patients with obsessive-compulsive disorder. Psychophysiology 48:755–761
Kuelz AK, Hohagen F, Voderholzer U (2004) Neuropsychological performance in obsessive-compulsive disorder: a critical review. Biol Psychol 65:185–236
Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J (1998) Psychiatric genetics: search for phenotypes. Trends Neurosci 21:102–105
Lehrl S, Merz J, Burkhard G, Fischer S (1989) Mehrfachwahl-Wortschatz-Intelligenztest. Hogrefe Verlag, Göttingen
Malone SM, Iacono WG (2002) Error rate on the antisaccade task: heritability and developmental change in performance among preadolescent and late-adolescent female twin youth. Psychophysiology 39:664–673
Mannuzza S, Fyer AJ, Klein DF, Endicott J (1986) Schedule for affective disorders and schizophrenia–lifetime version modified for the study of anxiety disorders (SADS-LA): rationale and conceptual development. J Psychiatr Res 20:317–325
Maruff P, Purcell R, Tyler P, Pantelis C, Currie J (1999) Abnormalities of internally generated saccades in obsessive-compulsive disorder. Psychol Med 29:1377–1385
Massen C (2004) Parallel programming of exogenous and endogenous components in the antisaccade task. Q J Exp Psychol A 57:475–498
Mataix-Cols D, Rosario-Campos MC, Leckman JF (2005) A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry 162:228–238
McDowell JE, Dyckman KA, Austin BP, Clementz BA (2008) Neurophysiology and neuroanatomy of reflexive and volitional saccades: evidence from studies of humans. Brain Cogn 68:255–270
McDowell JE, Kissler JM, Berg P, Dyckman KA, Gao Y, Rockstroh B, Clementz BA (2005) Electroencephalography/magnetoencephalography study of cortical activities preceding prosaccades and antisaccades. NeuroReport 16:663–668
Menzies L, Achard S, Chamberlain SR, Fineberg N, Chen CH, del Campo N, Sahakian BJ, Robbins TW, Bullmore E (2007) Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain 130:3223–3236
Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET (2008) Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev 32:525–549
Miguel EC, Leckman JF, Rauch S, do Rosario-Campos MC, Hounie AG, Mercadante MT, Chacon P, Pauls DL (2005) Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry 10:258–275
Nestadt G, Samuels J, Riddle M, Bienvenu OJ III, Liang KY, LaBuda M, Walkup J, Grados M, Hoehn-Saric R (2000) A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 57:358–363
Nicolini H, Arnold P, Nestadt G, Lanzagorta N, Kennedy JL (2009) Overview of genetics and obsessive-compulsive disorder. Psychiatry Res 170:7–14
Olley A, Malhi G, Sachdev P (2007) Memory and executive functioning in obsessive-compulsive disorder: a selective review. J Affect Disord 104:15–23
Pauls DL (2008) The genetics of obsessive compulsive disorder: a review of the evidence. Am J Med Genet C Semin Med Genet 148C:133–139
Pauls DL, Alsobrook JP II, Goodman W, Rasmussen S, Leckman JF (1995) A family study of obsessive-compulsive disorder. Am J Psychiatry 152:76–84
Penades R, Catalan R, Rubia K, Andres S, Salamero M, Gasto C (2007) Impaired response inhibition in obsessive compulsive disorder. Eur Psychiatry 22:404–410
Pooley EC, Fineberg N, Harrison PJ (2007) The met(158) allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol Psychiatry 12:556–561
Purcell R, Maruff P, Kyrios M, Pantelis C (1998) Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biol Psychiatry 43:348–357
Purcell R, Maruff P, Kyrios M, Pantelis C (1998) Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls. Arch Gen Psychiatry 55:415–423
Raemaekers M, Jansma JM, Cahn W, Van der Geest JN, van der Linden JA, Kahn RS, Ramsey NF (2002) Neuronal substrate of the saccadic inhibition deficit in schizophrenia investigated with 3-dimensional event-related functional magnetic resonance imaging. Arch Gen Psychiatry 59:313–320
Raemaekers M, Ramsey NF, Vink M, van den Heuvel MP, Kahn RS (2006) Brain activation during antisaccades in unaffected relatives of schizophrenic patients. Biol Psychiatry 59:530–535
Rajender G, Bhatia MS, Kanwal K, Malhotra S, Singh TB, Chaudhary D (2011) Study of neurocognitive endophenotypes in drug-naive obsessive-compulsive disorder patients, their first-degree relatives and healthy controls. Acta Psychiatr Scand 124:152–161
Rampacher F, Lennertz L, Vogeley A, Schulze-Rauschenbach S, Kathmann N, Falkai P, Wagner M (2010) Evidence for specific cognitive deficits in visual information processing in patients with OCD compared to patients with unipolar depression. Prog Neuropsychopharmacol Biol Psychiatry 34:984–991
Reuter B, Kaufmann C, Bender J, Pinkpank T, Kathmann N (2010) Distinct neural correlates for volitional generation and inhibition of saccades. J Cogn Neurosci 22:728–738
Riesel A, Endrass T, Kaufmann C, Kathmann N (2011) Overactive error-related brain activity as a candidate endophenotype for obsessive-compulsive disorder: evidence from unaffected first-degree relatives. Am J Psychiatry 168:317–324
Rosenberg DR, Averbach DH, O’Hearn KM, Seymour AB, Birmaher B, Sweeney JA (1997) Oculomotor response inhibition abnormalities in pediatric obsessive-compulsive disorder. Arch Gen Psychiatry 54:831–838
Rosenberg DR, Dick EL, O’Hearn KM, Sweeney JA (1997) Response-inhibition deficits in obsessive-compulsive disorder: an indicator of dysfunction in frontostriatal circuits. J Psychiatry Neurosci 22:29–38
Rotge JY, Langbour N, Guehl D, Bioulac B, Jaafari N, Allard M, Aouizerate B, Burbaud P (2010) Gray matter alterations in obsessive-compulsive disorder: an anatomic likelihood estimation meta-analysis. Neuropsychopharmacology 35:686–691
Savage CR, Baer L, Keuthen NJ, Brown HD, Rauch SL, Jenike MA (1999) Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder. Biol Psychiatry 45:905–916
Segalas C, Alonso P, Real E, Garcia A, Minambres A, Labad J, Pertusa A, Bueno B, Jimenez-Murcia S, Menchon JM (2010) Memory and strategic processing in first-degree relatives of obsessive compulsive patients. Psychol Med 40:1–11
Spreen O, Strauss E (2006) A compendium of neuropsychological tests. Administration, norms, and commentary, 3rd edn. University Press, Oxford
Szeszko PR, Ardekani BA, Ashtari M, Malhotra AK, Robinson DG, Bilder RM, Lim KO (2005) White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study. Arch Gen Psychiatry 62:782–790
Tien AY, Pearlson GD, Machlin SR, Bylsma FW, Hoehn-Saric R (1992) Oculomotor performance in obsessive-compulsive disorder. Am J Psychiatry 149:641–646
Turetsky BI, Calkins ME, Light GA, Olincy A, Radant AD, Swerdlow NR (2007) Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. Schizophr Bull 33:69–94
van den Heuvel OA, Veltman DJ, Groenewegen HJ, Cath DC, van Balkom AJ, van Hartskamp J, Barkhof F, van Dyck R (2005) Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Arch Gen Psychiatry 62:301–309
van der Wee NJ, Hardeman HH, Ramsey NF, Raemaekers M, Van Megen HJ, Denys DA, Westenberg HG, Kahn RS (2006) Saccadic abnormalities in psychotropic-naive obsessive-compulsive disorder without co-morbidity. Psychol Med 36:1321–1326
van Grootheest DS, Bartels M, van Beijsterveldt CE, Cath DC, Beekman AT, Hudziak JJ, Boomsma DI (2008) Genetic and environmental contributions to self-report obsessive-compulsive symptoms in Dutch adolescents at ages 12, 14, and 16. J Am Acad Child Adolesc Psychiatry 47:1182–1188
Viswanath B, Janardhan Reddy YC, Kumar KJ, Kandavel T, Chandrashekar CR (2009) Cognitive endophenotypes in OCD: a study of unaffected siblings of probands with familial OCD. Prog Neuropsychopharmacol Biol Psychiatry 33:610–615
Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK, Newman SC, Oakley-Browne MA, Rubio-Stipec M, Wickramaratne PJ et al (1994) The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 55(Suppl):5–10
Acknowledgments
The authors like to thank Eveline Matuschek for her assistance in data acquisition. This research work was funded by the Deutsche Forschungsgemeinschaft (DFG). The neuropsychological assessment was a part of a multicentre study entitled “Clinical Heterogeneity and Familiarity of OCD” (Fa 731/6-1) which was conducted at the German university hospitals of Bonn, Cologne, Stralsund, and Homburg; all of which are part of the “German epidemiologic network of OCD studies” (GENOS).
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Lennertz, L., Rampacher, F., Vogeley, A. et al. Antisaccade performance in patients with obsessive–compulsive disorder and unaffected relatives: further evidence for impaired response inhibition as a candidate endophenotype. Eur Arch Psychiatry Clin Neurosci 262, 625–634 (2012). https://doi.org/10.1007/s00406-012-0311-1
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DOI: https://doi.org/10.1007/s00406-012-0311-1