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Meta-analysis of neurocognitive deficits in unaffected relatives of obsessive-compulsive disorder (OCD): comparison with healthy controls and patients with OCD

Published online by Cambridge University Press:  01 June 2020

Emre Bora*
Affiliation:
Department of Psychiatry, Dokuz Eylul University Medical School, Izmir35340, Turkey Department of Neuroscience, Dokuz Eylul University, Izmir35340, Turkey Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, Victoria3053, Australia
*
Author for correspondence: Emre Bora, E-mail: emre.bora@deu.edu.tr, ibora@unimelb.edu.au

Abstract

Background

Obsessive-compulsive disorder (OCD) has been associated with cognitive deficits, particularly with executive functions. These findings support fronto-striatal dysfunction in OCD. However, it is not certain whether these findings are trait features of OCD. In recent years, a number of studies have investigated cognitive functions in unaffected relatives of OCD (OCDrel) but the findings of these studies are contradictory.

Methods

A systematic review in Pubmed and Scopus databases was performed until 18 March 2019, to locate the studies comparing cognitive functions of OCDrel with healthy controls and OCD patients (OCDpt). A random-effects meta-analysis was conducted.

Results

Current meta-analysis included 16 studies including 527 OCDrel, 445 OCDpt and 639 healthy controls. Healthy controls overperformed OCDpt in all cognitive domains (d = 0.36–0.86). OCDrel underperformed healthy controls in inhibition (d = 0.58, CI = 0.29–0.86), planning (d = 0.45, CI = 0.28–0.63), decision-making (d = 0.58, CI = 0.19–0.98). OCDrel also had small-sized deficits in set-shifting (d = 0.37, CI = 0.04–0.69) and visual memory (d = 0.28, CI = 0.08–0.49). OCDpt underperformed OCDrel in visual memory (d = 0.45, CI = 0.22–0.67) and set-shifting (d = 0.23, CI = 0.04–0.42).

Conclusions

Current findings suggest that abnormalities in inhibition, planning/problem solving and reward-based decision-making are shared features of OCDrel and OCDpt and might be trait markers related to vulnerability for developing OCD. Visual memory and set-shifting deficits might potentially be biomarkers of incipient illness or subthreshold OCD presentation among OCDrel. Further exploration of cognitive heterogeneity in OCDrel and investigating the effects of the subtypes of OCD in probands on cognitive impairment in OCDrel are needed.

Type
Review Article
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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References

Abramovitch, A., Abramowitz, J. S., & Mittelman, A. (2013). The neuropsychology of adult obsessive-compulsive disorder: A meta-analysis. Clinical Psychology Review, 33, 11631171.CrossRefGoogle ScholarPubMed
Abramovitch, A., & Cooperman, A. (2015). The cognitive neuropsychology of obsessive-compulsive disorder: A critical review. Journal of Obsessive-Compulsive and Related Disorders, 5, 2436.CrossRefGoogle Scholar
Abramovitch, A., McCormack, B., Brunner, D., Johnson, M., & Wofford, N. (2019). The impact of symptom severity on cognitive function in obsessive-compulsive disorder: A meta-analysis. Clinical Psychology Review, 67, 3644.CrossRefGoogle ScholarPubMed
Arnold, P. D., Askland, K. D., Barlassina, C., Bellodi, L., Bienvenu, O. J., Black, D., … Zai, G. (2018). Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis. Molecular Psychiatry, 23, 11811188.Google Scholar
Bey, K., Kaufmann, C., Lennertz, L., Riesel, A., Klawohn, J., Heinzel, S., … Wagner, M. (2018). Impaired planning in patients with obsessive-compulsive disorder and unaffected first-degree relatives: Evidence for a cognitive endophenotype. Journal of Anxiety Disorders, 57, 2430.CrossRefGoogle ScholarPubMed
Blanes, T., & McGuire, P. (1997). Heterogeneity within obsessive–compulsive disorder: Evidence for primary and neurodevelopmental subtypes. In Keshavan, M. S. & Murray, R. M. (eds.), Neurodevelopment and adult psychopathology (pp. 206212). Cambridge, UK: Cambridge University Press.Google Scholar
Bora, E. (2015). Neurodevelopmental origin of cognitive impairment in schizophrenia. Psychological Medicine, 45, 19.CrossRefGoogle Scholar
Bora, E. (2017). A comparative meta-analysis of neurocognition in first-degree relatives of patients with schizophrenia and bipolar disorder. European Psychiatry, 45, 121128.CrossRefGoogle ScholarPubMed
Bortolato, B., Miskowiak, K. W., Köhler, C. A., Vieta, E., & Carvalho, A. F. (2015). Cognitive dysfunction in bipolar disorder and schizophrenia: A systematic review of meta-analyses. Neuropsychiatric Disease and Treatment, 11, 31113125.Google ScholarPubMed
Bragdon, L. B., Gibb, B. E., & Coles, M. E. (2018). Does neuropsychological performance in OCD relate to different symptoms? A meta-analysis comparing the symmetry and obsessing dimensions. Depression and Anxiety, 35, 761774.CrossRefGoogle ScholarPubMed
Castle, D. J., & Phillips, K. A. (2006). Obsessive-compulsive spectrum of disorders: A defensible construct? Australian & New Zealand Journal of Psychiatry, 40, 114120.Google ScholarPubMed
Cavedini, P., Zorzi, C., Piccinni, M., Cavallini, M. C., & Bellodi, L. (2010). Executive dysfunctions in obsessive-compulsive patients and unaffected relatives: Searching for a new intermediate phenotype. Biological Psychiatry, 67, 11781184.CrossRefGoogle ScholarPubMed
Chamberlain, S. R., Blackwell, A. D., Fineberg, N. A., Robbins, T. W., & Sahakian, B. J. (2005). The neuropsychology of obsessive compulsive disorder: The importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neuroscience and Biobehavioral Reviews, 29, 399419.CrossRefGoogle ScholarPubMed
Chamberlain, S. R., Fineberg, N. A., Menzies, L. A., Blackwell, A. D., Bullmore, E. T., Robbins, T. W., & Sahakian, B. J. (2007). Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. American Journal of Psychiatry, 164, 335338.CrossRefGoogle ScholarPubMed
Delorme, R., Goussé, V., Roy, I., Trandafir, A., Mathieu, F., Mouren-Siméoni, M. C., … Leboyer, M. (2007). Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder. European Psychiatry, 22, 3238.CrossRefGoogle ScholarPubMed
den Braber, A., Zilhão, N. R., Fedko, I. O., Hottenga, J. J., Pool, R., Smit, D. J., … Boomsba, D. I. (2016). Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs. Translational Psychiatry, 6, e731.CrossRefGoogle Scholar
de Vries, F. E., de Wit, S. J., Cath, D. C., van der Werf, Y. D., van der Borden, V., van Rossum, T. B., … van den Heuvel, O. A. (2014). Compensatory frontoparietal activity during working memory: An endophenotype of obsessive-compulsive disorder. Biological Psychiatry, 76, 878887.CrossRefGoogle ScholarPubMed
de Wit, S. J., de Vries, F. E., van der Werf, Y. D., Cath, D. C., Heslenfeld, D. J., Veltman, E. M., … van den Heuvel, O. A. (2012). Presupplementary motor area hyperactivity during response inhibition: A candidate endophenotype of obsessive-compulsive disorder. American Journal of Psychiatry, 169, 11001108.CrossRefGoogle ScholarPubMed
Fan, J., Liu, W., Lei, H., Cai, L., Zhong, M., Dong, J., … Zhu, X. (2016). Components of inhibition in autogenous- and reactive-type obsessive-compulsive disorder: Dissociation of interference control. Biological Psychology, 117, 117130.CrossRefGoogle ScholarPubMed
Figee, M., Pattij, T., Willuhn, I., Luigjes, J., van den Brink, W., Goudriaan, A., … Denys, D. (2016). Compulsivity in obsessive-compulsive disorder and addictions. European Neuropsychopharmacology, 26, 856868.CrossRefGoogle ScholarPubMed
Fouche, J. P., du Plessis, S., Hattingh, C., Roos, A., Lochner, C., Soriano-Mas, C., … van den Heuvel, O. A. (2017). Cortical thickness in obsessive-compulsive disorder: Multisite mega-analysis of 780 brain scans from six centres. The British Journal of Psychiatry, 210, 6774.CrossRefGoogle ScholarPubMed
Frost, R. O., & Steketee, G. (1997). Perfectionism in obsessive-compulsive disorder patients. Behavioral Research and Therapy, 35, 291296.CrossRefGoogle ScholarPubMed
Furukawa, T. A., Reijnders, M., Kishimoto, S., Sakata, M., DeRubeis, R. J., Dimidjian, S., … Cuijpers, P. (2019). Translating the BDI and BDI-II into the HAMD and vice versa with equipercentile linking. Epidemiology and Psychiatric Sciences, 29, e24.CrossRefGoogle ScholarPubMed
Gillan, C. M., Fineberg, N. A., & Robbins, T. W. (2017). A trans-diagnostic perspective on obsessive-compulsive disorder. Psychological Medicine, 47, 15281548.CrossRefGoogle ScholarPubMed
Gonçalves, ÓF, Soares, J. M., Carvalho, S., Leite, J., Ganho-Ávila, A., Fernandes-Gonçalves, A., … Sampaio, A. (2017). Patterns of default mode network deactivation in obsessive compulsive disorder. Scientific Reports, 7, 44468.CrossRefGoogle ScholarPubMed
Gürsel, D. A., Avram, M., Sorg, C., Brandl, F., & Koch, K. (2018). Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: A meta-analysis of resting-state functional connectivity. Neuroscience & Biobehavioral Reviews, 87, 151160.CrossRefGoogle ScholarPubMed
Harrison, B. J., Soriano-Mas, C., Pujol, J., Ortiz, H., López-Solà, M., Hernández-Ribas, R., … Cardoner, N. (2009). Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Archives of General Psychiatry, 66, 11891200.CrossRefGoogle ScholarPubMed
Hauser, T. U., Iannaccone, R., Dolan, R. J., Ball, J., Hättenschwiler, J., Drechsler, R., … Brem, S. (2017). Increased fronto-striatal reward prediction errors moderate decision making in obsessive-compulsive disorder. Psychological Medicine, 47, 12461258.CrossRefGoogle ScholarPubMed
Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., … Wang, P. (2010). Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167, 748751.CrossRefGoogle Scholar
Karno, M., Golding, J. M., Sorenson, S. B., & Burnam, M. A. (1988). The epidemiology of obsessive-compulsive disorder in five US communities. Archives Of General Psychiatry, 45, 10941099.CrossRefGoogle ScholarPubMed
Kloft, L., Steinel, T., & Kathmann, N. (2018). Systematic review of co-occurring OCD and TD: Evidence for a tic-related OCD subtype? Neuroscience & Biobehavioral Reviews, 95, 280314.CrossRefGoogle ScholarPubMed
Koçak, O., Özpolat, A., Atbaşoğlu, C., & Çiçek, M. (2011). Cognitive control of a simple mental image in patients with obsessive–compulsive disorder. Brain and Cognition, 76, 390399.CrossRefGoogle ScholarPubMed
Leckman, J. F., Bloch, M. H., & King, R. A. (2009). Symptom dimensions and subtypes of obsessive-compulsive disorder: A developmental perspective. Dialogues in Clinical Neuroscience, 11, 2133.Google ScholarPubMed
Lee, H. J., Yost, B. P., & Telch, M. J. (2009). Differential performance on the go/no-go task as a function of the autogenous-reactive taxonomy of obsessions: Findings from a non-treatment seeking sample. Behaviour Research and Therapy, 47, 294300.CrossRefGoogle ScholarPubMed
Lennertz, L., Rampacher, F., Vogeley, A., Schulze-Rauschenbach, S., Pukrop, R., Ruhrmann, S., … Wagner, M. (2012). Antisaccade performance in patients with obsessive-compulsive disorder and unaffected relatives: Further evidence for impaired response inhibition as a candidate endophenotype. European Archives of Psychiatry and Clinical Neuroscience, 262, 625634.CrossRefGoogle ScholarPubMed
Leucht, S., Fennema, H., Engel, R. R., Kaspers-Janssen, M., & Szegedi, A. (2018). Translating the HAM-D into the MADRS and vice versa with equipercentile linking. Journal of Affective Disorders, 226, 326331.CrossRefGoogle ScholarPubMed
Li, B., Sun, J. H., Li, T., & Yang, Y. C. (2012). Neuropsychological study of patients with obsessive-compulsive disorder and their parents in China: Searching for potential endophenotypes. Neuroscience Bulletin, 28, 475482.CrossRefGoogle ScholarPubMed
Lochner, C., Chamberlain, S. R., Kidd, M., Fineberg, N. A., & Stein, D. J. (2016). Altered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorder. Psychopharmacology (Berl), 233, 883891.CrossRefGoogle ScholarPubMed
Mathews, C. A., Delucchi, K., Cath, D. C., Willemsen, G., & Boomsma, D. I. (2014). Partitioning the etiology of hoarding and obsessive-compulsive symptoms. Psychological Medicine, 44, 28672876.CrossRefGoogle ScholarPubMed
Menzies, L., Achard, S., Chamberlain, S. R., Fineberg, N., Chen, C., Del Campo, D., & Bullmore, E. (2007). Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain, 130, 32233236. doi:10.1093/brain/awm205CrossRefGoogle ScholarPubMed
Menzies, L., Chamberlain, S. R., Laird, A. R., Thelen, S. M., Sahakian, B. J., & Bullmore, E. T. (2008). Integrating evidence from neuroimaging and neuropsychological studies of obsessive–compulsive disorder: The orbitofronto-striatal model revisited. Neuroscience and Biobehavioral Reviews, 32, 525549.CrossRefGoogle ScholarPubMed
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. The BMJ, 339, b2535.CrossRefGoogle ScholarPubMed
Morein-Zamir, S., Voon, V., Dodds, C. M., Sule, A., van Niekerk, J., Sahakian, B. J., & Robbins, T. W. (2016). Divergent subcortical activity for distinct executive functions: Stopping and shifting in obsessive compulsive disorder. Psychological Medicine, 46, 829840.CrossRefGoogle ScholarPubMed
Norman, L. J., Carlisi, C. O., Christakou, A., Murphy, C. M., Chantiluke, K., Giampietro, V., … Rubia, K. (2018). Frontostriatal dysfunction during decision making in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 3, 694703.Google ScholarPubMed
Norman, L. J., Taylor, S. F., Liu, Y., Radua, J., Chye, Y., De Wit, S. J., … Fitzgerald, K. (2019). Error processing and inhibitory control in obsessive-compulsive disorder: A meta-analysis using statistical parametric maps. Biological Psychiatry, 85, 713725.CrossRefGoogle ScholarPubMed
Ozcan, H., Ozer, S., & Yagcioglu, S. (2016). Neuropsychological, electrophysiological and neurological impairments in patients with obsessive compulsive disorder, their healthy siblings and healthy controls: Identifying potential endophenotype(s). Psychiatry Research, 240, 110117.CrossRefGoogle Scholar
Purcell, R., Maruff, P., Kyrios, M., & Pantelis, C. (1998). Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal function. Biological Psychiatry, 43, 348357.CrossRefGoogle ScholarPubMed
Rajender, G., Bhatia, M. S., Kanwal, K., Malhotra, S., Singh, T. B., & Chaudhary, D. (2011). Study of neurocognitive endophenotypes in drug-naïve obsessive-compulsive disorder patients, their first-degree relatives and healthy controls. Acta Psychiatrica Scandinavica, 124, 152161.CrossRefGoogle ScholarPubMed
Rasgon, A., Lee, W. H., Leibu, E., Laird, A., Glahn, D., Goodman, W., & Frangou, S. (2017). Neural correlates of affective and non-affective cognition in obsessive compulsive disorder: A meta-analysis of functional imaging studies. European Psychiatry, 46, 2532.CrossRefGoogle ScholarPubMed
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. American Journal of Psychiatry, 168, 317324.CrossRefGoogle ScholarPubMed
Riesel, A., Klawohn, J., Grützmann, R., Kaufmann, C., Heinzel, S., Bey, K., … Kathmann, N. (2019). Error-related brain activity as a transdiagnostic endophenotype for obsessive-compulsive disorder, anxiety and substance use disorder. Psychological Medicine, 12, 111.Google Scholar
Saxena, S., Brody, A. L., Schwartz, J. M., & Baxter, L. R. (1998). Neuroimaging and frontal–subcortical circuitry in obsessive–compulsive disorder. British Journal of Psychiatry, 173, 2637.CrossRefGoogle Scholar
Segalàs, C., Alonso, P., Real, E., Garcia, A., Miñambres, A., Labad, J., … Menchón, J. M. (2010). Memory and strategic processing in first-degree relatives of obsessive compulsive patients. Psychological Medicine, 40, 20012011.CrossRefGoogle ScholarPubMed
Shin, N. Y., Lee, T. Y., Kim, E., & Kwon, J. S. (2014). Cognitive functioning in obsessive-compulsive disorder: A meta-analysis. Psychological Medicine, 44, 11211130.CrossRefGoogle ScholarPubMed
Snyder, H. R., Kaiser, R. H., Warren, S. L., & Heller, W. (2015). Obsessive-compulsive disorder is associated with broad impairments in executive function: A meta-analysis. Clinical Psychological Science, 3, 301330.CrossRefGoogle ScholarPubMed
Stern, E. R., Fitzgerald, K. D., Welsh, R. C., Abelson, J. L., & Taylor, S. F. (2012). Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder. PLOS ONE, 7, e36356.CrossRefGoogle ScholarPubMed
Vaghi, M. M., Hampshire, A., Fineberg, N. A., Kaser, M., Brühl, A. B., Sahakian, B. J., … Robbins, T. W. (2017). Hypoactivation and dysconnectivity of a frontostriatal circuit during goal-directed planning as an endophenotype for obsessive-compulsive disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2, 655663.Google ScholarPubMed
van den Heuvel, O. A., Veltman, D. J., Groenewegen, H. J., Cath, D. C., van Balkom, A. J., van Hartskamp, J., … van Dyck, R. (2005). Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Archives of General Psychiatry, 62, 301309.CrossRefGoogle ScholarPubMed
van Grootheest, D. S., Cath, D. C., Beekman, A. T., & Boomsma, D. I. (2005). Twin studies on obsessive-compulsive disorder: A review. Twin Research and Human Genetics, 8, 450458.CrossRefGoogle ScholarPubMed
Viechtbauer, W. (2010). Conducting meta-analyses in R with the metafor package. Journal of Statistical Software, 36, 148.CrossRefGoogle Scholar
Viswanath, B., Janardhan Reddy, Y. C., Kumar, K. J., Kandavel, T., & Chandrashekar, C. R. (2009). Cognitive endophenotypes in OCD: A study of unaffected siblings of probands with familial OCD. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 33, 610615.CrossRefGoogle ScholarPubMed
Weissman, M. M., Bland, R. C., Canino, G. J., Greenwald, S., Hwu, H. G., Lee, C. K., … Wickramaratne, P. J. (1994). The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. Journal of Clinical Psychiatry, 55, 510.Google ScholarPubMed
Zhang, L., Dong, Y., Ji, Y., Zhu, C., Yu, F., Ma, H., … Wang, K. (2015 b). Dissociation of decision making under ambiguity and decision making under risk: A neurocognitive endophenotype candidate for obsessive-compulsive disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 57, 6068.CrossRefGoogle ScholarPubMed
Zhang, J., Yang, X., & Yang, Q. (2015 a). Neuropsychological dysfunction in adults with early-onset obsessive-compulsive disorder: The search for a cognitive endophenotype. Brazilian Journal of Psychiatry, 37, 126132.CrossRefGoogle ScholarPubMed
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