Abstract
Little is known about the underlying neurobiological mechanisms in patients with obsessive-compulsive disorder (OCD). We aimed to examine cortical thickness and surface area in individuals with OCD and their unaffected siblings, comparing them to healthy controls. 30 patients with OCD, 21 unaffected siblings (SIB) and 30 controls underwent structural magnetic resonance imaging. Structural images were analyzed using the FreeSurfer software package (version 6.0). Compared to healthy controls, both OCD and SIB groups showed significantly lower cortical thickness in the right anterior insula. Surface areas of the superior frontal gyrus, paracentral gyrus and precuneus of the right hemisphere were also reduced in OCD patients compared to controls. There were no significant differences in cortical thickness and surface area between the OCD and SIB groups. We did not detect any significant differences in subcortical volumes between groups. Lower cortical thickness in the right anterior insula in both OCD patients and unaffected siblings may represent a potential structural endophenotype for OCD.
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References
Beck, A. T., Steer, R. A., & Carbin, M. G. (1988). Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation. Clinical Psychology Review, 8(1), 77–100
Boedhoe, P. S., Schmaal, L., Abe, Y., Ameis, S. H., Arnold, P. D., Batistuzzo, M. C., et al. (2017). Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis. American Journal of Psychiatry, 174(1), 60–69. https://doi.org/10.1176/appi.ajp.2016.16020201
Boedhoe, P. S. W., Schmaal, L., Abe, Y., Alonso, P., Ameis, S. H., Anticevic, A., et al. (2018). Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group. American Journal of Psychiatry, 175(5), 453–462. https://doi.org/10.1176/appi.ajp.2017.17050485
Bora, E. (2020). Meta-analysis of neurocognitive deficits in unaffected relatives of obsessive-compulsive disorder (OCD): comparison with healthy controls and patients with OCD. Psychological Medicine, 50(8), 1257–1266. https://doi.org/10.1017/S0033291720001634
Cai, W., Ryali, S., Chen, T., Li, C. S., & Menon, V. (2014). Dissociable roles of right inferior frontal cortex and anterior insula in inhibitory control: evidence from intrinsic and task-related functional parcellation, connectivity, and response profile analyses across multiple datasets. Journal of Neuroscience, 34(44), 14652–14667. https://doi.org/10.1523/JNEUROSCI.3048-14.2014
Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage, 9(2), 179–194. https://doi.org/10.1006/nimg.1998.0395
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(10), 1100–1108. https://doi.org/10.1176/appi.ajp.2012.12010073
de Wit, S. J., Alonso, P., Schweren, L., Mataix-Cols, D., Lochner, C., Menchon, J. M., et al. (2014). Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive- compulsive disorder. American Journal of Psychiatry, 171(3), 340–349. https://doi.org/10.1176/appi.ajp.2013.13040574
Dikmeer, N., Besiroglu, L., Di Biase, M. A., Zalesky, A., Kasal, M. I., Bilge, A. … Zorlu, N. (2021). White matter microstructure and connectivity in patients with obsessive-compulsive disorder and their unaffected siblings. Acta Psychiatrica Scandinavica, 143, 72–81. https://doi.org/10.1111/acps.13241
Dosenbach, N. U., Fair, D. A., Miezin, F. M., Cohen, A. L., Wenger, K. K., Dosenbach, R. A. … Petersen, S. E. (2007). Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences, 104(26), 11073–11078. https://doi.org/10.1073/pnas.0704320104
Draper, A., Jackson, G. M., Morgan, P. S., & Jackson, S. R. (2016). Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome. Journal of Neuropsychology, 10(1), 143–153. https://doi.org/10.1111/jnp.12089
Eng, G. K., Sim, K., & Chen, S. H. A. (2015). Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review. Neuroscience & Biobehavioral Reviews, 52, 233–257. https://doi.org/10.1016/j.neubiorev.2015.03.002
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1996). Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Clinician Version: Administration Booklet. American Psychiatric Association Publishing
Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage, 9(2), 195–207. https://doi.org/10.1006/nimg.1998.0396
Fischl, B., & Dale, A. M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences, 97(20), 11050–11055. https://doi.org/10.1073/pnas.200033797
Fouche, J. P., du Plessis, S., Hattingh, C., Roos, A., Lochner, C., Soriano-Mas, C., et al. (2017). Cortical thickness in obsessive-compulsive disorder: multisite mega-analysis of 780 brain scans from six centres. The British Journal of Psychiatry, 210(1), 67–74. https://doi.org/10.1192/bjp.bp.115.164020
Gomes, P. V., Brasil-Neto, J. P., Allam, N., & de Rodrigues, E. (2012). A randomized, double- blind trial of repetitive transcranial magnetic stimulation in obsessive-compulsive disorder with three-month follow-up. The Journal of Neuropsychiatry and Clinical Neurosciences, 24(4), 437–443. https://doi.org/10.1176/appi.neuropsych.11100242
Goodkind, M., Eickhoff, S. B., Oathes, D. J., Jiang, Y., Chang, A., Jones-Hagata, L. B. … Etkin, A. (2015). Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry, 72(4), 305–315. https://doi.org/10.1001/jamapsychiatry.2014.2206
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American journal of psychiatry, 160(4), 636–645
Hagler, D. J. Jr., Saygin, A. P., & Sereno, M. I. (2006). Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data. Neuroimage, 33(4), 1093–1103. https://doi.org/10.1016/j.neuroimage.2006.07.036
Hawken, E. R., Dilkov, D., Kaludiev, E., Simek, S., Zhang, F., & Milev, R. (2016). Transcranial Magnetic Stimulation of the Supplementary Motor Area in the Treatment of Obsessive- Compulsive Disorder: A Multi-Site Study. International Journal of Molecular Sciences, 17(3), 420. https://doi.org/10.3390/ijms17030420
Hollander, E., Stein, D. J., Fineberg, N. A., Marteau, F., & Legault, M. (2010). Quality of life outcomes in patients with obsessive-compulsive disorder: relationship to treatment response and symptom relapse. The Journal of Clinical Psychiatry, 71(6), 784–792. https://doi.org/10.4088/JCP.09m05911blu
Huggins, A. A., Harvey, A. M., Miskovich, T. A., Lee, H. J., & Larson, C. L. (2020). Resting-State Functional Connectivity of Supplementary Motor Area Associated with Skin-Picking Symptom Severity. Journal of Obsessive-Compulsive and Related Disorders, 26, 100551. https://doi.org/10.1016/j.jocrd.2020.100551
Jiang, J., Beck, J., Heller, K., & Egner, T. (2015). An insula-frontostriatal network mediates flexible cognitive control by adaptively predicting changing control demands. Nature Communications, 6, 8165. https://doi.org/10.1038/ncomms9165
Kuhn, S., Kaufmann, C., Simon, D., Endrass, T., Gallinat, J., & Kathmann, N. (2013). Reduced thickness of anterior cingulate cortex in obsessive-compulsive disorder. Cortex, 49(8), 2178–2185. https://doi.org/10.1016/j.cortex.2012.09.001
Mantovani, A., Simpson, H. B., Fallon, B. A., Rossi, S., & Lisanby, S. H. (2010). Randomized sham- controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive- compulsive disorder. International Journal of Neuropsychopharmacology, 13(2), 217–227. https://doi.org/10.1017/S1461145709990435
Mataix-Cols, D., Boman, M., Monzani, B., Ruck, C., Serlachius, E., Langstrom, N., & Lichtenstein, P. (2013). Population-based, multigenerational family clustering study of obsessive-compulsive disorder. JAMA Psychiatry, 70(7), 709–717. https://doi.org/10.1001/jamapsychiatry.2013.3
Nachev, P., Kennard, C., & Husain, M. (2008). Functional role of the supplementary and pre- supplementary motor areas. Nature Reviews Neuroscience, 9(11), 856–869. https://doi.org/10.1038/nrn2478
Nakamae, T., Narumoto, J., Sakai, Y., Nishida, S., Yamada, K., Kubota, M. … Fukui, K. (2012). Reduced cortical thickness in non-medicated patients with obsessive-compulsive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 37(1), 90–95. https://doi.org/10.1016/j.pnpbp.2012.01.001
Norman, L. J., Carlisi, C. O., Christakou, A., Cubillo, A., Murphy, C. M., Chantiluke, K. … Rubia, K. (2017). Shared and disorder-specific task-positive and default mode network dysfunctions during sustained attention in paediatric Attention-Deficit/Hyperactivity Disorder and obsessive/compulsive disorder. Neuroimage Clinical, 15, 181–193. https://doi.org/10.1016/j.nicl.2017.04.013
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(9), 713–725. https://doi.org/10.1016/j.biopsych.2018.11.010
Northoff, G., Heinzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J. (2006). Self-referential processing in our brain–a meta-analysis of imaging studies on the self. Neuroimage, 31(1), 440–457. https://doi.org/10.1016/j.neuroimage.2005.12.002
Page, L. A., Rubia, K., Deeley, Q., Daly, E., Toal, F., Mataix-Cols, D. … Murphy, D. G. (2009). A functional magnetic resonance imaging study of inhibitory control in obsessive-compulsive disorder. Psychiatry Research: Neuroimaging, 174(3), 202–209. https://doi.org/10.1016/j.pscychresns.2009.05.002
Pauls, D. L., Abramovitch, A., Rauch, S. L., & Geller, D. A. (2014). Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nature Reviews Neuroscience, 15(6), 410–424. https://doi.org/10.1038/nrn3746
Piras, F., Piras, F., Chiapponi, C., Girardi, P., Caltagirone, C., & Spalletta, G. (2015). Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies. Cortex, 62, 89–108. https://doi.org/10.1016/j.cortex.2013.01.016
Preuschoff, K., Quartz, S. R., & Bossaerts, P. (2008). Human insula activation reflects risk prediction errors as well as risk. Journal of Neuroscience, 28(11), 2745–2752
Radua, J., & Mataix-Cols, D. (2009). Voxel-wise meta-analysis of grey matter changes in obsessive- compulsive disorder. The British Journal of Psychiatry, 195(5), 393–402. https://doi.org/10.1192/bjp.bp.108.055046
Radua, J., van den Heuvel, O. A., Surguladze, S., & Mataix-Cols, D. (2010). Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder vs other anxiety disorders. Archives of General Psychiatry, 67(7), 701–711
Raichle, M. E. (2015). The brain’s default mode network. Annual Review of Neuroscience, 38, 433–447. https://doi.org/10.1146/annurev-neuro-071013-014030
Rakic, P. (2004). Neuroscience. Genetic control of cortical convolutions. Science, 303(5666), 1983–1984. https://doi.org/10.1126/science.1096414
Robbins, T. W., Vaghi, M. M., & Banca, P. (2019). Obsessive-Compulsive Disorder: Puzzles and Prospects. Neuron, 102(1), 27–47. https://doi.org/10.1016/j.neuron.2019.01.046
Rosario-Campos, M. C., Miguel, E. C., Quatrano, S., Chacon, P., Ferrao, Y., Findley, D. … Leckman, J. F. (2006). The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS): an instrument for assessing obsessive-compulsive symptom dimensions. Molecular Psychiatry, 11(5), 495–504. https://doi.org/10.1038/sj.mp.4001798
Rotge, J. Y., Langbour, N., Guehl, D., Bioulac, B., Jaafari, N., Allard, M. … Burbaud, P. (2010). Gray matter alterations in obsessive-compulsive disorder: an anatomic likelihood estimation meta-analysis. Neuropsychopharmacology, 35(3), 686–691. https://doi.org/10.1038/npp.2009.175
Rus, O. G., Reess, T. J., Wagner, G., Zaudig, M., Zimmer, C., & Koch, K. (2017). Structural alterations in patients with obsessive-compulsive disorder: a surface-based analysis of cortical volume, surface area and thickness. Journal of Psychiatry & Neuroscience, 42(6), 395–403. https://www.ncbi.nlm.nih.gov/pubmed/28832321
Ruscio, A. M., Stein, D. J., Chiu, W. T., & Kessler, R. C. (2010). The epidemiology of obsessive- compulsive disorder in the National Comorbidity Survey Replication. Molecular Psychiatry, 15(1), 53–63. https://doi.org/10.1038/mp.2008.94
Shaw, P., Sharp, W., Sudre, G., Wharton, A., Greenstein, D., Raznahan, A. … Rapoport, J. (2015). Subcortical and cortical morphological anomalies as an endophenotype in obsessive-compulsive disorder. Molecular Psychiatry, 20(2), 224–231
Stein, D. J., Costa, D. L. C., Lochner, C., Miguel, E. C., Reddy, Y. C. J., Shavitt, R. G. … Simpson, H. B. (2019). Obsessive-compulsive disorder. Nature Reviews Disease Primers, 5(1), 52. https://doi.org/10.1038/s41572-019-0102-3
Subira, M., Alonso, P., Segalas, C., Real, E., Lopez-Sola, C., Pujol, J. … Soriano-Mas, C. (2013). Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions. PLoS One, 8(9), e75273. https://doi.org/10.1371/journal.pone.0075273
Subira, M., Sato, J. R., Alonso, P., do Rosario, M. C., Segalas, C., Batistuzzo, M. C. … Soriano-Mas, C. (2015). Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder. Journal of Psychiatry & Neuroscience, 40(4), 232–240. https://doi.org/10.1503/jpn.140118
Venkatasubramanian, G., Zutshi, A., Jindal, S., Srikanth, S. G., Kovoor, J. M., Kumar, J. K., & Reddy, Y. C. (2012). Comprehensive evaluation of cortical structure abnormalities in drug-naive, adult patients with obsessive-compulsive disorder: a surface-based morphometry study. Journal of Psychiatric Research, 46(9), 1161–1168. https://doi.org/10.1016/j.jpsychires.2012.06.003
Wagner, G., Kohler, S., Peikert, G., de la Cruz, F., Reess, T. J., Rus, O. G. … Bar, K. J. (2019). Checking and washing rituals are reflected in altered cortical thickness in obsessive-compulsive disorder. Cortex, 117, 147–156. https://doi.org/10.1016/j.cortex.2019.03.012
Winkler, A. M., Kochunov, P., Blangero, J., Almasy, L., Zilles, K., Fox, P. T. … Glahn, D. C. (2010). Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies. Neuroimage, 53(3), 1135–1146. https://doi.org/10.1016/j.neuroimage.2009.12.028
Zhou, C., Xu, J., Ping, L., Zhang, F., Chen, W., Shen, Z. … Cheng, Y. (2018). Cortical thickness and white matter integrity abnormalities in obsessive-compulsive disorder: A combined multimodal surface-based morphometry and tract-based spatial statistics study. Depression and Anxiety, 35(8), 742–751. https://doi.org/10.1002/da.22758
Zorlu, N., Cropley, V. L., Zorlu, P. K., Delibas, D. H., Adibelli, Z. H., Baskin, E. P. … Pantelis, C. (2017). Effects of cigarette smoking on cortical thickness in major depressive disorder. Journal of Psychiatric Research, 84, 1–8. https://doi.org/10.1016/j.jpsychires.2016.09.009
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This work was supported by Research Fund of Izmir Katip Celebi University (Project number: 2016-GAP-TIPF-0024) which had no role in the design of the study, collection and analysis of data and decision to publish.
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NZ, ND, MK and LB made substantial contributions to the conception and the design of the work. FG, ED, AB and SP substantively helped with the data acquisition. NZ and ZK made substantial contributions to the analysis and interpretation of the data. LB, NZ and AZ have substantively revised the work.
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Besiroglu, L., Zalesky, A., Kasal, M.I. et al. Cortical thickness and surface area in patients with obsessive compulsive disorder and their unaffected siblings. Brain Imaging and Behavior 16, 1946–1953 (2022). https://doi.org/10.1007/s11682-022-00660-7
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DOI: https://doi.org/10.1007/s11682-022-00660-7