Cited by 400Obsessive-Compulsive Spectrum DisordersAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesPsychoanalysis and Psychopathology Research

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Meta-analytical Comparison of Voxel-Based Morphometry Studies in Obsessive-Compulsive Disorder vs Other Anxiety Disorders

Radua, Joaquim, van den Heuvel, Odile A., Surguladze, Simon, Mataix-Cols, David·2010·Archives of General Psychiatry

DOI 10.1001/archgenpsychiatry.2010.70

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Abstract

CONTEXT: Whether obsessive-compulsive disorder (OCD) is adequately classified as an anxiety disorder is a matter of considerable debate. OBJECTIVES: To quantitatively compare structural brain changes in OCD and other anxiety disorders using novel voxel-based meta-analytical methods and to generate an online database to facilitate replication and further analyses by other researchers. DATA SOURCES: The PubMed, ScienceDirect, and Scopus databases were searched between 2001 (the date of the first voxel-based morphometry study in any anxiety disorder) and 2009. All voxel-based morphometry studies comparing patients with any anxiety disorder and healthy controls were retrieved. Manual searches were also conducted. Authors were contacted soliciting additional data. STUDY SELECTION: Thirty-seven data sets were identified, of which 26 (including 639 patients with anxiety disorders and 737 healthy controls) met inclusion criteria. DATA EXTRACTION: Coordinates were extracted from clusters of significant gray matter difference between patients and controls. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors. DATA SYNTHESIS: Patients with anxiety disorders (including OCD) showed decreased bilateral gray matter volumes in the dorsomedial frontal/anterior cingulate gyri. Individuals with OCD had increased bilateral gray matter volumes (vs healthy controls and vs individuals with other anxiety disorders) in the lenticular/caudate nuclei, while patients with other anxiety disorders (mainly panic and posttraumatic stress disorders) had decreased gray matter volumes in the left lenticular nucleus. The findings remained largely unchanged in quartile and jackknife sensitivity analyses. Controlling for potential confounders such as age or antidepressant medication had little impact on the results. CONCLUSIONS: The meta-analysis consistently revealed common as well as distinct neural substrates in OCD and other anxiety disorders. These results have implications for the current debate surrounding the classification of OCD in the DSM-V.

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Method
Diagnostic biomarkers for obsessive-compulsive disorder: A reasonable quest or ignis fatuus?
Fullana, M. A., Abramovitch, A., Via, E., López-Sola, C., Goldberg, X., Reina, N., Fortea, L., Solanes, A., Buckley, M. J., Ramella-Cravaro, V., et al. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.08.008 · Cited by 44
Self-citation
Is deep brain stimulation a treatment option for anorexia nervosa?
Oudijn, M. S., Storosum, J. G., Nelis, E., & Denys, D. A. J. P. (2013) · BMC Psychiatry · doi:10.1186/1471-244x-13-277 · Cited by 45
Fear and safety learning in anxiety- and stress-related disorders: An updated meta-analysis
Kausche, F. M., Carsten, H. P., Sobania, K. M., & Riesel, A. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105983 · Cited by 48
A meta-analysis of voxel-based morphometric studies on migraine.
Hu, W., Guo, J., Chen, N., Guo, J., & He, L. (2015) · Europe PMC (PubMed Central) · Cited by 42
Abnormalities of localized connectivity in schizophrenia patients and their unaffected relatives: a meta-analysis of resting-state functional magnetic resonance imaging studies
Xiao, B., Wang, S., Liu, J., Meng, T., He, Y., & Luo, X. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s126678 · Cited by 41
Disentangling the role of gray matter volume and concentration in autism spectrum disorder: A meta-analytic investigation of 25 years of voxel-based morphometry research
Liloia, D., Zamfira, D. A., Tanaka, M., Manuello, J., Crocetta, A., Keller, R., Cozzolino, M., Duca, S., Cauda, F., & Costa, T. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105791 · Cited by 48
“Standard randomization tests, as outlined by Radua et al. (2010), were used to establish statistical significance.”
Structural Imaging in OCD
Veltman, D. J. (2021) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_209 · Cited by 41
Gray matter alterations in adolescent major depressive disorder and adolescent bipolar disorder
Long, X., Li, L., Wang, X., Cao, Y., Wu, B., Roberts, N., Gong, Q., Kemp, G. J., & Jia, Z. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.01.049 · Cited by 43
Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk
Modinos, G., Allen, P., Frascarelli, M., Tognin, S., Valmaggia, L., Xenaki, L., Keedwell, P. A., Broome, M. R., Valli, I., Woolley, J., et al. (2014) · Psychological Medicine · doi:10.1017/s0033291714000865 · Cited by 40
“Depressive and anxiety disorders have specific neuroanatomical, neurofunctional and neurochemical features (Radua et al. 2010; Sacher et al. 2012); therefore the high prevalence of these symptoms in UHR cohorts could potentially confound previous neurobiological findings in these subjects.”
Background
Support Vector Machine Classification of Obsessive-Compulsive Disorder Based on Whole-Brain Volumetry and Diffusion Tensor Imaging
Zhou, C., Cheng, Y., Ping, L., Xu, J., Shen, Z., Jiang, L., Shi, L., Yang, S., Lü, Y., & Xu, X. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00524 · Cited by 40
“Abnormal regional ACG volume has also been reported in previous VBM studies (54–57).”
Structural and functional brain abnormalities in misophonia
Eijsker, N., Schröder, A., Smit, D. J. A., van Wingen, G. A., & Denys, D. A. J. P. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.05.013 · Cited by 41
Altered EEG lagged coherence during rest in obsessive–compulsive disorder
Olbrich, S., Olbrich, H., Adamaszek, M., Jahn, I., Hegerl, U., & Stengler, K. (2013) · Clinical Neurophysiology · doi:10.1016/j.clinph.2013.05.031 · Cited by 38
“, 2005) and structural grey matter alterations (e.g. Radua and Mataix-Cols, 2009; Radua et al., 2010) the most compelling and consistent finding in OCD is of functional nature and describes alterations in mainly frontal cortical areas as reported by several studies that use different brain imaging modalities: Positron…”
A Functional Magnetic Resonance Imaging Study of a Large Clinical Cohort of Children With Tourette Syndrome
Debes, N. M., Hansen, A. E., Skov, L., & Larsson, H. B. W. (2011) · Journal of Child Neurology · doi:10.1177/0883073810387928 · Cited by 38
“The cingulate gyrus is known to be involved in obsessive-compulsive disorder.(63,64) Recent studies have shown that the superior temporal gyrus is involved in certain psychiatric disorders.”
Background
Regional brain volumes in body dysmorphic disorder compared to controls
Buchanan, B. G., Rossell, S. L., Maller, J. J., Toh, W. L., Brennan, S., & Castle, D. J. (2014) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867413520253 · Cited by 42
Reduced cortical thickness in non-medicated patients with obsessive-compulsive disorder
Nakamae, T., Narumoto, J., Sakai, Y., Nishida, S., Yamada, K., Kubota, M., Miyata, J., & Fukui, K. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.01.001 · Cited by 38
“Although there is increasing evidence of cortical grey matter volume reduction in patients with OCD (Radua et al., 2010; Rotge et al., 2009), the cause of such grey matter volume reduction, cortical thinning or other factors such as different gyrification has not been clarified.”
Background
Can Neuroimaging Provide Reliable Biomarkers for Obsessive-Compulsive Disorder? A Narrative Review
Frydman, I., Andrade, J. B. D. S., Vigne, P., & Fontenelle, L. F. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-016-0729-7 · Cited by 37
Is Migraine Associated to Brain Anatomical Alterations? New Data and Coordinate-Based Meta-analysis
Masson, R., Demarquay, G., David Meunier, A., Lévêque, Y., Hannoun, S., Bidet‐Caulet, A., & Caclin, A. (2021) · Brain Topography · doi:10.1007/s10548-021-00824-6 · Cited by 38
Neurocircuit models of obsessive-compulsive disorder: limitations and future directions for research
Shephard, E., Batistuzzo, M. C., Hoexter, M. Q., Stern, E. R., Zuccolo, P. F., Ogawa, C. Y., da Silva, R. D. M. F., Brunoni, A. R., Costa, D. L. D. C., Doretto, V. F., et al. (2021) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2020-1709 · Cited by 41
Cortico-basal ganglia circuits involved in different motivation disorders in non-human primates
Sgambato, V., Worbe, Y., Epinat‐Duclos, J., Féger, J., & Tremblay, L. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0911-9 · Cited by 42
Deep brain stimulation in the treatment of obsessive-compulsive disorder: current perspectives
Tastevin, M., Spatola, G., Régis, J. M., Lançon, C., & Richieri, R. M. (2019) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s178207 · Cited by 36
Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study
Tan, L., Fan, Q., You, C., Wang, J., Dong, Z., Wang, X., Chen, K., Xiao, Z., & Jiang, K. (2013) · Neuroscience Bulletin · doi:10.1007/s12264-013-1370-7 · Cited by 37
Obsessive compulsive disorder
Rapoport, J. L., & Shaw, P. (2015) · Wiley eBooks · doi:10.1002/9781118381953.ch61 · Cited by 36
Left inferior-parietal lobe activity in perspective tasks: identity statements
Arora, A., Weiss, B., Schurz, M., Aichhorn, M., Wieshofer, R. C., & Perner, J. (2015) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2015.00360 · Cited by 35
Neural dysfunction during temporal discounting in paediatric Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder
Norman, L. J., Carlisi, C. O., Christakou, A., Chantiluke, K. C., Murphy, C. M., Simmons, A., Giampietro, V., Brammer, M. J., Mataix‐Cols, D., & Rubia, K. (2017) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2017.09.008 · Cited by 35
“Previous research has established the importance of VMPFC/OFC and striatal regions in OCD (Menzies et al., 2008; Radua and Mataix-Cols, 2009; Radua et al., 2010; Saxena and Rauch, 2000), which are reliably activated during symptom provocation (Rotge et al., 2008), dysfunctional during cognitive and…”
InfluentialSelf-citation
Disturbance of approach‐avoidance behaviors in non‐human primates by stimulation of the limbic territories of basal ganglia and anterior insula
Saga, Y., Ruff, C. C., & Tremblay, L. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14201 · Cited by 37
“In humans, the central part of the vSTR is activated in learned active avoidance (Jensen et al., 2003; Delgado et al., 2009) and has shown structural anomalies in obsessive compulsive disorders and anxiety disorders (Radua et al., 2010).”
Background
Intrinsic brain abnormalities in drug-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study
Yang, X., Hu, X., Tang, W., Li, B., Yang, Y., Gong, Q., & Huang, X. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.11.080 · Cited by 36
Gray matter abnormalities and associated familial risk endophenotype in individuals with first-episode bipolar disorder: Evidence from whole-brain voxel-wise meta-analysis
Long, J., Qin, K., Wu, Y., Li, L., & Zhou, J. H. (2022) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2022.103179 · Cited by 35
Intolerance of uncertainty predicts increased striatal volume.
Kim, M. J., Shin, J., Taylor, J. M., Mattek, A. M., Chavez, S., & Whalen, P. J. (2017) · Emotion · doi:10.1037/emo0000331 · Cited by 36
“Reports of additional brain alterations observed in patient groups (Radua et al., 2010) lend themselves to the interesting speculation that the striatal alterations might be specific to IU, with the additional pathology necessary to observe the diagnosable condition.”
Background
A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
Li, D., Chang, X., Connolly, J. J., Tian, L., Liu, Y., Bhoj, E. J. K., Robinson, N., Abrams, D. J., Li, Y. R., Bradfield, J. P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01674-8 · Cited by 35
A Voxel-Wise Meta-Analysis of Gray Matter Abnormalities in Essential Tremor
Han, Q., Hou, Y., & Shang, H. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00495 · Cited by 35
Oral N-acetylcysteine in the treatment of obsessive-compulsive disorder: A systematic review of the clinical evidence
Couto, J. P., & Moreira, R. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.06.005 · Cited by 34
“, 2007)) and the medial OFC is hypoactivated (inversely correlated with symptom severity) (Radua et al., 2010).”
The effect of distress on the balance between goal-directed and habit networks in obsessive-compulsive disorder
van der Straten, A. L., van Leeuwen, W. A., Denys, D. A. J. P., van Marle, H. J. F., & van Wingen, G. A. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0744-7 · Cited by 33
White matter disruption in obsessive‐compulsive disorder revealed by meta‐analysis of tract‐based spatial statistics
Hu, X., Zhang, L., Bu, X., Li, H., Gao, Y., Lu, L., Tang, S., Wang, Y., Huang, X., & Gong, Q. (2020) · Depression and Anxiety · doi:10.1002/da.23008 · Cited by 34
Individual differences in common factors of emotional traits and executive functions predict functional connectivity of the amygdala
Rohr, C. S., Dreyer, F. R., Aderka, I. M., Margulies, D. S., Frisch, S., Villringer, A., & Okon‐Singer, H. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.06.049 · Cited by 34
“…caudate and the ACC has been observed in MDD (Gabbay et al., 2013), alongside increased connectivity between other areas in striatum and PFC. Abnormalities in the gray matter of these regions have also been linked to OCD and other anxiety disorders (Radua and Mataix-Cols, 2009; Radua et al., 2010).”
Background
How specific are inhibitory deficits to obsessive-compulsive disorder? A neurophysiological comparison with panic disorder
Thomas, S. J., Gonsalvez, C. J., & Johnstone, S. J. (2013) · Clinical Neurophysiology · doi:10.1016/j.clinph.2013.08.018 · Cited by 32
“While ERP studies have allowed the nuanced study of inhibition in OCD, as with brain imaging studies (Rauch et al. 1997; van den Heuvel et al. 2005; Radua et al. 2010), ERP studies comparing OCD with other disorders are extremely rare (Oades et al. 1996; Schall et al. 1997; Miyata et al. 1998),…”
Brain white matter integrity and association with age at onset in pediatric obsessive-compulsive disorder
Rosso, I. M., Olson, E. A., Britton, J. C., Stewart, S. E., Papadimitriou, G., Killgore, W. D. S., Makris, N., Wilhelm, S., Jenike, M. A., & Rauch, S. L. (2014) · Biology of Mood & Anxiety Disorders · doi:10.1186/s13587-014-0013-6 · Cited by 33
“, [10,11]).”
Dopamine and serotonin modulation of motor and non-motor functions of the non-human primate striato-pallidal circuits in normal and pathological states
Sgambato, V., & Tremblay, L. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1693-z · Cited by 37
Systematic Comparison of Brain Imaging Meta-Analyses of ToM with vPT
Arora, A., Schurz, M., & Perner, J. (2017) · BioMed Research International · doi:10.1155/2017/6875850 · Cited by 33
“31 for meta-analysis ([45, 46], http://www.”
Brain grey matter volume alterations associated with antidepressant response in major depressive disorder
Liu, J., Xu, X., Luo, Q., Luo, Y., Chen, Y., Lui, S., Wu, M. C., Zhu, H., Kemp, G. J., & Gong, Q. (2017) · Scientific Reports · doi:10.1038/s41598-017-10676-5 · Cited by 33
Brain Regional α-[11C]Methyl- L -Tryptophan Trapping in Medication-Free Patients With Obsessive-Compulsive Disorder
Berney, A., Leyton, M., Gravel, P., Sibon, I., Sookman, D., Rosa‐Neto, P., Dikšić, M., Nakai, A., Pinard, G., Todorov, C., et al. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.16 · Cited by 34
Deep TMS H7 Coil: Features, Applications & Future
Harmelech, T., Roth, Y., & Tendler, A. (2021) · Expert Review of Medical Devices · doi:10.1080/17434440.2021.2013803 · Cited by 34
Gray Matter Deficits in Panic Disorder
Lai, C. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31821a1045 · Cited by 32
Concordance of genetic variation that increases risk for Tourette Syndrome and that influences its underlying neurocircuitry
Mufford, M. S., Cheung, J. W., Jahanshad, N., van der Merwe, C., Ding, L., Groenewold, N. A., Koen, N., Chimusa, E. R., Dalvie, S., Ramesar, R., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0452-3 · Cited by 30
Comparative research on neural dysfunction in children with dyslexia under different writing systems: a meta-analysis study.
Li, Y.-Z., & Bi, H.-Y. (2022) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104650 · Cited by 30
Common and differential alterations of general emotion processing in obsessive-compulsive and social anxiety disorder
Weidt, S., Lutz, J., Rufer, M., Delsignore, A., Jakob, N. J., Herwig, U., & Bruehl, A. B. (2016) · Psychological Medicine · doi:10.1017/s0033291715002998 · Cited by 30
“In OCD, structural data consistently reported significantly smaller ACC volumes than in HCs (Rotge et al. 2009; Radua et al. 2010; de Wit et al. 2014), pointing towards a disease-related alteration in this area.”
Result
Why are psychiatric imaging methods clinically unreliable? Conclusions and practical guidelines for authors, editors and reviewers
Borgwardt, S., Raduà, J., Mechelli, A., & Fusar-Poli, P. (2012) · Behavioral and Brain Functions · doi:10.1186/1744-9081-8-46 · Cited by 37
“A recently developed meta-analytic method, Signed Differential Mapping [7,8], considers null findings as well and thus attenuates the disproportionate influence of single study data sets.”
Method
Ventral striatum supports Methylphenidate therapeutic effects on impulsive choices expressed in temporal discounting task
Martinez, E., Pasquereau, B., Drui, G., Saga, Y., Météreau, É., & Tremblay, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-57595-6 · Cited by 30

Authors: Radua, J., van den Heuvel, O. A., Surguladze, S., & Mataix-Cols, D.
Venue: Archives of General Psychiatry
Publisher: American Medical Association (AMA)
Published: 2010-07-01
Volume: 67
Issue: 7
Pages: 701-11
ISSN: 0003-990X (ISSN-L)
DOI: 10.1001/archgenpsychiatry.2010.70
OpenAlex: W2111531007
Cited by: 400
References: 104
Citations by year: 2026: 14 · 2025: 18 · 2024: 21 · 2023: 21 · 2022: 31 · 2021: 18 · 2020: 22 · 2019: 21 · 2018: 20 · 2017: 33 · 2016: 25 · 2015: 30 · 2014: 30 · 2013: 34 · 2012: 33
FWCI: 33.65
Type: journal article
Language: en
Open access: closed
Locations: Archives of General Psychiatry (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Topics: Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
Keywords: obsessive-compulsive disorder, anxiety disorders, gray matter volume, brain structural changes, dorsomedial frontal cortex, anterior cingulate cortex, caudate nucleus, lentiform nucleus, panic disorder, post-traumatic stress disorder, DSM-V, voxel-based morphometry
MeSH terms: Adult, Anxiety Disorders, Brain, Brain Mapping, Female, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Functional Laterality, Male, Obsessive-Compulsive Disorder, Online Systems, Psychiatric Status Rating Scales, Psychometrics, Diagnostic and Statistical Manual of Mental Disorders

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Meta-analytical Comparison of Voxel-Based Morphometry Studies in Obsessive-Compulsive Disorder vs Other Anxiety Disorders

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