J Psychiatry Neurosci 2016;41(2):115-123
Marta Subirà, MD; Marta Cano, MSc; Stella J. de Wit, MD; Pino Alonso, MD, PhD; Narcís Cardoner, MD, PhD; Marcelo Q. Hoexter, MD, PhD; Jun Soo Kwon, MD, PhD; Takashi Nakamae, MD, PhD; Christine Lochner, PhD; João R. Sato, PhD; Wi Hoon Jung, PhD; Jin Narumoto, MD, PhD; Dan J. Stein, MD, PhD; Jesus Pujol, MD, PhD; David Mataix-Cols, PhD; Dick J. Veltman, MD, PhD; OCD Brain Imaging Consortium; José M. Menchón, MD, PhD; Odile A. van den Heuvel, MD, PhD; Carles Soriano-Mas, PhD
Background: Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive–compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored.
Methods: We performed a mega-analysis pooling structural MRI scans from the Obsessive–compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software.
Results: Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex.
Limitations: This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres.
Conclusion: Our results provide evidence for structural network–level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders.
Submitted Jan. 16, 2015; Revised May 16, 2015; Accepted June 26, 2015; Early-released Oct. 20, 2015
Acknowledgements: This study was supported by the Carlos III Health Institute (PI09/01331, PI12/01306, PI13/00918, PI14/00413, CP10/00604, PI13/01958, and CIBER-CB06/03/0034); FEDER funds (“A way to build Europe”); the Agency for Administration of University and Research (AGAUR, Barcelona; 2014SGR1672); a “Miguel Servet” contract from the Carlos III Health Institute (CP10/00604) to C. Soriano-Mas; a grant from the Bellvitge Biomedical Research Institute (IDIBELL) (06/IDB001) to M. Subirà; a grant from the Spanish Ministry for Education, Culture and Sport to M. Cano (FPU13/02141); the Dutch Organization for Scientific Research (NWO) (grants 912-02-050, 907-00- 012, 940-37-018, and 916.86.038); grants from the Foundation for the Support of Research in the State of São Paulo (FAPESP) to M. Hoexter (2005/04206-6) and J. Sato (2013/10498-6); a National Research Foundation of Korea grant funded by the Korean government (Ministry of Education, Science, and Technology, 2012-0005150); a Ministry of Education, Culture, Sports, Science, and Technology (Japan) Grants-in-Aid for Young Scientists to J. Narumoto (23591724) and to T. Nakamae (24791223); the Medical Research Council of South Africa; Wellcome Trust project (grant 064846) and South London and Maudsley Trust.
Affiliations: From the Psychiatry Department, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (Subirà, Cano, Alonso, Cardoner, Menchón, Soriano-Mas); the Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain (Subirà, Alonso, Pujol, Menchón, Soriano-Mas); the Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain (Subirà, Cano, Alonso, Menchón); the Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands (De Wit, Veltman, Van den Heuvel, Schweren); the Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, the Netherlands (De Wit, Veltman, Van den Heuvel, Remijnse); the Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil (Hoexter, Busatto, Miguel); the Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea (Kwon, Jang, Kim, Shin); the Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Korea (Kwon, Jung); the Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan (Nakamae, Narumoto, Fukui, Nishida, Sakai); the MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa (Lochner); Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil (Sato); the Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa (Stein, Fouche); the MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain (Pujol); Mental Health Department, Corporació Sanitària Parc Taulí, Sabadell, Spain (Cardoner); Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain (Cardoner); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM G21, Barcelona, Spain (Pujol); the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Mataix-Cols); the Department of Psychobiology and Methodology in Health Sciences, Autonomous University of Barcelona, Barcelona, Spain (Soriano-Mas); the Altrecht Academic Anxiety Center, Utrecht, the Netherlands (Cath); Department of Psychiatry, Academic Medical Center, Amsterdam, the Netherlands (Denys); the Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburg School of Medicine, Pittsburgh, USA (Phillips); and the Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan (Yamada).
Competing interests: D. Stein declares personal fees from Lundbeck, Novartis, AMBRF, Sun and Cipla outside the submitted work. O. van den Heuvel has received speaker fees from Lundbeck. No other competing interests declared.
Contributors: M. Subirà, S. de Wit, P. Alonso, N. Cardoner, D. Stein, J. Menchón, O. van den Heuvel and C. Soriano-Mas designed the study. M. Subirà, P. Alonso, M. Hoexter, J.-S. Kwon, T. Nakamae, J. Sato, W.-H. Jung, J. Narumoto, D. Stein, J. Pujol, D. Mataix-Cols, D. Veltman, J. Menchón, O. van den Heuvel and C. Soriano-Mas acquired the data, which M. Subirà, M. Cano, S. de Wit, N. Cardoner, C. Lochner, D. Veltman, O. van den Heuvel and C. Soriano-Mas analyzed. M. Subirà, M. Cano and C. Soriano-Mas wrote the article, which all authors reviewed and approved for publication.
OCD Brain Imaging Consortium: Geraldo F. Busatto, Danielle C. Cath, Damiaan Denys, Kenji Fukui, Jean-Paul Fouche, Joon Hwan Jang, Sung Nyun Kim, Euripides C. Miguel, Seiji Nishida, Mary L. Phillips, Peter L. Remijnse, Yuki Sakai, Lizanne Schweren, Na Young Shin, Kei Yamada.
Correspondence to: C. Soriano-Mas, Bellvitge Biomedical Research Institute-IDIBELL, Psychiatry Department, Bellvitge University Hospital, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain; email@example.com