Shape analysis of the cingulum, uncinate and arcuate fasciculi in patients with bipolar disorder

Shape analysis of the cingulum, uncinate and arcuate fasciculi in patients with bipolar disorder


J Psychiatry Neurosci 2017;42(1):27-36

Zhong Yi Sun, PhD; Josselin Houenou, MD, PhD; Delphine Duclap, MSc; Samuel Sarrazin, MD; Julia Linke, PhD; Claire Daban, PhD; Nora Hamdani, MD, PhD; Marc-Antoine d’Albis, MD; Philippe Le Corvoisier, MD, PhD; Pamela Guevara, PhD; Marine Delavest, MD; Frank Bellivier, MD, PhD; Jorge Almeida, MD, PhD; Amelia Versace, MD, PhD; Cyril Poupon, PhD; Marion Leboyer, MD, PhD; Mary Phillips, MD, PhD; Michèle Wessa, PhD; Jean-François Mangin, PhD


Background: Abnormal maturation of brain connectivity is supposed to underlie the dysfunctional emotion regulation in patients with bipolar disorder (BD). To test this hypothesis, white matter integrity is usually investigated using measures of water diffusivity provided by MRI. Here we consider a more intuitive aspect of the morphometry of the white matter tracts: the shape of the fibre bundles, which is associated with neurodevelopment. We analyzed the shape of 3 tracts involved in BD: the cingulum (CG), uncinate fasciculus (UF) and arcuate fasciculus (AF).

Methods: We analyzed diffusion MRI data in patients with BD and healthy controls. The fibre bundles were reconstructed using Q-ball–based tractography and automated segmentation. Using Isomap, a manifold learning method, the differences in the shape of the reconstructed bundles were visualized and quantified.

Results: We included 112 patients and 82 controls in our analysis. We found the left AF of patients to be further extended toward the temporal pole, forming a tighter hook than in controls. We found no significant difference in terms of shape for the left UF, the left CG or the 3 right fasciculi. However, in patients compared with controls, the ventrolateral branch of the left UF in the orbitofrontal region had a tendency to be larger, and the left CG of patients had a tendency to be smaller in the frontal lobe and larger in the parietal lobe.

Limitations: This was a cross-sectional study.

Conclusion: Our results suggest neurodevelopmental abnormalities in the left AF in patients with BD. The statistical tendencies observed for the left UF and left CG deserve further study.

Submitted Sept. 2, 2015; Revised Jan. 1, 2016; Revised Jan. 29, 2016; Revised Feb. 2, 2016; Accepted Feb. 3, 2016; Early-released June 28, 2016

Acknowledgements: The authors thank all those who participated in this study and the personnel of participating centres for their help with data collection.

Affiliations: From the UNATI, Neurospin, I2BM, CEA Saclay, Gif-Sur-Yvette, France (Sun, Mangin); the UNIACT, Psychiatry Team, Neurospin, I2BM, CEA Saclay, Gif-Sur-Yvette, France (Houenou, Sarrazin); INSERM, U955, IMRB, Equipe 15 Psychiatrie Translationnelle, Créteil F-94000, France (Houenou, Sarrazin, Hamdani, d’Albis, Leboyer); the Fondation Fondamental, Créteil F-94010, France (Houenou, Sarrazin, Hamdani, d’Albis, Delavest, Bellivier, Leboyer); the AP-HP, Hôpitaux Universitaires Mondor, Pôle de Psychiatrie, DHU PePsy, Université Paris Est, Créteil F-94000, France (Sarrazin, Daban, Hamdani, d’Albis, Leboyer); the UNIRS, Neurospin, I2BM, CEA Saclay, Gif-Sur-Yvette, France (Duclap, Poupon); the Department of Clinical Psychology and Neuropsychology, Johannes Gutenberg University, Mainz, Germany (Linke, Wessa); INSERM, Centre d’Investigation Clinique 1430 and APHP, GH Henri Mondor, Créteil F-94000, France (Le Corvoisier); the University of Concepción, Concepción, Chile (Guevara); the AP-HP, Groupe Saint-Louis, Lariboisière-Fernand Widal, Pôle Neurosciences, Paris, France (Delavest, Bellivier); the Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medecine, Pittsburgh, PA, USA (Almeida, Versace, Phillips); the Faculté de médecine, Universite Paris Est, Créteil, France (Leboyer); and the CATI Multicenter Neuroimaging Platform, France (Sun, Poupon, Mangin).

Funding: This work was supported by public funding from the Alliance pour les Sciences de la Vie et de la Santé (ITMO Neurosciences), the Agence Nationale pour la Recherche (ANR MNP VIP 2008 and ANR-11-IDEX-0004 Labex BioPsy), the Fondation pour la Recherche Médicale (Appel d’offres analyse bioinformatique pour la recherche en biologie 2014), the Deutsche Forschungsgemeinschaft (SFB636/C6 and We3638/3-1), and the NIMH R01 MH076971. S.Sarrazin is supported by a grant from the Agence Régionale de Santé Ile-de-France. The funders did not participate in the design and conduct of the study, in the collection, analysis or interpretation of the data; or in the preparation, review or approval of the manuscript.

Competing interests: S. Sarrazin declares travel expenses from Otsuka outside the submitted work. M. Phillips is a consultant with Roche.

Contributors: J. Houenou, D. Duclap, P. Le Corvoisier, M. Delavest, A. Versace, C. Poupon and M. Leboyer designed the study. J. Houenou, S. Sarrazin, J. Linke, C. Daban, N. Hamdani, M.-A. d’Albis, P. Le Corvoisier, F. Bellivier, J. Almeida, A. Versace, M. Phillips, M. Wessa and J.-F. Mangin acquired the data, which Z. Sun, J. Houenou, S. Sarrazin, P. Guevara, C. Poupon, M. Phillips and J.-F. Mangin analyzed. Z. Sun, J. Houenou and J.-F. Mangin wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150291

Correspondence to: J. Houenou, INSERM U955, IMRB, Equipe 15, Psychiatrie Translationnelle, 40 rue de Mesly, 94000 Créteil, France;