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JAMA Psychiatry. 2014 Apr;71(4):388-96. doi: 10.1001/jamapsychiatry.2013.4513.

A multicenter tractography study of deep white matter tracts in bipolar I disorder: psychotic features and interhemispheric disconnectivity.

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Pôle de Psychiatrie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor-Albert Chenevier, Créteil, France2Institut National de la Santé et de la Recherche Médicale (INSERM), U955, Institut Mondor de Recherche Biomédicale, Psychiatrie Géné
NeuroSpin, CEA Seclay, Gif-sur-Yvette, France.
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University, Heidelberg, Germany.
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Service de Psychiatrie, AP-HP, Hôpital Fernand Widal-Lariboisière, Paris, France.
NeuroSpin, CEA Seclay, Gif-sur-Yvette, France9Department of Electrical Engineering, Faculty of Engineering, University of Concepción, Concepción, Chile.
INSERM, Centre d'Investigation Clinique et Plateforme de Ressources Biologiques, Hôpitaux Henri Mondor, Créteil, France.



Tractography studies investigating white matter (WM) abnormalities in patients with bipolar disorder have yielded heterogeneous results owing to small sample sizes. The small size limits their generalizability, a critical issue for neuroimaging studies of biomarkers of bipolar I disorder (BPI).


To study WM abnormalities using whole-brain tractography in a large international multicenter sample of BPI patients and to compare these alterations between patients with or without a history of psychotic features during mood episodes.


A cross-sectional, multicenter, international, Q-ball imaging tractography study comparing 118 BPI patients and 86 healthy control individuals. In addition, among the patient group, we compared those with and without a history of psychotic features. University hospitals in France, Germany, and the United States contributed participants.


Participants underwent assessment using the Diagnostic Interview for Genetic Studies at the French sites or the Structured Clinical Interview for DSM-IV at the German and US sites. Diffusion-weighted magnetic resonance images were acquired using the same acquisition parameters and scanning hardware at each site. We reconstructed 22 known deep WM tracts using Q-ball imaging tractography and an automatized segmentation technique.


Generalized fractional anisotropy values along each reconstructed WM tract.


Compared with controls, BPI patients had significant reductions in mean generalized fractional anisotropy values along the body and the splenium of the corpus callosum, the left cingulum, and the anterior part of the left arcuate fasciculus when controlling for age, sex, and acquisition site (corrected for multiple testing). Patients with a history of psychotic features had a lower mean generalized fractional anisotropy value than those without along the body of the corpus callosum (corrected for multiple testing).


In this multicenter sample, BPI patients had reduced WM integrity in interhemispheric, limbic, and arcuate WM tracts. Interhemispheric pathways are more disrupted in patients with than in those without psychotic symptoms. Together these results highlight the existence of an anatomic disconnectivity in BPI and further underscore a role for interhemispheric disconnectivity in the pathophysiological features of psychosis in BPI.

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