A multicenter tractography study of deep white matter tracts in bipolar I disorder

Sarrazin, Samuel, Poupon, Cyril, Linke, Julia, Wessa, Michèle, Phillips, Mary, Delavest, Marine, Versace, Amelia, Almeida, Jorge, Guevara, Pamela, Duclap, Delphine, Duchesnay, Edouard, Mangin, Jean-François, Le Dudal, Katia, Daban, Claire, Hamdani, Nora, D'Albis, Marc-Antoine, Leboyer, Marion and Houenou, Josselin 2014. A multicenter tractography study of deep white matter tracts in bipolar I disorder. JAMA Psychiatry 71 (4) , pp. 388-396. 10.1001/jamapsychiatry.2013.4513

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Abstract

Importance 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). Objectives 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. Design, Setting, and Participants 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. Interventions 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. Main Outcomes and Measures Generalized fractional anisotropy values along each reconstructed WM tract. Results 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). Conclusions and Relevance 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. White matter (WM) abnormalities have been widely detected in the pathophysiological features of bipolar disorder (BD),1 mainly using diffusion tensor imaging (DTI) studies.2 Diffusion tensor imaging uses the properties of water molecule motion to provide insights into the microscopic structure of brain tissues with fractional anisotropy (FA), a quantitative index that reflects the integrity and coherence of WM.3 Few studies have applied tractography methods to BD despite several advantages. Indeed, the virtual reconstruction of entire WM tracts provides comprehensive anatomic information and allows for anatomically driven hypothesis testing for changes in FA. Despite discrepancies,4,5 most studies in BD reported decreased FA values along tracts linking regions involved in emotion processing, including the uncinate fasciculus,6- 9 the anterior thalamic radiations,8,9 and the cingulum.6,10 Such impairments are thought to underpin the emotional dysregulation observed in the patients11 and are further considered to be a relevant candidate biomarker for BD.1 Tractography studies in BD have included relatively small samples (≤40 patients with BD9), thus limiting the generalizability of their conclusions. Multicenter imaging studies including larger samples can help to address those issues.12 Furthermore, a relatively larger sample allows for the disentangling of a heterogeneous sample of patients by focusing on a clinical feature of interest. This possibility is worth exploiting in a complex clinical condition such as BD. At least 50% of patients with BD experience psychotic features during phases of acute illness.13 Despite substantial overlap in psychotic features and genetic susceptibility between BD and schizophrenia, growing evidence from clinical14 and genetic15 studies support the view that BD with psychotic features can be seen as a homogeneous subtype of BD. However, despite the high prevalence of BD with psychotic features, the relation of this subtype to different WM alterations compared with nonpsychotic BD remains poorly explored. Thus, we designed a large, multicenter, whole-brain tractography study in patients with bipolar I disease (BPI). As our main objective, we probed microstructural properties of 22 major deep WM tracts covering the whole brain in a large sample of BPI patients and controls using Q-ball imaging (QBI) tractography. Our secondary objective was to investigate whether these disruptions were different in subsamples of BPI patients with or without a history of psychotic features.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Medical Association
ISSN:	2168-622X
Last Modified:	14 Mar 2019 12:48
URI:	https://orca.cardiff.ac.uk/id/eprint/75182

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