White matter integrity and peripheral inflammatory markers in obsessive-compulsive disorder

Poster No:

2198 

Submission Type:

Abstract Submission 

Authors:

Nelson Descalço1, Ana Maia2, Nuno Loução2, Jaime Caballero-Insaurriaga3, João Valente Duarte2, Catarina Fonseca4, José Oliveira2, J. Bernardo Barahona-Corrêa2, Albino J. Oliveira-Maia2

Institutions:

1Champalimaud Foundation, Lisbon, Lisbon, 2Champalimaud Research and Clinical Centre, Champalimaud Foundation, Lisbon, Portugal, 3Champalimaud Research and Clinical Centre, Champalimaud Foundation, Lisbon, Lisbon, 4NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisbon, Portugal

First Author:

Nelson Descalço, MD  
Champalimaud Foundation
Lisbon, Lisbon

Co-Author(s):

Ana Maia  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
Nuno Loução  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
Jaime Caballero-Insaurriaga  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Lisbon
João Valente Duarte  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
Catarina Fonseca  
NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa
Lisbon, Portugal
José Oliveira  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
J. Bernardo Barahona-Corrêa  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
Albino J. Oliveira-Maia  
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal

Introduction:

Diffusion-weighted imaging (DWI) is widely used to study white matter (WM) structural integrity in neuropsychiatric disorders. Despite the increasing number of DWI models and metrics, the most studied index of WM integrity continues to be fractional anisotropy (FA), which can be used as a proxy for WM fiber injury. Obsessive-compulsive disorder (OCD), a common and chronic neuropsychiatric disorder, has been extensively studied using DWI techniques. Indeed, DWI studies report widespread WM abnormalities mainly in the corpus callosum and the left inferior frontal gyrus. However, the pathophysiology of such WM structural changes in OCD is not clearly understood. In other conditions, abnormal DWI-derived indexes of WM integrity have been associated with increased concentration of inflammatory markers in peripheral blood, such as C Reactive Protein (CRP) and several cytokines. In OCD, inflammation may have a relevant role, given the well-known contributions of childhood adversity and early-life infections in the etiology and neurobiology of OCD. Here we tested if changes in WM integrity, as assessed with DWI, are associated with peripheral inflammatory markers in patients with OCD. Specifically, we aimed to 1) identify WM abnormalities in patients with OCD compared to healthy controls; and 2) test if these WM abnormalities are associated with CRP levels in peripheral blood.

Methods:

Patients with OCD (n=70) and age- and sex-matched healthy controls (n=69) were assessed for sociodemographic and clinical variables. Participants underwent multishell DWI acquisition in a 3.0Tesla scanner. Diffusion data were preprocessed, and scalar maps of FA were estimated using DSI Studio. Additionally, a peripheral blood sample was collected from all participants, and serum was processed and stored. For aim 1, we used tract-based spatial statistics (TBSS) from FMRIB Software Library to map between-groups FA differences in a group-derived skeleton. Voxel-wise significant differences were assessed with permutation-based (5000 permutations) two-sample t-test (one-tailed and α<0.05) with threshold-free cluster enhancement (TFCE), and voxels were labelled using the JHU ICBM-DTI-81 WM atlas. Mean FA values were extracted, for each participant, from clusters of voxels with significant group-differences and used for correlation analysis with clinical variables in patients with OCD, corrected for multiple comparisons. For aim 2, high sensitivity CRP (hsCRP) concentration was determined in serum using enzyme-linked immunosorbent assay. Mean FA values, as obtained in the previous aim, were used for correlation analysis with hsCRP. All statistical analyses were adjusted for age and sex.

Results:

Patients with OCD had significantly lower FA in the corpus callosum, anterior corona radiata and superior corona radiata. Also, among patients, mean FA values were not significantly correlated with OCD symptom severity or depression symptoms.
While patients with OCD and healthy controls did not differ in peripheral blood hsCRP concentration (z=0.2; p=0.9), mean FA values correlated negatively with hsCRP in patients with OCD (ß-coefficient=-0.3; p=0.006) but not in healthy controls (ß-coefficient=-0.1; p=0.6).

Conclusions:

Our results confirm that patients with OCD have significant WM abnormalities compared to healthy controls, and that such changes do not correlate with disease-related clinical variables. Although we have found no differences regarding hsCRP between the two groups, this marker of immune function was negatively correlated with FA in those brain regions that showed WM abnormalities in patients. This raises the hypothesis that patients with OCD may have an innate or acquired vulnerability to the effects of peripheral inflammation in the WM structure.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2

Modeling and Analysis Methods:

Diffusion MRI Modeling and Analysis

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

White Matter Anatomy, Fiber Pathways and Connectivity 1

Novel Imaging Acquisition Methods:

Diffusion MRI

Keywords:

MRI
Obessive Compulsive Disorder
Psychiatric Disorders
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

1|2Indicates the priority used for review

Provide references using author date format

Yeh, Fang-Cheng, et al. "Deterministic diffusion fiber tracking improved by quantitative anisotropy." (2013): e80713. PLoS ONE 8(11): e80713. doi:10.1371/journal.pone.0080713