White Matter Integrity and Verbal Memory After a First Episode of Psychosis: A Longitudinal Study

Poster No:


Submission Type:

Abstract Submission 


Joseph Ghanem1, Jana Totzek1, Charlie Henri-Bellemare1, Ethan Draper2, Delphine Raucher-Chéné2, Gregory Kiar3, Raihaan Patel4, Mallar Chakravarty5, Jai Shah1, Ridha Joober1, Ashok Malla1, Martin Lepage1, Katie Lavigne1


1McGill University, Montreal, Quebec, 2McGill University, Montreal, QC, 3Child Mind Institute, Montreal, Quebec, 4Department of Psychiatry, University of Oxford, Oxford, Oxfordshire, 5Brain Imaging Centre, Douglas Research Centre, Montreal, Quebec

First Author:

Joseph Ghanem  
McGill University
Montreal, Quebec


Jana Totzek, M.Sc.  
McGill University
Montreal, Quebec
Charlie Henri-Bellemare, MSc  
McGill University
Montreal, Quebec
Ethan Draper  
McGill University
Montreal, QC
Delphine Raucher-Chéné  
McGill University
Montreal, QC
Gregory Kiar  
Child Mind Institute
Montreal, Quebec
Raihaan Patel  
Department of Psychiatry, University of Oxford
Oxford, Oxfordshire
Mallar Chakravarty, PhD  
Brain Imaging Centre, Douglas Research Centre
Montreal, Quebec
Jai Shah  
McGill University
Montreal, Quebec
Ridha Joober  
McGill University
Montreal, Quebec
Ashok Malla  
McGill University
Montreal, Quebec
Martin Lepage  
McGill University
Montreal, Quebec
Katie Lavigne, Ph.D.  
McGill University
Montreal, Quebec


Studies of white matter differences in psychotic disorders have reported lower fractional anisotropy (FA) in individuals with schizophrenia relative to controls(1, 2), but the evidence in First Episode Psychosis (FEP) samples remains controversial. Many cross-sectional FEP studies observed no group differences in FA(3, 4), whereas the few available longitudinal studies observed a reduction in FA in certain regions relative to controls (5, 6). Importantly, these studies were limited by short follow-up periods (6 and 12 weeks, respectively), and did not investigate the relationship between changes in FA and verbal memory, the cognitive domain most impaired in FEP. However, some cross-sectional examinations found positive correlations between verbal memory and FA in the anterior limb of the internal capsule (7) and the cingulum (8). In the present study, we aimed to examine, over 15 months, longitudinal changes in FA and their association with changes in verbal memory in a large sample of individuals with a FEP.


Eighty Individuals with a FEP aged 18-35 were recruited from the 2-year Prevention and Early Intervention for Psychosis Program (PEPP) located in the catchment area of Southwest Montreal. Following clinical stabilization, they were scanned and assessed within the first 3 months of admission to PEPP and at months 6, 12, and 18. Fifty-five healthy controls were similarly scanned four times over 18 months. Verbal memory was assessed using the logical memory subtest of the Wechsler Memory Scale shortly prior to the scan at every timepoint. Two successive whole-brain diffusion-weighted images were acquired using a single-shot EPI sequence parallel to the anterior-posterior commissural plane. Preprocessing of diffusion images was performed using the FMRIB software library tools (9). Subsequent diffusion image processing was performed using MRtrix 3.0 (10). Tract-based spatial statistics were generated using the procedure outlined by the ENIGMA consortium-DTI group where each subject's FA map was skeletonized and used to extract the average FA per white matter region using the JHU-White matter parcellation. Group differences in FA and verbal memory over time were examined using linear mixed-effects models with age, sex, and years of education as covariates. Tests were corrected for multiple comparisons and considered significant at a 5% false discovery rate.


At baseline, the FEP group was 63% male and 37% female, and the healthy control group was 66% male and 34% female. Individuals with a FEP had fewer years of education (t(133)=3.90, p<.001), and lower IQ relative to controls (t(133)= 3.66, p<.001).

There was a significant main effect of time on FA in the left cingulum (Pcorrected= .022), the right internal capsule (Pcorrected= .024), the right posterior limb of the internal capsule (Pcorrected= .009), and the right inferior fronto-occipital fasciculus (Pcorrected=0.041). However, there was no significant group difference between FEP and controls in FA, and no significant interaction of group and time. Similarly, there was no significant main effect of verbal memory on FA, and no interaction between group, time, and verbal memory on FA.


In this longitudinal study, we observed a general change in FA over time in some white matter regions. FEP and controls did not significantly differ in FA, and there was no relationship between change in FA and in verbal memory over time. Our results are consistent with previous work that found no differences in FA between FEP and controls early in the course of illness. It is possible that early exposure to antipsychotic medication may have attenuated any observable differences, or that group differences are small in the early stages of psychosis but progressively evolve over longer time periods. Future studies should follow individuals with a FEP for longer timeframes and integrate different measures of diffusion to capture a more comprehensive picture of white matter changes over time.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Modeling and Analysis Methods:

Diffusion MRI Modeling and Analysis 2


Psychiatric Disorders
White Matter

1|2Indicates the priority used for review

Provide references using author date format

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