J Psychiatry Neurosci 2014;39(6):417-27
Sean N. Hatton, BMedSci(Hons); Jim Lagopoulos, PhD; Daniel F. Hermens, PhD; Ian B. Hickie, MD; Elizabeth Scott, MBBS; Maxwell R. Bennett, DSc
Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Camperdown, NSW, Australia
Background: While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis.
Methods: We obtained MRI scans from young people with psychosis and healthy controls. Eighteen major white matter tracts were reconstructed to determine group differences in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) and then were subsequently correlated with symptomatology and neurocognitive performance.
Results: Our study included 42 young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25 yr). Compared with the control group, the psychosis group had reduced FA and AD in the left inferior longitudinal fasciculus (ILF) and forceps major indicative of axonal disorganization, reduction and/or loss. These changes were associated with worse overall psychiatric symptom severity, increases in positive and negative symptoms, and worse current levels of depression. The psychosis group also showed FA reductions in the left superior longitudinal fasciculus that were associated with impaired neurocognitive performance in attention and semantic fluency.
Limitations: Our analysis grouped 4 subcategories of psychosis together, and a larger follow-up study comparing affective and nonaffective psychoses is warranted.
Conclusion: Our findings suggest that impaired axonal coherence in the left ILF and forceps major underpin psychiatric symptoms in young people in the early stages of psychosis.
Submitted Dec. 11, 2013; Revised Feb. 28, Apr. 9, 2014; Accepted Apr. 14, 2014; Early-released Aug. 12, 2014.
Acknowledgements: The authors thank Rico Sze Chun Lee and Django White for their assistance with data collection. They also thank individuals that participated in this study.
Competing interests: S.N. Hatton, D.F. Hermens and I.B. Hickie are supported by a National Health and Medical Research Council Program Grant (566529), a Centres of Clinical Research Excellence Grant (264611), an Australia Fellowship (464914) and a Clinical Research Fellowship (402864). S.N. Hatton and D.F. Hermens have received personal fees for educational seminars from Janssen-Cilag and Eli Lilly, and S.N. Hatton and I.B. Hickie have received grants from Servier and Pfizer for investigator-led trials. No other competing interests declared.
Contributors: All authors designed the study. S.N. Hatton, J. Lagopoulos, D.F. Hermens, E. Scott and M.R. Bennett acquired the data, which S. Hatton, J. Lagopoulos, D.F. Hermens, I.B. Hickie and M.R. Bennett analyzed. S.N. Hatton, J. Lagopoulos, D.F. Hermens, I.B. Hickie and M.R. Bennett wrote the article, which all authors reviewed and approved for publication.
Correspondence to: S.N. Hatton, Brain and Mind Research Institute, University of Sydney, 94 Mallet St., Camperdown, NSW, 2050, Australia; firstname.lastname@example.org