White matter maturation during 12 months in individuals at ultra‐high‐risk for psychosis

Acta Psychiatrica Scandinavica, Wiley, ISSN 0001-690X

Volume 137, 1, 2018

DOI:10.1111/acps.12835, Dimensions: pub.1092708704, PMID: 29143980,


Krakauer, K. (1) (2) (3)
Nordentoft, M. (1) (2)
Raghava, J. M. (1) (3) (4)
Nordholm, D. (1) (2)
Randers, L. (1) (2)
Ebdrup, B. H. (1) (4)
Rostrup, E. (3) (5)



  1. (1) Copenhagen University Hospital Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS Glostrup Denmark
  2. (2) Copenhagen University Hospital Mental Health Centre Copenhagen Hellerup Denmark
  3. (3) Copenhagen University Hospital Rigshospitalet Functional Imaging Unit, FIUNIT Glostrup Denmark
  4. (4) Copenhagen University Hospital Centre for Neuropsychiatric Schizophrenia Research, CNSR Glostrup Denmark
  5. (5) Rigshospitalet, grid.475435.4, Capital Region






OBJECTIVE: The neurodevelopmental hypothesis of psychosis suggests that disrupted white matter (WM) maturation underlies disease onset. In this longitudinal study, we investigated WM connectivity and compared WM changes between individuals at ultra-high-risk for psychosis (UHR) and healthy controls (HCs). METHOD: Thirty UHR individuals and 23 HCs underwent MR diffusion tensor imaging before and after 12 months of non-manualized standard care. Positive and negative symptoms and level of functioning were assessed. Tract-based spatial statistics were employed. RESULTS: During 12 months, none of the UHR individuals transitioned to psychosis. Both UHR individuals and HCs increased significantly in fractional anisotropy (FA). UHR individuals showed significant FA increases predominantly in the left superior longitudinal fasciculus (SLF) (P = 0.01), and HCs showed significant FA increases in the left uncinate fasciculus (P = 0.03). Within UHR individuals, a significant positive correlation between FA change and age was observed predominantly in the left SLF (P = 0.02). Within HCs, no significant correlation between FA change and age was observed. No significant correlations between baseline FA and clinical outcomes were observed; however, FA changes were significantly positively correlated to changes in negative symptoms (P = 0.04). CONCLUSION: As normal brain maturation occurs in a posterior to frontal direction, our findings could suggest disturbed WM maturation in UHR individuals.

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