Changes in negative symptoms are linked to white matter changes in superior longitudinal fasciculus in individuals at ultra-high risk for psychosis

Tina D Kristensen; Louise B Glenthøj; Jayachandra M Raghava; Warda Syeda; Rene C W Mandl; Christina Wenneberg; Kristine Krakauer; Birgitte Fagerlund; Christos Pantelis; Birte Y Glenthøj; Merete Nordentoft; Bjørn H Ebdrup

doi:10.1016/j.schres.2021.09.014

Changes in negative symptoms are linked to white matter changes in superior longitudinal fasciculus in individuals at ultra-high risk for psychosis

Schizophr Res. 2021 Nov:237:192-201. doi: 10.1016/j.schres.2021.09.014. Epub 2021 Sep 17.

Affiliations

¹ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Copenhagen Research Centre for Mental Health (CORE), Copenhagen University Hospital, Denmark. Electronic address: tina.dam.kristensen@regionh.dk.
² Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Copenhagen Research Centre for Mental Health (CORE), Copenhagen University Hospital, Denmark.
³ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, University of Copenhagen, Glostrup, Denmark.
⁴ Melbourne Neuropsychiatry Center, Department of Psychiatry, The University of Melbourne, and Melbourne Health, Carlton South, Victoria, Australia.
⁵ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; University Medical Center Utrecht Brain Center, Utrecht, the Netherlands.
⁶ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Department of Psychology, Faculty of Social Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Melbourne Neuropsychiatry Center, Department of Psychiatry, The University of Melbourne, and Melbourne Health, Carlton South, Victoria, Australia.
⁸ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Copenhagen Research Centre for Mental Health (CORE), Copenhagen University Hospital, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, and Center for Neuropsychiatric Schizophrenia Research, CNSR, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark; Melbourne Neuropsychiatry Center, Department of Psychiatry, The University of Melbourne, and Melbourne Health, Carlton South, Victoria, Australia; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

PMID: 34543833
DOI: 10.1016/j.schres.2021.09.014

Abstract

Aim: Growing evidence suggests that subtle white matter (WM) alterations are associated with psychopathology in individuals at ultra-high risk for psychosis (UHR). However, the longitudinal relationship between symptom progression and WM changes over time remains under-explored. Here, we examine associations between changes in clinical symptoms and changes in WM over six months in a large UHR-cohort.

Methods: 110 UHR-individuals and 59 healthy controls underwent diffusion weighted imaging at baseline and after six months. Group × time effects on fractional anisotropy (FA) were tested globally and in four predefined regions of interest (ROIs) bilaterally using linear modelling with repeated measures. Correlations between the changes in clinical symptoms and FA changes in the ROIs were examined with Pearson's correlation. A partial least squares correlation-technique (PLS-C) explored multivariate associations between patterns of changes in psychopathology, regional FA and additional WM indices.

Results: At baseline, UHR-individuals displayed significantly lower FA globally (p = 0.018; F = 12.274), in right superior longitudinal fasciculus (p = 0.02; Adj R² = 0.07) and in left uncinate fasciculus (p = 0.048; Adj R² = 0.058) compared to controls (corrected). We identified a group × time interaction in global FA and right superior longitudinal fasciculus, but the finding did not survive multiple comparisons. However, an increase of negative symptoms in UHR-individuals correlated with FA increase in right superior longitudinal fasciculus (p = 0.048, corrected, r = 0.357), and this finding was supported by the multivariate PLS-C.

Conclusion: We found a positive correlation with a moderate effect between change in negative symptoms and FA change over 6 months in right superior longitudinal fasciculus. This link appeared mainly to reflect a subgroup of UHR-individuals, which already at baseline presented as vulnerable.

Keywords: Diffusion weighted imaging; Longitudinal; Negative symptoms; Ultra-high risk of psychosis; White matter.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anisotropy
Diffusion Magnetic Resonance Imaging / methods
Humans
Nerve Net / pathology
Psychotic Disorders* / diagnostic imaging
Psychotic Disorders* / pathology
White Matter* / diagnostic imaging
White Matter* / pathology