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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftSchizophrenia Research
Vol/bind237
Sider (fra-til)192-201
Antal sider10
ISSN0920-9964
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The study has been funded through The Danish Council for Independent Research ( DFF-4004-00314 ); TrygFonden (ID 108119 ); the Mental Health Services in the Capital Region of Denmark; the Research Fund of the Capital Region of Denmark ; the Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS ( R155-2013-16337 ). C. Pantelis was supported by an Australian NHMRC Senior Principal Research Fellowship (ID: 1105825 ) and by a grant from the Lundbeck Foundation (ID: R246-2016-3237 ).

Funding Information:
Dr. Glenthøj is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. Her group has also received a research grant from Lundbeck A/S for another independent investigator-initiated study. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose.

Publisher Copyright:
© 2021 The Authors

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