TY - JOUR

T1 - Changes in negative symptoms are linked to white matter changes in superior longitudinal fasciculus in individuals at ultra-high risk for psychosis

AU - Kristensen, Tina D.

AU - Glenthøj, Louise B.

AU - Ragahava, Jayachandra M.

AU - Syeda, Warda

AU - Mandl, Rene C.W.

AU - Wenneberg, Christina

AU - Krakauer, Kristine

AU - Fagerlund, Birgitte

AU - Pantelis, Christos

AU - Glenthøj, Birte Y.

AU - Nordentoft, Merete

AU - Ebdrup, Bjørn H.

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Diffusion weighted imaging

KW - Longitudinal

KW - Negative symptoms

KW - Ultra-high risk of psychosis

KW - White matter

U2 - 10.1016/j.schres.2021.09.014

DO - 10.1016/j.schres.2021.09.014

M3 - Journal article

C2 - 34543833

AN - SCOPUS:85115014398

VL - 237

SP - 192

EP - 201

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

ER -