RT Journal Article
SR Electronic
T1 Resting-state functional connectivity and psychopathology in Klinefelter syndrome (47, XXY)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.15.422868
DO 10.1101/2020.12.15.422868
A1 Ethan T. Whitman
A1 Siyuan Liu
A1 Erin Torres
A1 Allysa Warling
A1 Kathleen Wilson
A1 Ajay Nadig
A1 Cassidy McDermott
A1 Liv S. Clasen
A1 Jonathan D. Blumenthal
A1 François M. Lalonde
A1 Stephen J. Gotts
A1 Alex Martin
A1 Armin Raznahan
YR 2020
UL http://biorxiv.org/content/early/2020/12/16/2020.12.15.422868.abstract
AB Klinefelter syndrome (47, XXY; Henceforth: XXY syndrome) is a high impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first neuroimaging study to map resting-state functional connectivity (rsFC) changes in XXY syndrome and ask how these might relate to brain anatomy and psychopathology. We collected resting state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males. We implemented a brain-wide screen to identify regions with altered global rsFC in XXY vs. XY males, and then used seed-based analysis to decompose these alterations. We further compared rsFC changes with regional changes in brain volume from voxel-based morphometry and tested for correlations between rsFC and symptom variation within XXY syndrome. We found that XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC), associated with overconnectivity with diverse rsFC networks. Regional rsFC changes were partly coupled to regional volumetric changes in XXY syndrome. Within the precuneus, variation in DLPFC rsFC within XXY syndrome was correlated with the severity of psychopathology in XXY individuals. Our findings provide the first view of altered functional brain connectivity in XXY syndrome and delineate links between these alterations and those relating to both brain anatomy and psychopathology. Taken together, these insights advance biological understanding of XXY syndrome as a disorder in its own right, and as a model of genetic risk for psychopathology more broadly.Competing Interest StatementThe authors have declared no competing interest.