Characterising grey-white matter relationships in recent-onset psychosis and its association with cognitive function

Individuals with recent-onset psychosis (ROP) present widespread grey matter (GM) reductions and white matter (WM) abnormalities. However, relationships between GM and WM changes and their association with cognitive impairment, a key symptom of ROP, are unclear. Using a multiblock partial least squares correlation (MB-PLS-C) analysis, we examined multivariate GM-WM relationships and their association with cognitive abilities in ROP. We used T1 and diffusion-weighted images from 71 non-affective ROP individuals (age 22.1±3.2) and 71 matched controls. We performed MB-PLS-C between GM thickness and WM fractional anisotropy (FA) and between GM surface area and WM FA to identify multivariate GM-WM patterns and analysed correlations between these patterns and cognitive abilities. MB-PLS-C identified a 'GM thickness'-'WM FA' pattern representing group differences, explaining 12.38% of the variance and associated with frontal and temporal GM regions and seven WM tracts, including the corticospinal tract. MB-PLS-C also identified a 'GM surface area'-'WM FA' pattern showing group differences, explaining 18.92% and related with cingulate, frontal, temporal, and parietal GM regions and 15 WM tracts, including the inferior cerebellar peduncle. The 'GM thickness'-'WM FA' pattern describing group differences was significantly correlated with processing speed in ROP. There was no association between cognition and the 'GM surface area'-'WM FA' pattern. MB-PLS-C identified differential whole-brain GM-WM relationships, indicating a potential signature of brain alterations in ROP. Our findings of a relationship between cognitive function and GM-WM patterns for GM thickness rather than for surface area have implications for our understanding of brain-behaviour relationships neurodevelopmentally in psychosis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement YS was supported by the Research Training Program Scholarship, Heiwa Nakajima Foundation scholarship, and Japan Student Services Organization Scholarship. CP was supported by a National Health and Medical Research Council (NHMRC) Investigator Grant (ID: 1196508) and NHMRC Program Grant (ID: 1150083). VC was supported by an NHMRC Investigator Grant (ID: 1177370) and University of Melbourne Dame Kate Campbell Fellowship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data that were originally located at:https://www.humanconnectome.org/study/human-connectome-project-for-early-psychosis and https://www.humanconnectome.org/study/hcp-lifespan-development I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Brain imaging and cognitive and clinical data from the Human Connectome Project for early psychosis can be requested from https://www.humanconnectome.org/study/human-connectome-project-for-early-psychosis. Brain imaging and cognitive data from the Human Connectome Project Development can be requested from https://www.humanconnectome.org/study/hcp-lifespan-development. Access to these datasets requires approval. Other data can be obtained from the corresponding author upon reasonable request.