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Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis

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Abstract

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2 years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome.

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Data availability

The data of this study are available upon request from the corresponding author.

Code availability

The analysis code of this study are available upon request from the corresponding author.

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Funding

This research was supported by project grants (IDs: 970598 and 981112) and Program Grant (ID: 350241) from the National Health and Medical Research Council (NHMRC), Australia; the Ian Potter Foundation, Melbourne; Woods Family Trust, Melbourne; a Program Grant from the Victorian Health Promotion Foundation, Melbourne. C Pantelis was supported by NHMRC Senior Principal Research Fellowships (628386 and 1105825), and a Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Award (US; Grant ID: 18722). PD McGorry was supported by a NHMRC Senior Principal Research Fellowship, and a Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Award (US). AR Yung was supported by a NHMRC Principal Research Fellowship (1136829) and a National Institute of Health Research (NIHR) Senior Fellowship Award. Y Wang was supported by the China Scholarship Council. T Van Rheenen was supported by an NHMRC Early Career Fellowship (1088785). B Nelson was supported by an NHMRC Senior Research Fellowship (1137687). A Lin is supported by an NHMRC Career Development Fellowship (1148793). VL Cropley was supported by a NHMRC Investigator Grant (1177370), a Brain and Behavior Research Foundation (NARSAD) Young Investigator Award (21660), and a University of Melbourne Dame Kate Campbell Fellowship. Raymond Chan was supported by the National Key Research and Development Programme (2016YFC0906402).

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Authors and Affiliations

  1. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Level 3, Alan Gilbert Building, 161 Barry St, Carlton, Melbourne, VIC, 3053, Australia

    Ya Wang, Esmee E. Braam, Cassandra M. J. Wannan, Tamsyn E. Van Rheenen, Dennis Velakoulis, Christos Pantelis & Vanessa L. Cropley

  2. Neuropsychology and Applied Cognitive Neuroscience Lab, CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China

    Ya Wang & Raymond C. K. Chan

  3. Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia

    Tamsyn E. Van Rheenen & Vanessa L. Cropley

  4. Orygen, Melbourne, Australia

    Barnaby Nelson, Patrick D. McGorry, Alison R. Yung & Stephen J. Wood

  5. Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia

    Barnaby Nelson, Patrick D. McGorry, Alison R. Yung, Warrick J. Brewer, John Koutsogiannis & Stephen J. Wood

  6. School of Health Sciences, University of Manchester, Manchester, UK

    Alison R. Yung

  7. Telethon Kids Institute, The University of Western Australia, Perth, Australia

    Ashleigh Lin

  8. School of Psychology, University of Birmingham, Edgbaston, UK

    Stephen J. Wood

  9. Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne Health, Melbourne, Australia

    Dennis Velakoulis

  10. Florey Institute of Neuroscience and Mental Health, Melbourne, Australia

    Christos Pantelis

  11. Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Australia

    Alison R. Yung

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  1. Ya Wang
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Contributions

VLC and CP designed the study. DV, BN, PM, AY, AL, WB, JK, SW and CP were responsible for participant recruitment and assessment. YW, EB and VLC performed statistical analysis. All authors reviewed data analysis and data interpretation. YW and EB wrote the first draft, which was critically reviewed by VLC. All authors contributed to the review of and critical input to the manuscript and have approved the final manuscript.

Corresponding author

Correspondence to Vanessa L. Cropley.

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All authors declares that they have no competing interest.

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The local research and ethics committee in Melbourne, Australia, approved the study.

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Informed consent was provided by all participants.

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Wang, Y., Braam, E.E., Wannan, C.M.J. et al. Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis. Eur Arch Psychiatry Clin Neurosci 271, 1475–1485 (2021). https://doi.org/10.1007/s00406-021-01300-9

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