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Nat Commun. 2018 Sep 21;9(1):3836. doi: 10.1038/s41467-018-06350-7.

Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization.

Author information

1
Department of Psychology, Yale University, New Haven, CT, 06511, USA. hengyi.cao@yale.edu.
2
Department of Psychology, Yale University, New Haven, CT, 06511, USA.
3
Department of Psychology, University of California Los Angeles, Los Angeles, CA, 90095, USA.
4
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, 90095, USA.
5
Department of Psychiatry, University of Calgary, Calgary, T2N 1N4, Canada.
6
Departments of Radiology, Clinical Neuroscience and Psychiatry, University of Calgary, Calgary, T2N 1N4, Canada.
7
Department of Psychiatry, University of California San Diego, San Diego, CA, 92093, USA.
8
Department of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, 11004, USA.
9
Department of Psychiatry, University of California San Francisco, San Francisco, CA, 94143, USA.
10
Department of Psychiatry, Yale University, New Haven, CT, 06510, USA.
11
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, 27599, USA.
12
Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA.
13
Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, 92697, USA.
14
Department of Psychology, Emory University, Atlanta, GA, 30322, USA.
15
Department of Psychology, Yale University, New Haven, CT, 06511, USA. tyrone.cannon@yale.edu.
16
Department of Psychiatry, Yale University, New Haven, CT, 06510, USA. tyrone.cannon@yale.edu.

Abstract

Understanding the fundamental alterations in brain functioning that lead to psychotic disorders remains a major challenge in clinical neuroscience. In particular, it is unknown whether any state-independent biomarkers can potentially predict the onset of psychosis and distinguish patients from healthy controls, regardless of paradigm. Here, using multi-paradigm fMRI data from the North American Prodrome Longitudinal Study consortium, we show that individuals at clinical high risk for psychosis display an intrinsic "trait-like" abnormality in brain architecture characterized as increased connectivity in the cerebello-thalamo-cortical circuitry, a pattern that is significantly more pronounced among converters compared with non-converters. This alteration is significantly correlated with disorganization symptoms and predictive of time to conversion to psychosis. Moreover, using an independent clinical sample, we demonstrate that this hyperconnectivity pattern is reliably detected and specifically present in patients with schizophrenia. These findings implicate cerebello-thalamo-cortical hyperconnectivity as a robust state-independent neural signature for psychosis prediction and characterization.

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