Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional neural signature for psychosis prediction and characterization.
Hengyi Cao,Oliver Y. Chén,Yoonho Chung,Jennifer K. Forsyth,Sarah McEwen,Dylan G. Gee,Carrie E. Bearden,Jean Addington,Bradley G. Goodyear,Kristin S. Cadenhead,Heline Mirzakhanian,Barbara A. Cornblatt,Ricardo E. Carrión,Daniel H. Mathalon,Thomas H. McGlashan,Diana O. Perkins,Aysenil Belger,Larry J. Seidman,Heidi W. Thermenos,Ming T. Tsuang,Theo G.M. van Erp,Elaine F. Walker,Stephan Hamann,Alan Anticevic,Scott W. Woods,Tyrone D. Cannon +25 more
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TLDR
It is discovered that increased neural connectivity in the cerebello-thalamo-cortical circuitry predicts psychosis in those at high risk, and is present in people with schizophrenia.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.read more
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TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
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