TY - JOUR T1 - Mapping Brain-Behavior Space Relationships Along the Psychosis Spectrum JF - bioRxiv DO - 10.1101/2020.09.15.267310 SP - 2020.09.15.267310 AU - Jie Lisa Ji AU - Markus Helmer AU - Clara Fonteneau AU - Joshua B. Burt AU - Zailyn Tamayo AU - Jure Demšar AU - Brendan Adkinson AU - Aleksandar Savić AU - Katrin H. Preller AU - Flora Moujaes AU - Franz X. Vollenweider AU - William J. Martin AU - Grega Repovš AU - John D. Murray AU - Alan Anticevic Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/14/2020.09.15.267310.abstract N2 - Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically-grounded mapping between neural and symptom variation. This gap is particularly acute for psychosis-spectrum disorders (PSD). Here, in a sample of 436 cross-diagnostic PSD patients, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. In turn, these symptom axes mapped onto distinct, reproducible brain maps. Critically, we found that multivariate brain-behavior mapping techniques (e.g. canonical correlation analysis) do not produce stable results. Instead, we show that a univariate brain-behavioral space (BBS) can resolve stable individualized prediction. Finally, we show a proof-of-principle framework for relating personalized BBS metrics with molecular targets via serotonin and glutamate receptor manipulations and gene expression maps. Collectively, these results highlight a stable and data-driven BBS mapping across PSD, which offers an actionable path that can be iteratively optimized for personalized clinical biomarker endpoints.Competing Interest StatementJ.L.J., C.F., J.B.B., G.R., Z.T., J.D., and J.D.M. consult for BlackThorn Therapeutics. A.A. consulted for and was a SAB member for BlackThorn Therapeutics Inc. J.B.B. is an employee of RBNC Therapeutics. W.J.M. is an employee of The Janssen Pharmaceutical Companies of Johnson \& Johnson. J.L.J, J.D.M., and A.A. are co-inventors for the following pending patent: Anticevic A, Murray JD, Ji JL: Systems and Methods for Neuro-Behavioral Relationships in Dimensional Geometric Embedding (N-BRIDGE), PCT International Application No. PCT/US2119/022110, filed March 13, 2019. J.D.M., A.A., and W.J.M. are co-inventors for the following pending patent: Murray JD, Anticevic A, Martin, WJ: Methods and tools for detecting, diagnosing, predicting, prognosticating, or treating a neurobehavioral phenotype in a subject, U.S. Application No. 16/149,903 filed on October 2, 2018, U.S. Application or PCT International Application No. 18/054,009 filed on October 2, 2018. ER -