Mapping brain-behavior space relationships along the psychosis spectrum

Autor: Jie Lisa Ji, Markus Helmer, Clara Fonteneau, Joshua B Burt, Zailyn Tamayo, Jure Demšar, Brendan D Adkinson, Aleksandar Savić, Katrin H Preller, Flora Moujaes, Franz X Vollenweider, William J Martin, Grega Repovš, Youngsun T Cho, Christopher Pittenger, John D Murray, Alan Anticevic
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: eLife, Vol 10 (2021)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.66968
Popis: 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 PSD patients spanning several diagnoses, 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 with current sample sizes. However, 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 neural gene expression maps derived from the Allen Human Brain Atlas. 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.
Databáze: Directory of Open Access Journals