Study Protocol: Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project
Authors: Wang Jun , Jiang Chenguang , Guo Zhenglin , Chapman Sinéad , Kozhemiako Nataliia , Mylonas Dimitrios , Su Yi , Zhou Lin , Shen Lu ,   the GRINS Consortium, Sun Yifan , Li Duxing , Huang Zixuan , Liu Jikang , Gai Guanchen , Zou Kai , Wang Zhe , Yu Xiaoman , Chen Limin , Gao Xuezheng , Wang Guoqiang , Zhu Wei , Wang Jess , Wang Lei A. , Wang Yining , Zhou Hongliang , Li Shen , Qin Shengying , Murphy Michael , Tan Shuping , Manoach Dara S. , Stickgold Robert , Huang Hailiang , Zhou Zhenhe , Purcell Shaun M. , Hall Meihua , Hyman Steven E. , Pan Jen Q. 
Published: June 2024

Abstract
Background
Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project.

Methods
The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain.

Conclusion
Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.