Schizophrenia Studies From China: How They Help Extend the Understanding of the Illness

This theme issue provides an overview of many of the major schizophrenia research initiatives that have developed in China over the past 2 decades. The pace of this effort has accelerated in recent years, increasing public awareness about the disorder and providing the larger scientific community with unique insights. This issue includes 7 reviews of work conducted in China, including studies of individuals at clinical high risk, in first episode, and in treatment-naïve patients with a history of chronic illness, from the perspectives of neuroimaging, analytic approaches, cognition, neurodevelopment, and funding patterns.

Among these studies, neuroimaging is the most commonly used approach to characterize the brain abnormalities in patients during different illness courses in vivo.¹ Instead of using standard neuroradiological visual inspection with magnetic resonance imaging (MRI) to identify actionable findings warranting immediate medical attention, the purpose is to use regional quantitative analysis of MRI features to localize distinctive alterations, typically smaller than being readily observed by visual image inspection, that can identify biologically distinct subgroups of a patient and predict and track drug effects with the long-term goal of enhancing treatment planning. This approach has yielded promising findings in many recent studies. These identified brain alterations, sometimes in combination with machine learning algorithms, have also been related to clinical symptoms, cognitive impairments, and treatment responses. Though replication and multi-phenotyping validation is needed before they could be regarded as reliable and clinically useful, neuroimaging, the best clinical method for evaluating the target organ of interest, is a major focus of schizophrenia research in China.

In addition to neuroimaging and engineering, studies of cognitive and motivational impairments are another area of growing research effort. For current studies with multi-phenotyping approaches, neuroimaging, cognition, and other clinical behaviors and molecular measures with blood were all collected and assessed.² In one of the reviews, an overview of the funding that supports schizophrenia research in China was provided, including funding from the national ministries to the local research departments, and a summary of the projects supported by the National Natural Science Foundation of China, one of the most important funders in China. We think information on how research is supported in China would be of interest to the larger research community.

Regarding the study samples, the findings in the antipsychotic-naïve first-episode schizophrenia and chronic but untreated patients from West China are of great value in specifying the brain regions where functional and anatomical abnormalities are seen at the illness onset, which are crucial for understanding the pathophysiology and providing biological information in relation to illness prognosis and treatment selection. Studies in these populations are rarely possible in the West. In developing countries including China, never-treated patients including long-term ill patients can still be identified in both rural and urban areas, though they are becoming less common. With these rare samples, 3 important findings were noted. First, the basal ganglia enlargement was found in untreated patients both at first episode³ and in the chronic stage,⁴ suggesting it is an effect of the illness itself and not an artifact of treatment. Second, schizophrenia may involve neuroprogressive changes in the prefrontal and temporal cortices specifically, which are not secondary to antipsychotic treatment and begin slowly at the early phase of the illness and become more prominent later in the course of illness.^4,5 Third, illness heterogeneity could be resolved in biological terms that might help shift the focus of drug development toward altering specific targeted biological processes in biologically defined patient groups instead of working to change complex behavioral features that represent the final common pathway of different illness mechanisms.⁶

There is also a review examining the evolution and future prospects of prevention based on evaluation for individuals at clinical high risk of psychosis, drawing insights from the Shanghai At-Risk for Psychosis study.⁷ It highlights the strengths and clinical applications of such interventions, underscoring their potential to revolutionize preventive care for clinically high-risk individuals and enhancing precision in interventions.

It is important to note the contribution made by Prof. John Adrian Sweeney, who passed away in 2023 but had continuous and productive collaboration for about 15 years with the study group of Huaxi MR Research Center, Department of Radiology, West China Hospital of Sichuan University. His most important work was dedicated to studies of antipsychotic-naïve first-episode schizophrenia and chronic but untreated schizophrenia. With his help and guidance, studies from this group have systematically characterized the anatomical and functional brain changes at the illness onset and their progressive trajectories without medication confounds, and longitudinal brain changes after short- and long-term antipsychotic medication.^1,8 Additionally, potential biological subtypes of patients with schizophrenia have been identified with neuroimaging metrics and epigenetic measures, along with their multi-phenotyping biological correlates,^9,10 and they are still under active investigation. Through his comforting wisdom and guidance, Prof. Sweeney made critical contributions to this work and guided and inspired the careers of many scientists. Organizing this issue was also his idea with the hope of enhancing international collaboration with work in China. At the same time, it is noteworthy that such international and memorable collaboration with the Department of Radiology, West China Hospital started as early as 1924, when the first X-ray machine was introduced in West China Hospital by a Canadian, Edward Corry Wilford. This year also marks the 100th anniversary of the Department of Radiology of West China Hospital.

Studies in China have offered unique populations as well as sample sizes that are difficult to achieve in the West. To advance the discovery, validation, and translation of biomarkers for schizophrenia, the methods that are adopted for data acquisition and analysis need to be optimized and standardized, and ideally be reduced to the most limited effort needed for translation into clinical practice. For multicenter studies, the ability to collect near-to-identical data across sites needs to be established. Some promising multicenter studies are also under active investigation for the abovementioned purpose, such as the MRI Biomarkers for Antipsychotic Treatment of Schizophrenia (M-BATS) Consortium from West China.¹¹

Together and separately, the reviews in this issue introduced studies from China from multiple perspectives. Nevertheless, much remains unknown about schizophrenia, and developing biomarkers for illness identification and treatment selection, as well as novel therapies, remains a significant challenge. Therefore, this issue also highlights the opportunities for researchers from and outside China to work together to make progress in understanding schizophrenia.

Acknowledgments

Dr Lui acknowledges the support from the Humboldt Foundation Friedrich Wilhelm Bessel Research Award and Chang Jiang Scholars (Program No. T2019069). Dr Wenjing Zhang consults with VeraSci.

References