Schizophrenia is a chronic mental disorder affecting approximately 1% of the population worldwide with a high rate of disability (Charlson et al., 2018; Howes and Murray, 2014; Saha et al., 2005). Schizophrenia typically presents with positive, negative, and cognitive symptoms. While the cause of schizophrenia is unknown, studies have found that it may be a neurodevelopmental disorder caused by a combination of genetic, environmental, and psychosocial factors (Murray et al., 2017; Warrier et al., 2021).

Schizophrenia has long been hypothesized to be a disorder characterized partly by white matter (WM) abnormalities that alter brain structural connectivity (Vitolo et al., 2017). The WM microstructure can be investigated in vivo via diffusion magnetic resonance imaging (dMRI), a method that measures the diffusion of water molecules in tissue. A lifespan multi-stie dMRI study showed that widely distributed WM deficits emerge in abnormal development or display perturbed maturation at the early stage of schizophrenia (Cetin-Karayumak et al., 2019). Various studies explore clinical and cognitive perspectives on WM deficits in schizophrenia (Ohtani et al., 2014; Ohtani et al., 2015; Seitz-Holland et al., 2022). However, the field has not yet reached a consensus regarding environmental effects related to WM microstructure in schizophrenia.

Environmental factors, such as childhood trauma (ChT), play an important role in the pathophysiology of schizophrenia. ChT, also known as childhood adversity, defines stressful life events such as physical, sexual, emotional abuse and neglect (Bhavsar et al., 2019). Numerous studies have found that various ChT were associated with long-term mental health problems (Hailes et al., 2019; Rod et al., 2020) and an increased risk of earlier schizophrenia onset (İngeç and Evren Kılıçaslan, 2020; Varese et al., 2012).

A significant body of studies has found that ChT is associated with abnormal development of brain microstructural connectivity (Asmal et al., 2019; Daniels et al., 2013; McCarthy-Jones et al., 2018; Poletti et al., 2015; Stevelink et al., 2018). A study in persons with no psychotic disorder reported that individuals who reported high levels of ChT showed lower fractional anisotropy (FA) in several WM bundles (e.g., cingulum bundle, corona radiata, corpus callosum, etc.) (McCarthy-Jones et al., 2018). To date, four studies have explored potential links between ChT and WM deficits in persons with schizophrenia. Three of the four studies were cross-sectional studies, which reported a link between increased ChT and decreased FA, although the conclusion was not completely consistent (Asmal et al., 2019; Molina et al., 2018; Poletti et al., 2015). The only multicenter longitudinal study found no significant associations between FA and ChT at baseline; however, patients showed a greater decrease in FA over time than controls when exposed to higher levels of ChT (Domen et al., 2019). Although these four studies have obtained some satisfactory results, a larger sample size is still needed for repetition and verification in this field. In addition, the above studies also have some defects, such as no control group in the study or long-term drug treatment of the patients (Molina et al., 2018).

In the present study, we investigated WM integrity in participants with first-episode schizophrenia (FES) in a relatively large sample in a Chinese Han population. Tract-Based Spatial Statistics (TBSS) was used to investigate the changes in FA. We also further investigated the relationship between FA and ChT in the participants with FES. Based on the previous studies mentioned above, we hypothesize that ChT and impaired WM may contribute to the risk for onset of schizophrenia and further accelerate the progression of schizophrenia.