Cellular and extracellular white matter alterations after childhood trauma experience in individuals with schizophrenia.

Background: Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al., 2023) and examined the impact of CT on hypothesized lower free water-corrected FA (FA) and higher extracellular free water (FW).

Method: Thirty-seven SZ and 129 healthy controls (HC) were grouped into the 'none/low' or 'high' CT group. All participants underwent diffusion-weighted magnetic resonance imaging. We performed tract-based spatial statistics to study the main effects of diagnostic group and CT, and the interaction between CT and diagnostic group across FA and FW.

Results: SZ displayed lower FA within the corpus callosum and corona radiata compared to HC ( < 0.05, Threshold-Free Cluster Enhancement (TFCE)). Independent of diagnosis, we observed lower FA ( < 0.05, TFCE) and higher FW ( < 0.05, TFCE) in both SZ and HC with high CT levels compared to SZ and HC with none or low CT levels. Furthermore, we did not identify an interaction between CT and diagnostic group ( > 0.05, TFCE).

Conclusions: These novel findings suggest that the impact of CT on lower FA may reflect cellular rather than extracellular alterations in established schizophrenia. This highlights the impact of CT on white matter microstructure, regardless of diagnostic status.