Grey matter microstructural alterations in schizophrenia patients with treatment-resistant auditory verbal hallucinations.

Treatment-resistant auditory verbal hallucinations (TRAVH) are a relatively prevalent and devastating symptom in patients with schizophrenia (SCZ). Even though their pathological mechanisms are poorly understood, they seem to differ from those underlying non-hallucinating SCZ. In this study, we characterise structural brain changes in SCZ patients with TRAVH. With respect to non-hallucinating patients and healthy controls, we studied macrostructural grey matter changes through cortical thickness and subcortical volumetric data. Additionally, we analysed microstructural differences across groups using intracortical and subcortical mean diffusivity data. This latter imaging metric has been claimed to detect incipient neuronal damage, as water can diffuse more freely in regions with reduced neural density. We found brain macrostructrural and microstructural alterations in SCZ patients with TRAVH (n = 29), both with respect to non-hallucinating (n = 20) patients and healthy controls (n = 27). Importantly, a microstructural -rather than a macrostructural- compromise was found in key brain regions such as the ventral ACC, the NAcc and the hippocampus. These microstructural alterations correlated, in turn, with clinical severity. TRAVH patients also showed accentuated age-related cortical deterioration and an abnormal longitudinal loss of cortical integrity over a one-year period. These findings highlight the potential role of microstructural imaging biomarkers in SCZ. Notably, they could be used both to detect and to monitor subtle grey matter alterations in critical brain regions such as deep brain stimulation targets. Moreover, our results support the existence of a more aggressive and active pathological mechanism in patients with TRAVH, providing new insight into the aetiology of this debilitating illness.