Abstract
Auditory verbal hallucinations (AVHs) are experienced by the majority of patients with schizophrenia and are often resistant to treatment with antipsychotic agents. White matter (WM) tract abnormalities are associated with AVH treatment efficacy. Using a retrospective design, 115 patients with schizophrenia with AVHs, 48 with medication-resistant AVHs and 67 with treatable AVHs, and 70 healthy controls (HCs) were selected from the database of our cohort study for 5-year follow-up assessment. WM tract integrity was measured using tract-based spatial statistics (TBSS) at baseline and after 5 years of antipsychotic agent treatment. The fractional anisotropy (FA) value was used to demonstrate WM tract alterations in patients with schizophrenia with medication-resistant AVHs, in patients with schizophrenia with treatable AVHs, and in HCs. Our data demonstrated that medication-resistant patients showed significantly greater FA values in the corpus callosum (CC) fasciculus at baseline and in the corticospinal tract post-treatment compared to HCs, but the baseline difference in the CC fasciculus was no longer significant after 5 years of antipsychotic agent treatment. The medication-resistant AVH group exhibited greater FA values in the superior longitudinal fasciculus after 5 years of antipsychotic agent treatment. Compared to the HC group, the treatable AVH group exhibited significantly greater FA values in the visual radiation and CC after 5 years of antipsychotic agent treatment. In the medication-resistant and treatable groups, common WM tract abnormalities were noted, as greater FA values were observed in the CC group at baseline compared to the HC group. At the same time, distinct abnormalities were noted, as greater FA values were observed in the superior longitudinal fasciculus, which may contribute to medication-resistant AVHs, whereas abnormalities in the CC fasciculus may contribute to both treatable and medication-resistant AVHs. In the HCs, a decrease in FA values in the posterior CC was observed after 5 years of observation compared to baseline. In summary, patients with treatment-resistant AVHs with schizophrenia and patients with treatable AVHs with schizophrenia have common and distinct abnormalities in the WM tract.