Altered intrinsic neural activity and its molecular analyses in first-episode schizophrenia with auditory verbal hallucinations.

Background: Auditory verbal hallucinations (AVHs) are one of the signature positive symptoms of schizophrenia, affecting a substantial portion of patients with schizophrenia. These hallucinations seriously impact the lives of patients, resulting in a substantial social burden. Recent studies have shown a significant correlation between abnormal local brain activity and the neurobiological mechanisms of AVHs. However, it is not fully clear whether altered intrinsic brain activity in schizophrenia patients with AVHs is correlated with specific neurotransmitter systems.

Methods: We included 50 first-episode, drug-naïve schizophrenia patients with AVHs, 50 patients without AVHs (NAVHs), and 50 age- and sex-matched healthy controls (HCs). The amplitude of low-frequency fluctuation (ALFF) was utilized to explore the altered intrinsic brain activity in the AVH group. Subsequently, we spatially correlated the altered ALFF with neurotransmitter maps using JuSpace.

Results: In our study, compared to HCs, the AVH group exhibited significantly reduced ALFF in multiple brain regions, mainly including the left precuneus, bilateral supplementary motor areas, bilateral paracentral lobules, bilateral precentral gyri, and bilateral postcentral gyri. The NAVH group showed significantly reduced ALFF in the left inferior occipital gyrus, left calcarine gyrus, and left lingual gyrus compared to HCs. Furthermore, the AVH group showed higher ALFF in the right inferior frontal gyrus compared to the NAVH group. Additionally, these ALFF alterations in the AVH group were closely related to three neurotransmitters, including dopamine, serotonin and norepinephrine.

Conclusion: We link neurotransmitters to abnormal intrinsic brain activity in first-episode, drug-naïve schizophrenia patients with AVHs, contributing to a comprehensive understanding of the pathophysiological processes and treatment pathways underlying AVHs.