A Real-World Observation of Antipsychotic Effects on Brain Volumes and Intrinsic Brain Activity in Schizophrenia

BACKGROUND: The confounding effects of antipsychotics that led to the inconsistencies of neuroimaging findings have long been the barriers to understanding the pathophysiology of schizophrenia (SZ). Although it is widely accepted that antipsychotics can alleviate psychotic symptoms during the early most acute phase, the longer-term effects of antipsychotics on the brain have been unclear. This study aims to look at the susceptibility of different imaging measures to longer-term medicated status through real-world observation. METHODS: We compared gray matter volume (GMV) with amplitude of low-frequency fluctuations (ALFFs) in 89 medicated-schizophrenia (med-SZ), 81 unmedicated-schizophrenia (unmed-SZ), and 235 healthy controls (HC), and the differences were explored for relationships between imaging modalities and clinical variables. We also analyzed age-related effects on GMV and ALFF values in the two patient groups (med-SZ and unmed-SZ). RESULTS: Med-SZ demonstrated less GMV in the prefrontal cortex, temporal lobe, cingulate gyri, and left insula than unmed-SZ and HC (p < 0.05, family-wise error corrected). Additionally, GMV loss correlated with psychiatric symptom relief in all SZ. However, medicated status did not influence ALFF values: all SZ showed increased ALFF in the anterior cerebrum and decreased ALFF in posterior visual cortices compared with HC (p < 0.05, family-wise error corrected). Age-related GMV effects were seen in all regions, which showed group-level differences except fusiform gyrus. No significant correlation was found between ALFF values and psychiatric symptoms. CONCLUSION: GMV loss appeared to be pronounced to longer-term antipsychotics, whereby imbalanced alterations in regional low-frequency fluctuations persisted unaffected by antipsychotic treatment. Our findings may help to understand the disease course of SZ and potentially identify a reliable neuroimaging feature for diagnosis.