About one-third of patients with schizophrenia fail to respond to first-line antipsychotics, which severely impacts quality of life and adds societal costs. Clozapine is currently the only approved treatment for treatment-resistant schizophrenia but is often delayed due to the lack of early identification methods. Biomarkers, particularly those involving the dopaminergic system, could enable earlier diagnosis. Dopamine function assessed via 18F-DOPA PET imaging shows promise in distinguishing responders from nonresponders but is limited by radiotracer availability. Neuromelanin-sensitive MRI (NM-MRI), which does not require radiotracers, has emerged as a potential alternative, capable of identifying treatment-resistant patients through substantia nigra and ventral tegmental area (SN-VTA) signal contrast ratios.

A recent study assessed NM-MRI’s ability to predict treatment response in first-episode patients with psychosis. Higher SN-VTA signal ratios were observed in responders compared to nonresponders, demonstrating moderate diagnostic ability. Despite these challenges, the study highlights the ventral SN’s role in dopamine dysfunction and advances understanding of treatment resistance.

Reference: Vano LJ, Veronese M, McCutcheon RA, Howes OD. Neuromelanin-Sensitive MRI: A Biomarker for Treatment-Resistant Schizophrenia? Am J Psychiatry. 2024;181(6):468-470. doi: 10.1176/appi.ajp.20240278.