A Systematic Review of Neuroimaging Biomarkers to Predict Antipsychotic Treatment Response

Background:Up to a third of patients with schizophrenia do not experience sufficient improvement of symptoms and functioning on their first two trials of antipsychotic medications. This is concerning as ineffective antipsychotic treatment early in psychotic illness can lead to exacerbations of psychotic symptoms that impair daily functioning – leading to worse long-term outcomes. Given the considerable burdens associated with psychosis, there is a clear need to identify successful treatments, earlier in the course of illness. Numerous efforts have been made to identify different biomarkers for predicting antipsychotic treatment responses for patients with psychotic disorders. However, there are no known published systematic reviews pulling available evidence on this topic together.Aims & Objectives:This systematic review aims to (1) showcase the breadth of work that has been conducted on neuroimaging markers of response to first-line medications for psychosis between 1980 and 2024, (2) highlight patterns in the literature that show promise for effective treatment stratification, and (3) present methodological considerations for future studies on this topic that will support progress towards the clinical implementation of evidence-informed treatment stratification strategies.Method:The methods for this review were informed by the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement (Page et al., 2021). A systematic search of three Ovid electronic databases (MEDLINE, PsycINFO, and EMBASE) was conducted in January 2024 to identify neurological biomarkers of antipsychotic treatment response in individuals presenting with psychosis.Results:In total, this review examined 51 different predictive biomarkers of antipsychotic treatment response across 140 studies. The biomarkers included six fMRI, five structural MRI, seven 1H-MRS, three diffusion MRI, eight resting state EEG, five ERP EEG, six PET, eight CT, and three SPECT biomarkers. Whilst a large volume of work on the topic of predictive biomarkers of antipsychotic treatment response has been conducted, this review highlights that the replication of study methods and findings across studies remains a key limitation in this area of research. That said, the the most promising biomarkers for treatment response appear to be those that directly assess dopaminergic or glutamatergic neurotransmitter systems.Discussion & Conclusions:A substantial amount of work has been done to find neuroimaging biomarkers of antipsychotic treatment response. However, comparable research methods needed in order to move forward.