The Neurobiology of Duration of Untreated Psychosis: A Comprehensive Review

Authors

Anthony W Zoghbi
Jeffrey A Lieberman
Ragy R Girgis

Publication Date

1-1-2023

Journal

Molecular Psychiatry

DOI

10.1038/s41380-022-01718-0

PMID

35931757

PMCID

PMC10979514

PubMedCentral® Posted Date

3-29-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Humans, Brain, Cognitive Dysfunction, Psychotic Disorders, Temporal Lobe

Abstract

Duration of untreated psychosis (DUP) is defined as the time from the onset of psychotic symptoms until the first treatment. Studies have shown that longer DUP is associated with poorer response rates to antipsychotic medications and impaired cognition, yet the neurobiologic correlates of DUP are poorly understood. Moreover, it has been hypothesized that untreated psychosis may be neurotoxic. Here, we conducted a comprehensive review of studies that have examined the neurobiology of DUP. Specifically, we included studies that evaluated DUP using a range of neurobiologic and imaging techniques and identified 83 articles that met inclusion and exclusion criteria. Overall, 27 out of the total 83 studies (32.5%) reported a significant neurobiological correlate with DUP. These results provide evidence against the notion of psychosis as structurally or functionally neurotoxic on a global scale and suggest that specific regions of the brain, such as temporal regions, may be more vulnerable to the effects of DUP. It is also possible that current methodologies lack the resolution needed to more accurately examine the effects of DUP on the brain, such as effects on synaptic density. Newer methodologies, such as MR scanners with stronger magnets, PET imaging with newer ligands capable of measuring subcellular structures (e.g., the PET ligand [11C]UCB-J) may be better able to capture these limited neuropathologic processes. Lastly, to ensure robust and replicable results, future studies of DUP should be adequately powered and specifically designed to test for the effects of DUP on localized brain structure and function with careful attention paid to potential confounds and methodological issues.