Minimal evidence that untreated psychosis damages brain structures: a systematic review

A longer duration of untreated psychosis (DUP) is associated with poor outcomes in first-episode psychosis (FEP); however, it is unclear whether this is due to the effects of psychosis on brain structure. We systematically reviewed the literature on the association between the length of untreated psychosis and brain structure in first-episode psychosis.

We searched three electronic databases and conducted forward and backward citation searching to identify relevant papers. Studies were included if they: (1) included patients with a psychotic disorder who were treatment naïve or minimally treated; and (2) had correlated measures of DUP or duration of untreated illness (DUI) with structural measures.

We identified 48 studies that met the inclusion criteria. Forty-three examined the correlation between DUP and brain structure, and 19 examined the correlation between DUI and brain structure. There was evidence of significant associations in brain regions considered important in psychosis; however, the proportion of significant associations was low and the findings were inconsistent across studies. The majority of included studies were not primarily designed to examine whether DUP/DUI is correlated with brain structure, and there were methodological limitations in many studies that prevent drawing a strong conclusion.

To date, there is minimal evidence of an association between untreated psychosis and brain structure in FEP. Although the body of literature is substantial, there are few hypothesis-driven studies with a primary objective to answer this question. Future studies should be specifically designed to examine whether untreated psychosis has a deleterious effect on brain structure.