Patients with an at-risk mental state for psychosis gradually lost hippocampal volume as analyzed with MRI even though only about half of them progressed to full psychosis, according to a longitudinal study published in Schizophrenia Research.

Among the 18 patients who were prospectively followed, no significant differences in hippocampal volume loss were noted between those who transitioned and those who did not, reported Dr. Anna Walter and her associates at University of Basel and University Hospital Basel in Switzerland (Schizophr. Res. 2012 Nov. 5 [doi: 10.1016/j.schres.2012.10.013]).

The longitudinal study examined the extent to which hippocampal volume changes in antipsychotic-naive individuals with an at-risk mental state at the early stages of psychosis. The researchers expected to find decreases in hippocampal volume because past research has shown gray matter volume reductions in first-episode and chronic schizophrenia patients, but findings in patients with an at-risk mental state have been contradictory.

The 18 patients’ at-risk states were defined using Personal Assessment and Crisis Evaluation (PACE) by meeting at least one of three criteria: attenuated psychotic symptoms, brief limited intermittent psychotic symptoms, or a first-degree relative with a psychotic disorder, as well as two indicators in the patient of a clinical change. None had a previous psychotic disorder, borderline personality disorder, or a substance abuse problem, and none had symptoms that clearly derived from an organic disorder. Though none had taken antipsychotics, some had taken antidepressants.

The patients received MRI head scans at intake that included measurement of whole brain volume to allow for correction of head size differences. They were assessed with the Brief Psychiatric Rating Scale (BPRS) each month during the first year of the study, and every 3 months in the second and third years. They were assessed annually in subsequent years until the end of May 2007 or until they transitioned to psychosis, defined with ICD-10 research criteria and confirmed 1 year later. Average follow-up time was 5 years.

Patients were scanned a second time after transitioning to psychosis or at the end of follow-up (1,178 ± 501 days for transitioning patients; 1,541 ± 224 days for nontransitioning). To analyze hippocampal volume, the researchers used a “linear mixed effects model that included a random intercept factor for the subjects and fixed effects for time, hemisphere, age, medication, [whole brain volume] (at baseline) and time by hemisphere interaction.”

Although no significant differences existed between those who transitioned to psychosis and those who did not in terms of age, sex, baseline education, and interscan-interval, those who transitioned did trend toward comparatively higher scores at baseline on BPRS and the Scale for the Assessment of Negative Symptoms (SANS).

By the time of follow-up scans, five patients had begun taking antipsychotics; the others were all still antipsychotic naive. The scan analyses revealed a significant reduction in hippocampal volume over time in all the patients, but no statistical difference was found in the hippocampal changes across hemispheres despite a trend for smaller volume on the left side. Also, no statistically significant differences were found in the hippocampal volume reductions between the patients who transitioned and those who did not, showing no “progressive disease-stage related decrease of [hippocampal volume].”

In the second scans of the transitioned patients who had begun taking antipsychotics, the researchers found the drugs were associated with increased hippocampal volume. However, no links between hippocampal volume changes and symptoms (compared to baseline symptoms on BPRS and SANS) appeared, even after accounting for whole brain volume.

The study was funded by a Swiss National Science Foundation grant, and the authors declared no conflicts of interest.