IMPORTANCE

Structural alterations in the hippocampus and other medial temporal lobe regions have been observed in schizophrenia. How these alterations and hippocampal subfields might differ across the psychosis spectrum remains unclear.

OBJECTIVES

To characterize medial temporal lobe structures, including hippocampal subfields, using magnetic resonance imaging and to examine their relation to psychosis and cognitive function across the psychosis spectrum.

DESIGN, SETTING, AND PARTICIPANTS: Case-control, cross-sectional neuroimaging study in a large series of probands with psychotic disorders and healthy volunteers as part of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Patients with psychotic disorders (schizophrenia, n = 219; schizoaffective disorder, n = 142; and psychotic bipolar disorder, n = 188) and healthy controls (n = 337) were recruited across ambulatory clinics at university health centers in the B-SNIP consortium.

MAIN OUTCOMES AND MEASURES

Medial temporal lobe and hippocampal subfields were quantified with an automated parcellation approach using FreeSurfer software. Memory and other cognitive parameters were assessed using standardized neuropsychological tests.

RESULTS

Hippocampal volume reductions were seen in all 3 diagnostic groups when compared with healthy controls; alterations in the entorhinal cortex and parahippocampal regions were limited to schizophrenia and schizoaffective disorders (P < .001). Smaller volumes across the hippocampal subfields were seen in all 3 psychotic disorders, with the most prominent differences being in cornu ammonis 2/3 (P < .001). Hippocampal volumes were positively correlated with psychosis severity, declarative memory, and overall cognitive performance (P < .05).

CONCLUSIONS AND RELEVANCE

Alterations in the hippocampus were evident across psychotic disorders. Hippocampal subfields that participate in memory-related processes supporting pattern separation and pattern completion might be abnormal and may underlie the pathophysiology of psychosis.