Longitudinal hippocampal subfield development associated with psychotic experiences in young people

Abstract

Abstract Hippocampal volumetric reductions are observed across the psychosis spectrum, with interest in the localisation of these reductions within the hippocampal subfields increasing. Deficits of the CA1 subfield in particular have been implicated in the neuropathophysiology of psychotic disorders. Investigating the trajectory of these abnormalities in healthy adolescents repoting sub-threshold psychotic experiences (PE) can provide insight into the neural mechanisms underlying psychotic symptoms without the potentially confounding effects of a formal disorder, or antipsychotic medication. In this novel investigation, a sample of 211 young people aged 11–13 participated initially in the Adolescent Brain Development study. PE classification was determined by expert consensus at each timepoint. Participants underwent neuroimaging at 3 timepoints, over 6 years. 78 participants with at least one scan were included in the final sample; 33 who met criteria for a definite PE at least once across all the timepoints (PE group), and 45 controls. Data from bilateral subfields of interest (CA1, CA2/3, CA4/DG, presubiculum, and subiculum) were extracted for Linear Mixed Effects analyses. Right CA1 (p = 0.047), and right CA2/3 subfields (p = 0.015) displayed group by time interaction effects (subfield volume increased in the control group, and decreased in the PE group). Left presubiculum volumes were significantly reduced in the PE group compared to controls, regardless of time (p = 0.023). These findings provide novel evidence implicating hippocampal subfield abnormalities in the pathophysiology underlying psychotic experiences. The CA1 particularly may be a key indicator of vulnerability for psychosis symptomology.