Alterations in the hippocampus and thalamus in individuals at high risk for psychosis.

Stefan Borgwardt,Renata Smieskova,Anastasia Theodoridou,Karsten Heekeren,Anita Riecher-Rössler,Wulf Rössler,Fabienne Harrisberger,Anna Walter,Laura Egloff,Roman Buechler,Claudia Lenz,Undine E Lang,Andor E Simon,Diana Wotruba,Kerstin Bendfeldt

doi:10.1038/npjschz.2016.33

Abstract

Reduction in hippocampal volume is a hallmark of schizophrenia and already present in the clinical high-risk state. Nevertheless, other subcortical structures, such as the thalamus, amygdala and pallidum can differentiate schizophrenia patients from controls. We studied the role of hippocampal and subcortical structures in clinical high-risk individuals from two cohorts. High-resolution T1-weighted structural MRI brain scans of a total of 91 clinical high-risk individuals and 64 healthy controls were collected in two centers. The bilateral volume of the hippocampus, the thalamus, the caudate, the putamen, the pallidum, the amygdala, and the accumbens were automatically segmented using FSL-FIRST. A linear mixed-effects model and a prospective meta-analysis were applied to assess group-related volumetric differences. We report reduced hippocampal and thalamic volumes in clinical high-risk individuals compared to healthy controls. No volumetric alterations were detected for the caudate, the putamen, the pallidum, the amygdala, or the accumbens. Moreover, we found comparable medium effect sizes for group-related comparison of the thalamus in the two analytical methods. These findings underline the relevance of specific alterations in the hippocampal and subcortical volumes in the high-risk state. Further analyses may allow hippocampal and thalamic volumes to be used as biomarkers to predict psychosis.

Highlights

Structural brain alterations, as assessed with magnetic resonance imaging (MRI), are commonly reported in schizophrenia patients
With the linear mixed-effects (LME) model to account for different scanners, we found that the volumes of the hippocampus and thalamus were significantly smaller in antipsychotic-naive clinical high risk (CHR) individuals than in healthy controls (HC)
No between-group differences were observed for volumes of the caudate, putamen, pallidum, amygdala, and accumbens

Summary

Introduction

Structural brain alterations, as assessed with magnetic resonance imaging (MRI), are commonly reported in schizophrenia patients. The hippocampus and subcortical structures are involved in a variety of tasks, through their interconnection with cortical and other subcortical areas (e.g., learning and memory[6] and emotional or motivational processing[7]). Aspects of these neuronal brain circuits are at least in part impaired in schizophrenia as well as in the high-risk state already.[8,9] it has been shown that hippocampal and subcortical volumes are moderately to highly heritable in multiplex-multigenerational families affected with schizophrenia.[10]

Methods

Results

Conclusion