Hippocampal pathology in individuals at ultra-high risk for psychosis: a multi-modal magnetic resonance study.

Abstract

Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24 months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippocampal volume, hippocampal T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippocampal volume in the at-risk group compared to comparison subjects regardless of later transition status; on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippocampal head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippocampus prior to the development of psychosis, but that they are limited to the left hippocampal head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder.

• Authors: Stephen J Wood, Damien Kennedy, Lisa J Phillips, Marc L Seal, Murat Yücel, Barnaby Nelson, Alison R Yung, Graeme Jackson, Patrick D McGorry, Dennis Velakoulis, Christos Pantelis
• Journal: NeuroImage (Neuroimage) Vol. 52 Issue 1 Pg. 62-8 (Aug 01 2010) ISSN: 1095-9572 [Electronic] United States
• PMID: 20399273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antipsychotic Agents

Topics

• Antipsychotic Agents (therapeutic use)
• Case-Control Studies
• Female
• Follow-Up Studies
• Functional Laterality
• Hippocampus (drug effects, metabolism, pathology)
• Humans
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy
• Male
• Organ Size
• Psychotic Disorders (drug therapy, metabolism, pathology)
• Risk
• Schizophrenia (drug therapy, metabolism, pathology)
• Temporal Lobe (drug effects, metabolism, pathology)
• Time Factors
• Young Adult