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Neurosci Biobehav Rev. 2016 Dec;71:680-690. doi: 10.1016/j.neubiorev.2016.10.007. Epub 2016 Oct 20.

Hippocampal volume in subjects at clinical high-risk for psychosis: A systematic review and meta-analysis.

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Psychiatric University Clinics (UPK) Basel, Basel, Switzerland. Electronic address:
Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.
Psychiatric University Clinics (UPK) Basel, Basel, Switzerland.
Department of Psychology, Yale University, New Haven, CT, United States.
Departments of Psychiatry, Psychology and Brain Research Institute, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, United States.
Center for Psychosis Treatment, Psychiatry Clinics Solothurn, Solothurn, Switzerland.
Medical Image Analysis Center, University of Basel, Basel, Switzerland.


Several magnetic resonance imaging studies have reported reductions in hippocampal volume in patients with psychosis. It is unclear whether structural abnormalities predate illness onset. We conducted a detailed, systematic literature search for studies reporting hippocampal volume in subjects with clinical high-risk, compared to healthy controls. The overall sample size comprised 1429 subjects. Meta-analysis revealed no difference for left, but a small, albeit significant, difference for right hippocampal volume, such that clinical high-risk patients had slightly smaller hippocampal volume than healthy controls (g=0.24, p=0.0418). Meta-regression indicated a moderating effect of manual tracing approach, due to one outlying site. The small difference on the right side did not remain significant (g=0.14, 95%CI=[-0.03-0.32], p=0.11) after removal of this outlier. This meta-analysis suggests that there is no reduction in hippocampal volume before transition to psychosis and hippocampal volume cannot be used as a biomarker in clinical high-risk individuals.


At-risk mental state; Biomarker; Clinical high-risk; Early detection; Hippocampus; Magnetic resonance imaging; Psychosis; Ultra high-risk

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