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Research paper
Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy
  1. James Allebone1,2,
  2. Richard Kanaan2,3,
  3. Jerome Maller4,5,
  4. Terry O'Brien6,7,
  5. Saul Alator Mullen2,
  6. Mark Cook8,
  7. Sophia J Adams6,
  8. Simon Vogrin9,
  9. David N Vaughan2,10,
  10. Alan Connelly2,10,
  11. Patrick Kwan6,7,
  12. S F Berkovic10,
  13. Wendyl J D'Souza11,
  14. Graeme Jackson2,10,
  15. Dennis Velakoulis12,13,
  16. Sarah J Wilson1,2,10
  1. 1 Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia
  2. 2 The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
  3. 3 Department of Psychiatry, Austin Health, University of Melbourne, Melbourne, Australia
  4. 4 ANU College of Health and Medicine, Australian National University, Canberra, Victoria, Australia
  5. 5 Monash Alfred Psychiatry Research Centre, The Alfred and Monash University, Melbourne, Australia
  6. 6 Royal Melbourne Hospital, Melbourne, Victoria, Australia
  7. 7 Department of Neuroscience, Alfred Hospital, Monash University, Melbourne, Australia
  8. 8 Graeme Clark Institute, University of Melbourne, Melbourne, Australia
  9. 9 St Vincent's Hospital, Melbourne, Victoria, Australia
  10. 10 Comprehensive Epilepsy Program, Austin Health, University of Melbourne, Victoria, Australia
  11. 11 Department of Medicine, St Vincent's Hospital, The University of Melbourne, Australia
  12. 12 Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  13. 13 Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia
  1. Correspondence to James Allebone, Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia; james.allebone{at}


Objective Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research.

Methods In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP).

Results Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups.

Conclusion Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.

  • epilepsy
  • psychosis
  • hippocampus
  • postictal psychosis
  • interictal psychosis
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  • Contributors JA: study concept and design, acquisition of data, analysis and interpretation of data, drafting and critical revision of the manuscript for intellectual content. RK, JM, SJW, TOB, SAM, MC, SJA, SV, DV, AC, PK, SFB, WDS, GJ and SV: study concept and design, critical revision of the manuscript for intellectual content.

  • Funding JA is supported by an Australian Postgraduate Award.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Both study arms were approved by the Human Research Ethics Committees at The Royal Melbourne Hospital, Austin Health and St Vincent's Hospital Melbourne, Australia. All participants in the prospective arm of the study provided informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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