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Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure

Molecular Psychiatry volume 26, pages 5407–5416 (2021)Cite this article

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Abstract

Incomplete hippocampal inversion (IHI) is an anatomical variant of the human brain resulting from an arrest in brain development, especially prevalent in the left hemisphere. We hypothesized that IHI is more common in schizophrenia and contributes to the well-known hippocampal structural differences. We studied 199 schizophrenia patients and 161 healthy control participants with 3 T MRI to establish IHI prevalence and the relationship of IHI with hippocampal volume and asymmetry. IHI was more prevalent (left hemisphere: 15% of healthy control participants, 27% of schizophrenia patients; right hemisphere: 4% of healthy control participants, 10% of schizophrenia patients) and more severe in schizophrenia patients compared to healthy control participants. Severe IHI cases were associated with a higher rate of automated segmentation failure. IHI contributed to smaller hippocampal volume and increased R > L volume asymmetry in schizophrenia. The increased prevalence and severity of IHI supports the neurodevelopmental model of schizophrenia. The impact of this developmental variant deserves further exploration in studies of the hippocampus in schizophrenia.

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Fig. 1: Incomplete hippocampal inversion.
Fig. 2: Distribution of IHI scores based on laterality of the hippocampus in both schizophrenia patients and healthy control participants.

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Acknowledgements

Research reported in this publication was supported by the Charlotte and Donald Test Fund, the National Institute of Health (NIMH) grants R01-MH70560 (SH), R01-MH102266 (NDW), and R01-MH123563 (SV), Jack Martin, MD Research Professor in Psychopharmacology (JUB), the Vanderbilt Psychiatric Genotype/Phenotype Project, and the Vanderbilt Institute for Clinical and Translational Research (through grant 1-UL-1-TR000445 from the National Center for Research Resources/NIH) and National Institute of Health (NIH) grant T32-GM007347 (MJR).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA

    Maxwell J. Roeske, Maureen McHugo, Jennifer Urbano Blackford, Neil D. Woodward & Stephan Heckers

  2. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    Simon Vandekar

  3. Research Health Scientist, Research and Development, Veterans Affairs Medical Center, Nashville, TN, USA

    Jennifer Urbano Blackford

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  1. Maxwell J. Roeske
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Correspondence to Maxwell J. Roeske.

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Roeske, M.J., McHugo, M., Vandekar, S. et al. Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure. Mol Psychiatry 26, 5407–5416 (2021). https://doi.org/10.1038/s41380-020-01010-z

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