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Stereological investigation of the posterior hippocampus in affective disorders

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Hippocampus volumes have been shown to be decreased in patients with major depression, but volume measurements are inconsistent in patients with bipolar disorder. Both disorders are associated with deficits in hippocampus-mediated cognitive functions. However, the underlying pathophysiology is widely unknown. In this post-mortem study, we used design-based stereology on Nissl-stained serial sections to investigate the number of neurons, oligodendrocytes and astrocytes in substructures of the posterior hippocampus in eight patients with major depression, eight patients with bipolar disorder and ten control patients without a neuropsychiatric disorder. Compared to controls, patients with bipolar disorder had significantly more neurons in the cornu ammonis subfield 1 (CA1) and the subiculum, while the number of oligodendrocytes was higher only in CA1. In patients with major depression, the density of oligodendrocytes was higher in CA2/3, CA4 and the subiculum. The dose of antidepressants correlated with the density and number of oligodendrocytes in CA2/3, indicating that antidepressants may affect our results. Treatment with neuroleptics expressed in chlorpromazine equivalents and benzodiazepines expressed in diazepam equivalents correlated negatively with the number of oligodendrocytes in CA2/3 and CA4, respectively, suggesting that treatment with these drugs do not influence cell number. We did not detect alterations in either volumes of substructures or numbers of astrocytes. Increased cell numbers argue for a denser packing of neurons and oligodendrocytes as a result of a decreased neuropils. This neuropathological process may be based on neurodevelopmental disturbances and may contribute to altered microconnectivity and cognitive deficits in affective disorders.

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Acknowledgments

The study was supported by the European Community under the Sixth Framework Program (BrainNet Europe II, LSHM-CT-2004-503039). This paper reflects only the authors’ views, and the Community is not liable for any use that may be made of the information contained therein. The authors thank Jacquie Klesing, Board-certified Editor in the Life Sciences (ELS), for editing assistance with the manuscript.

Conflicts of interest

B. Malchow, S. Strocka, F. Frank, T. Schneider-Axmann, J. Steiner H.-G. Bernstein, B. Bogerts, C. Schmitz and D. Reich-Erkelenz declare no conflicts of interest. A. Hasan has been invited to scientific meetings by Lundbeck, Janssen-Cilag and Pfizer and received a paid speakership from Desitin. He is a member of the advisory board of Roche. A. Schmitt was honorary speaker for TAD Pharma and Roche and has been a member of advisory boards for Roche. P. Falkai has been a member of the advisory boards for Janssen-Cilag, BMS, Lundbeck, Pfizer, Lilly and AstraZeneca and received an educational grant from AstraZeneca and honoraria as a lecturer from Janssen-Cilag, BMS, Lundbeck, Pfizer, Lilly and AstraZeneca.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Nussbaumstrasse 7, 80336, Munich, Germany

    Berend Malchow, Thomas Schneider-Axmann, Alkomiet Hasan, Daniela Reich-Erkelenz, Peter Falkai & Andrea Schmitt

  2. Department of Psychiatry and Psychotherapy, University of Göttingen, Von-Siebold Str. 5, 37075, Göttingen, Germany

    Steffen Strocka & Friederike Frank

  3. Department of Diagnostic and Interventional Radiology, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany

    Steffen Strocka

  4. Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Hans-Gert Bernstein, Johann Steiner & Bernhard Bogerts

  5. Department of Neuroanatomy, Ludwig Maximilian University, Pettenkoferstrasse 11, 80336, Munich, Germany

    Christoph Schmitz

  6. Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of Sao Paulo, Rua Dr. Ovidio Pires de Campos 785, São Paulo, SP, 05453-010, Brazil

    Andrea Schmitt

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  1. Berend Malchow
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  3. Friederike Frank
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  4. Hans-Gert Bernstein
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  5. Johann Steiner
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  8. Daniela Reich-Erkelenz
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  10. Bernhard Bogerts
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  11. Peter Falkai
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  12. Andrea Schmitt
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Correspondence to Andrea Schmitt.

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Malchow, B., Strocka, S., Frank, F. et al. Stereological investigation of the posterior hippocampus in affective disorders. J Neural Transm 122, 1019–1033 (2015). https://doi.org/10.1007/s00702-014-1316-x

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