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Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive–compulsive disorder

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Abstract

Neurobiological models have provided consistent evidence of the involvement of cortical–subcortical circuitry in obsessive–compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

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Acknowledgements

This work was supported by Grants no. 2009/51482-0 and 2011/21357-9 provided by the São Paulo Research Foundation (FAPESP) and the National Council of Technological and Scientific Development (CNPq), no. 476647/2010. Kátia Cristina de Oliveira was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES). We are grateful to the families that donated the brains for this study. We would like thank all the members of the Brain Bank of Brazilian Aging Study Group. We would also thank Eduardo Alho MD, PhD for his assistance when using the 3D reconstruction software, the support of the staff from the Department of Psychiatry, Psychosomatics and Psychotherapy of the Mental Health Center of the University Hospital Würzburg, and the following psychiatrists, who contributed to the OCS diagnosis: E. Serap Monkul, MD, Ricardo Toniolo, MD, Alexandre Gigante, MD, PhD, Ana Gabriela Hounie, MD, Ph.D., Roseli Gedanke Shavitt, MD, Ph.D., Antonio Carlos Lopes, MD, Ph.D., Juliana B Diniz, MD, Ph.D.

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Authors and Affiliations

  1. Brain Bank of the Brazilian Aging Brain Study Group and HCFMUSP-LIM 22, University of São Paulo Medical School, São Paulo, Brazil

    Katia Cristina de Oliveira, Lea Tenenholz Grinberg, Claudia Kimie Suemoto, Luzia Carreira Lima, Ana Tereza Di Lorenzo Alho, José Marcelo Farfel, Renata Eloah de Lucena Ferretti-Rebustini, Renata Elaine Paraizo Leite, Ariane Cristine Moretto, Alexandre Valotta da Silva, Ricardo Nitrini, Wilson Jacob-Filho, Helmut Heinsen & Carlos Augusto Pasqualucci

  2. Program Spectrum Disorders Obsessive-Compulsive Disorder (PROTOC), Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil

    Katia Cristina de Oliveira, Marcelo Queiroz Hoexter & Eurípedes Constantino Miguel

  3. Bipolar Disorder Research Program (PROMAN), Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil

    Katia Cristina de Oliveira, Fabiano Gonçalves Nery, Ariane Cristine Moretto & Beny Lafer

  4. Discipline of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil

    Claudia Kimie Suemoto, José Marcelo Farfel, Renata Elaine Paraizo Leite, Ricardo Nitrini & Wilson Jacob-Filho

  5. Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil

    Ricardo Nitrini

  6. LIM 23-Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil

    Helena Brentani

  7. Medical-Surgical Nursing Department, University of Sao Paulo School of Nursing, São Paulo, Brazil

    Renata Eloah de Lucena Ferretti-Rebustini

  8. National Institute of Developmental Psychiatry for Children and Adolescents, CNPq São Paulo, São Paulo, Brazil

    Helena Brentani & Eurípedes Constantino Miguel

  9. Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil

    Helena Brentani, Beny Lafer & Eurípedes Constantino Miguel

  10. Hospital Israelita Albert Einstein, Brain Institute, São Paulo, Brazil

    Ana Tereza Di Lorenzo Alho & Alexandre Valotta da Silva

  11. Department of Psychiatry, Psychosomatics and Psychotherapy, Mental Health Center, University Hospital Wuerzburg, Würzburg, Germany

    Katia Cristina de Oliveira, Ana Tereza Di Lorenzo Alho & Helmut Heinsen

  12. Department of Neurology, Memory and Aging Center, San Francisco, CA, USA

    Lea Tenenholz Grinberg

  13. Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 1° andar, sala 1353, São Paulo, SP, 01246-903, Brazil

    Katia Cristina de Oliveira & Carlos Augusto Pasqualucci

Authors
  1. Katia Cristina de Oliveira
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  2. Lea Tenenholz Grinberg
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  3. Marcelo Queiroz Hoexter
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  4. Helena Brentani
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  5. Claudia Kimie Suemoto
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  6. Fabiano Gonçalves Nery
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  8. Ana Tereza Di Lorenzo Alho
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  10. Renata Eloah de Lucena Ferretti-Rebustini
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  11. Renata Elaine Paraizo Leite
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  15. Eurípedes Constantino Miguel
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  17. Wilson Jacob-Filho
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  18. Helmut Heinsen
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  19. Carlos Augusto Pasqualucci
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Corresponding author

Correspondence to Katia Cristina de Oliveira.

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de Oliveira, K.C., Grinberg, L.T., Hoexter, M.Q. et al. Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive–compulsive disorder. Brain Struct Funct 224, 191–203 (2019). https://doi.org/10.1007/s00429-018-1752-8

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  • DOI: https://doi.org/10.1007/s00429-018-1752-8

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