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Neuropathological changes in the substantia nigra in schizophrenia but not depression

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Abstract

Schizophrenia is a chronic, disabling neuropsychiatric disorder characterised by positive, negative and cognitive symptoms. The aetiology is not known, although genetic, imaging and pathological studies have implicated both neurodevelopmental and neurodegenerative processes. The substantia nigra is a basal ganglia nucleus responsible for the production of dopamine and projection of dopaminergic neurons to the striatum. The substantia nigra is implicated in schizophrenia as dopamine has been heavily implicated in the dopamine hypothesis of schizophrenia and the prevalent psychotic symptoms and the monoamine theory of depression, and is a target for the development of new therapies. Studies into the major dopamine delivery pathways in the brain will therefore provide a strong base in improving knowledge of these psychiatric disorders. This post-mortem study examines the cytoarchitecture of dopaminergic neurons of the substantia nigra in schizophrenia (n = 12) and depression (n = 13) compared to matched controls (n = 13). Measures of nucleolar volume, nuclear length and nuclear area were taken in patients with chronic schizophrenia and major depressive disorder against matched controls. Astrocyte density was decreased in schizophrenia compared to controls (p = 0.030), with no change in oligodendrocyte density observed. Significantly increased nuclear cross-sectional area (p = 0.017) and length (p = 0.021), and increased nucleolar volume (p = 0.037) in dopaminergic neurons were observed in schizophrenia patients compared with controls, suggesting nuclear pleomorphic changes. No changes were observed in depression cases compared to control group. These changes may reflect pathological alterations in gene expression, neuronal structure and function in schizophrenia.

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Acknowledgments

The authors would like to thank Prof. Steven Gentleman for neuropathological advice and Prof. Tim Crow for original review of the Runwell schizophrenia series. The tissue was obtained from the Corsellis collection, which is supported by the Starr foundation and the West London Mental Health Trust and the research supported by funding from the MRC-UK PET Methodology Programme Grant G1100809/1. This project was conducted under ethical permission granted by the London south west local ethics committee reference WL/02/12 (2002), and amendment WL/02/12/AM01 granted by the Ealing and WLMHT local research ethics committee (2006).

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Authors and Affiliations

  1. Institute of Psychiatry, King’s College London, De Crespigny Park, London, SE5 8AF, UK

    M. R. Williams, F. Turkheimer & O. D. Howes

  2. Neuropathology Unit, Division of Experimental Medicine, Imperial College London, Charing Cross Campus, St Dunstan’s Road, London, W6 8RP, UK

    M. R. Williams, K. Galvin, B. O’Sullivan, R. K. B. Pearce & S. R. Hirsch

  3. University Hospital Aintree, Fazakerley, L9 7AL, UK

    B. O’Sullivan

  4. Academic Neurosurgery Unit, St. George’s, University of London, London, UK

    C. D. MacDonald

  5. Li Ka Shing Faculty of Medicine, University of Hong Kong, Sassoon Road, Hong Kong, China

    E. W. K. Ching

  6. Psychiatric Imaging Group, MRC Clinical Science Centre, Imperial College Hammersmith Campus, London, W12 0NN, UK

    O. D. Howes

  7. Trust HQ, West London Mental Health NHS Trust, Uxbridge Road, Southall Middlesex, UB1 3EU, UK

    M. Maier

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Williams, M.R., Galvin, K., O’Sullivan, B. et al. Neuropathological changes in the substantia nigra in schizophrenia but not depression. Eur Arch Psychiatry Clin Neurosci 264, 285–296 (2014). https://doi.org/10.1007/s00406-013-0479-z

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