Neuropathological changes in the nucleus basalis in schizophrenia

  • M. R. Williams
  • R. Marsh
  • C. D. Macdonald
  • J. Jain
  • R. K. B. Pearce
  • S. R. Hirsch
  • O. Ansorge
  • S. M. Gentleman
  • M. Maier
Original Paper


The nucleus basalis has not been examined in detail in severe mental illness. Several studies have demonstrated decreases in glia and glial markers in the cerebral cortex in schizophrenia, familial bipolar disorder and recurrent depression. Changes in neocortical neuron size and shape have also been reported. The nucleus basalis is a collection of large cholinergic neurons in the basal forebrain receiving information from the midbrain and limbic system, projecting to the cortex and involved with attention, learning and memory, and receives regulation from serotonergic inputs. Forty-one cases aged 41–60 years with schizophrenia or major depressive disorder with age-matched controls were collected. Formalin-fixed paraffin-embedded coronal nucleus basalis sections were histologically stained for oligodendrocyte identification with cresyl-haematoxylin counterstain, for neuroarchitecture with differentiated cresyl violet stain and astrocytes were detected by glial fibrillary acid protein immunohistochemistry. Cell density and neuroarchitecture were measured using Image Pro Plus. There were larger NB oval neuron soma in the combined schizophrenia and major depression disorder groups (p = 0.038), with no significant change between controls and schizophrenia and major depression disorder separately. There is a significant reduction in oligodendrocyte density (p = 0.038) in the nucleus basalis in schizophrenia. The ratio of gemistocytic to fibrillary astrocytes showed a greater proportion of the former in schizophrenia (18.1 %) and major depressive disorder (39.9 %) than in controls (7.9 %). These results suggest glial cell abnormalities in the nucleus basalis in schizophrenia possibly leading to cortical-limbic disturbance and subcortical dysfunction.


Schizophrenia Neuropathology Glia Subcortical 



The authors would like to thank Dr. Federico Roncaroli for aid with dissection and Prof. Federico Turkheimer for advice on statistics. This work was funded by the Stanley foundation and MRC-UK PET Methodology Programme Grant G1100809/1. The tissue was obtained from the Corsellis collection, which is supported by the Starr foundation and the West London Mental Health Trust.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

406_2012_387_MOESM1_ESM.doc (738 kb)
Supplementary material 1 (DOC 738 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • M. R. Williams
    • 1
    • 2
  • R. Marsh
    • 2
  • C. D. Macdonald
    • 3
  • J. Jain
    • 4
    • 5
  • R. K. B. Pearce
    • 2
  • S. R. Hirsch
    • 2
  • O. Ansorge
    • 6
  • S. M. Gentleman
    • 2
  • M. Maier
    • 7
  1. 1.King’s College London, Institute of PsychiatryLondonUK
  2. 2.Neuropathology Unit, Department of MedicineImperial College London, Charing Cross HospitalLondonUK
  3. 3.Academic Neurosurgery UnitSt. George’s, University of LondonLondonUK
  4. 4.Department of BiologyJohns Hopkins UniversityBaltimoreUSA
  5. 5.Department of BiochemistryUniversity of OxfordOxfordUK
  6. 6.Department of NeuropathologyThe Radcliffe InfirmaryOxfordUK
  7. 7.Trust HQ, West London Mental Health NHS TrustSouthall, MiddlesexUK

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