The Cerebellum

, Volume 17, Issue 2, pp 143–151 | Cite as

Psychosis in Spinocerebellar Ataxias: a Case Series and Study of Tyrosine Hydroxylase in Substantia Nigra

  • Katherine W. Turk
  • Margaret E. Flanagan
  • Samuel Josephson
  • C. Dirk Keene
  • Suman JayadevEmail author
  • Thomas D. Bird
Original Paper


Spinocerebellar ataxias are a genetically heterogeneous group of degenerative diseases typically characterized by progressive ataxia and to various degrees, neuropathy, amyotrophy, and ocular abnormalities. There is increasing evidence for non-motor manifestations associated with cerebellar syndromes including cognitive and psychiatric features. We studied a retrospective clinical case series of eight subjects with spinocerebellar ataxias (SCAs) 2, 3, 7, and 17, all displaying features of psychosis, and also measured tyrosine hydroxylase (TH) staining of the substantia nigra (SN) at autopsy, among four of the subjects. We hypothesized that increased dopamine production in the SN may underlie the pathophysiology of psychosis in SCAs, given evidence of increased dopamine production in the SN in schizophrenia, as measured by TH staining. We analyzed differences in TH staining between the SCA psychosis cohort (n = 4), a heterogeneous ataxic cohort without psychosis (n = 22), and non-diseased age- and sex-matched control group (n = 12). SCA subjects with psychosis did not differ significantly in TH staining versus ataxic cases without psychosis. There was, however, increased TH staining in the ataxic cohort with and without psychosis (n = 26), compared to non-diseased controls (n = 12). Psychotic features were similar across subjects, with the presence of delusions, paranoia, and auditory hallucinations. Our findings are preliminary because of small numbers of subjects and variable neuropathology; however, they suggest that psychosis is a clinical feature of SCAs and may be under-recognized. While the underlying pathophysiology remains to be fully established, it may be related to extra-cerebellar pathology, including a possible propensity for increased dopamine activity in the SN.


Spinocerebellar ataxia Psychosis Neuropathology Dopamine 


Compliance with Ethical Standards

This study was approved by the University of Washington Institutional Review Board. Informed consent was obtained from all individual participants included in the study.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki Declaration and its later amendments.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Katherine W. Turk
    • 1
    • 2
    • 3
  • Margaret E. Flanagan
    • 4
    • 5
  • Samuel Josephson
    • 4
  • C. Dirk Keene
    • 4
  • Suman Jayadev
    • 1
    Email author
  • Thomas D. Bird
    • 1
    • 6
  1. 1.Department of NeurologyUniversity of Washington School of MedicineSeattleUSA
  2. 2.Department of NeurologyVeterans Affairs Boston Healthcare SystemBostonUSA
  3. 3.Boston University School of MedicineBostonUSA
  4. 4.Department of NeuropathologyUniversity of Washington School of MedicineSeattleUSA
  5. 5.Department of PathologyStanford University School of MedicinePalo AltoUSA
  6. 6.Geriatric Research Education and Clinical CenterVeterans Affairs Puget Sound Healthcare SystemSeattleUSA

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