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Review
Approaches to neuromodulation for schizophrenia
  1. Judith M Gault1,2,
  2. Rachel Davis2,
  3. Nicola G Cascella3,
  4. Elyn R Saks4,
  5. Iluminada Corripio-Collado5,6,
  6. William S Anderson7,
  7. Ann Olincy2,
  8. John A Thompson1,
  9. Edith Pomarol-Clotet8,
  10. Akira Sawa3,
  11. Zafiris J Daskalakis9,
  12. Nir Lipsman10,
  13. Aviva Abosch1,11
  1. 1 Department of Neurosurgery, University of Colorado at Denver Anschutz Medical Campus, Aurora, Colorado, USA
  2. 2 Department of Psychiatry, University of Colorado Anschutz Medical Center, Aurora, Colorado, USA
  3. 3 Department of Psychiatry, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  4. 4 University of Southern California Law School, Los Angeles, California, USA
  5. 5 Psychiatric Department, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
  6. 6 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
  7. 7 Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland, USA
  8. 8 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
  9. 9 Centre for Addiction and Mental Health Collaborative Program in Neuroscience, University of Toronto, Toronto, Ontario, Canada
  10. 10 Division of Neurosurgery, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
  11. 11 Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
  1. Correspondence to Dr Judith M Gault, Department of Neurosurgery, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045-0508, USA; judith.gault{at}ucdenver.edu

Abstract

Based on the success of deep brain stimulation (DBS) for treating movement disorders, there is growing interest in using DBS to treat schizophrenia (SZ). We review the unmet needs of patients with SZ and the scientific rationale behind the DBS targets proposed in the literature in order to guide future development of DBS to treat this vulnerable patient population. SZ remains a devastating disorder despite treatment. Relapse, untreated psychosis, intolerable side effects and the lack of effective treatment for negative and cognitive symptoms contribute to poor outcome. Novel therapeutic interventions are needed to treat SZ and DBS is emerging as a potential intervention. Convergent genetic, pharmacological and neuroimaging evidence implicating neuropathology associated with psychosis is consistent with SZ being a circuit disorder amenable to striatal modulation with DBS. Many of the DBS targets proposed in the literature may modulate striatal dysregulation. Additional targets are considered for treating tardive dyskinesia and negative and cognitive symptoms. A need is identified for the concurrent development of neurophysiological biomarkers relevant to SZ pathology in order to inform DBS targeting. Finally, we discuss the current clinical trials of DBS for SZ, and their ethical considerations. We conclude that patients with severe symptoms despite treatment must have the capacity to consent for a DBS clinical trial in which risks can be estimated, but benefit is not known. In addition, psychiatric populations should have access to the potential benefits of neurosurgical advances.

  • schizophrenia
  • psychiatry
  • neurosurgery
  • neuropsychiatry
  • electrical stimulation
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Footnotes

  • Contributors JMG: substantial contributions to the conception and design of the work, and the acquisition, analysis and interpretation of data; drafting the work (except the ethics section), revising the entire manuscript critically for important intellectual content; final approval of the version published; agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RD: final approval of the version published; drafting the ethics section and revising the entire manuscript critically for important intellectual content. NGC: final approval of the version published; drafting the Hopkins clinical trial section and revising the entire manuscript critically for important intellectual content. ERS, JD: final approval of the version published; contributed to the ethics section draft and critical revision; contributed to the video. ICC, EPC: final approval of the version published; drafting the Barcelona Spain clinical trial section and revising it critically for important intellectual content. WSA, JAT: final approval of the version published; revising the entire manuscript for important intellectual content; reviewed accuracy of figure 3 DBS targets. AO, AS: final approval of the version published; revising the entire manuscript for important intellectual content. ZJD, NL: final approval of the version published; revising the University of Toronto clinical trial for important intellectual content. AA: final approval of the version published; critically revised the entire manuscript for important intellectual content; agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding Funding for this work was provided through an Independent Investigator NARSAD Grant through the Brain and Behavior Research Foundation (Grant ID 23295, JMG) and NIH grant 1RC1MH088735.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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