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Deep Brain Stimulation of the Substantia Nigra Pars Reticulata for Treatment-Resistant Schizophrenia: A Case Report

  • Nicola Cascella
    Correspondence
    Address correspondence to Nicola Cascella, M.D.
    Affiliations
    Johns Hopkins Schizophrenia Center, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland

    Department of Psychiatry, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Ankur A. Butala
    Affiliations
    Department of Psychiatry, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland

    Department of Neurology, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Kelly Mills
    Affiliations
    Department of Neurology, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Min Jae Kim
    Affiliations
    Department of Neurology, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Yousef Salimpour
    Affiliations
    Department of Neurology, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Teresa Wojtasievicz
    Affiliations
    Department of Neurosurgery, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Brian Hwang
    Affiliations
    Department of Neurosurgery, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Bernadette Cullen
    Affiliations
    Department of Psychiatry, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Martijn Figee
    Affiliations
    Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine, New York, New York
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  • Lauren Moran
    Affiliations
    Division of Psychotic Disorders, McLean Hospital, Belmont, Massachusetts
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  • Fred Lenz
    Affiliations
    Department of Neurosurgery, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • Akira Sawa
    Affiliations
    Johns Hopkins Schizophrenia Center, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland

    Department of Psychiatry, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland

    Department of Neuroscience, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland

    Department of Biomedical Engineering, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland

    Department of Mental Health, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • David J. Schretlen
    Affiliations
    Department of Psychiatry, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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  • William Anderson
    Affiliations
    Department of Neurosurgery, Johns Hopkins Hospital, the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland
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      Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease (
      • Mansouri A.
      • Taslimi S.
      • Badhiwala J.H.
      • Witiw C.D.
      • Nassiri F.
      • Odekerken V.J.J.
      • et al.
      Deep brain stimulation for Parkinson’s disease: Meta-analysis of results of randomized trials at varying lengths of follow-up.
      ) via modulation of motor corticostriatothalamic circuits (CSTs) (
      • Ashkan K.
      • Rogers P.
      • Bergman H.
      • Ughratdar I.
      Insights into the mechanisms of deep brain stimulation.
      ,
      • Herrington T.M.
      • Cheng J.J.
      • Eskandar E.N.
      Mechanisms of deep brain stimulation.
      ). CST connections to motor, limbic, and associative cortices are also promising DBS targets for Tourette syndrome, obsessive-compulsive disorder (
      • Naesstrom M.
      • Blomstedt P.
      • Bodlund O.
      A systematic review of psychiatric indications for deep brain stimulation, with focus on major depressive and obsessive-compulsive disorder.
      ), and major depression (
      • Alexander G.E.
      • DeLong M.R.
      • Strick P.L.
      Parallel organization of functionally segregated circuits linking basal ganglia and cortex.
      ,
      • Redgrave P.
      • Rodriguez M.
      • Smith Y.
      • Rodriguez-Oroz M.C.
      • Lehericy S.
      • Bergman H.
      • et al.
      Goal-directed and habitual control in the basal ganglia: Implications for Parkinson’s disease.
      ,
      • Tremblay L.
      • Worbe Y.
      • Thobois S.
      • Sgambato-Faure V.
      • Feger J.
      Selective dysfunction of basal ganglia subterritories: From movement to behavioral disorders.
      ,
      • Butala A.
      • Shepard M.
      • Pontone G.
      Neuropsychiatric aspects of Parkinson disease psychopharmacology: Insights from circuit dynamics.
      ). Schizophrenia (SZ) is a disorder with disruptions in limbic and associative CSTs (
      • Lewis D.A.
      • Sweet R.A.
      Schizophrenia from a neural circuitry perspective: Advancing toward rational pharmacological therapies.
      ,
      • Gault J.M.
      • Davis R.
      • Cascella N.G.
      • Saks E.R.
      • Corripio-Collado I.
      • Anderson W.S.
      • et al.
      Approaches to neuromodulation for schizophrenia.
      ). One-fifth to one-half of SZ patients are treatment resistant (TR). DBS targeted at basal ganglia structures within limbic and associative CSTs could have the potential to alleviate TR SZ symptoms. The substantia nigra pars reticulata (SNr) functions as a major basal ganglia output of limbic and associative CSTs via ascending projections to the mediodorsal nucleus of the thalamus and limbic and associative cortices, ultimately closing the loop via descending inhibitory GABAergic (gamma-aminobutyric acidergic) projections to the ventral basal ganglia and SNr (
      • Yoon J.H.
      • Minzenberg M.J.
      • Ursu S.
      • Walter B.S.R.
      • Wendelken C.
      • Ragland J.D.
      • Carter C.S.
      Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: Relationship with impaired cognition, behavioral disorganization, and global function.
      ,
      • Sakurai T.
      • Gamo N.J.
      • Hikida T.
      • Kim S.H.
      • Murai T.
      • Tomoda T.
      • et al.
      Converging models of schizophrenia--Network alterations of prefrontal cortex underlying cognitive impairments.
      ,
      • Parnaudeau S.
      • Bolkan S.S.
      • Kellendonk C.
      The mediodorsal thalamus: An essential partner of the prefrontal cortex for cognition.
      ). We postulated that the SNr may serve as a common node, modulating limbic and associative cortices through a projection to the mediodorsal nucleus of the thalamus. If so, this would make it a potentially effective target for DBS in TR SZ.
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      Linked Article

      • Erratum
        Biological PsychiatryVol. 90Issue 10
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          Erratum to: “Deep Brain Stimulation of the Substantia Nigra Pars Reticulata for Treatment-Resistant Schizophrenia: A Case Report,” by Cascella et al. (Biol Psychiatry 2021; 90:e57–e59); https://doi.org/10.1016/j.biopsych.2021.03.007 .
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