Deep Brain Stimulation (DBS) neuromodulation for Schizophrenia

Hi, I'm Judy Gault. I'm a Research Associate Professor, engaged in schizophrenia research at the University of Colorado in the Departments of Neurosurgery and Psychiatry. Today's presentation is on deep brain stimulation and its use for neuromodulation in schizophrenia, specifically, treatment refractory schizophrenia.

So, the overview for my presentation for deep brain stimulation for schizophrenia is to first, go over the general characteristics of schizophrenia. Then, discuss the unmet needs in patients with schizophrenia, and in the treatment refractory population. Then, discuss whether this patient population is actually amenable to deep brain stimulation. Then, we'll ask the question of whether schizophrenia, is a circuit disorder like Parkinson's disease, and a central tremor, and dystonia. These are disorders that are currently being treated with deep brain stimulation, and we'll ask the question, is schizophrenia circuit disorder like these and therefore amenable to deep brain stimulation? If so, what are the targets? What are the risks? We need to discuss the ethics and when do the benefits outweigh the risks. The image is of a patient who actually has a deep brain stimulation unit implanted and you can see what it entails in terms of the leads and the connection to a neuromodulation pulse generator.

Schizophrenia has a lifetime prevalence of 1 percent. Most people are familiar with psychosis, the hallmark symptom of schizophrenia. But in addition patients may experience disabling negative symptoms, like being unable to initiate or sustain simple daily activities. Furthermore, cognition and cognitive deficits are a core feature of schizophrenia. The majority of patients demonstrate a relapsing and remitting course of psychotic symptoms where development of a closed loop deep brain stimulation system that adapts to symptoms severity would be particularly beneficial. Antipsychotics are the gold standard for treatment of psychosis. Examples include Clozapine and Risperidone. Nonetheless, about 33 percent of patients continue to experience severe psychotic symptoms despite antipsychotic treatment, and have less than 20 to 30 percent improvement in symptoms with antipsychotic treatment. You can see in the slide here, the colored bar across the top, that patients initially try out various antipsychotic medications and then they'll relapse and are often changed to other medications. Another reason for changing antipsychotic would be the presence of side effects that are intolerable. Also shown is a threshold for hospitalization. You can see where the black line indicating psychotic symptoms. When it gets high, indicating acute relapse of psychosis, that those would be points when the patient may be hospitalized. The patient goes through a progressive stage of illness where relapse is common. Maybe even once a year, there may be multiple hospitalizations and multiple antipsychotics may be tried. The symptom threshold shown in the slide can be changed depending on the person. So, a person with treatment refractory schizophrenia has actually shown here where the majority of the time the patient is actually experiencing psychotic symptoms despite treatment with anti psychotics. A person who is very responsive to antipsychotic treatment, the symptom threshold line would be increased and most of the time their symptoms wouldn't break through. During the residual part of the illness, the acute psychotic episodes become more widely spaced and person becomes more familiar with dealing with their chronic illness and their support groups. Their family members, and their psychiatrist, and team members at the mental health facility where they may be seen are more familiar with the routine of what an acute psychotic relapse looks like and how to intervene. So, while psychosis in general may improve during the course of illness, the negative and cognitive symptoms, if present, are more constant and fluctuate less acutely. So, it's worth noting that patients with schizophrenia are often diagnosed as young adults and go through this progressive stage of illness, marked by frequent relapses, and often requiring hospitalization and trying multiple different antipsychotics. Then, during the residual stage of illness, the patient relapses less often. But the point is that, it's a chronic illness and the disease burden continues throughout life and so an early intervention that was effective would significantly impact the patient's life. Furthermore, it's worth noting that even in treatment responsive patients, antipsychotics do not control negative or cognitive symptoms. Antipsychotics are effective at treating only the positive symptoms. So, this slide goes over the many unmet needs of patients with schizophrenia,