Accelerated TMS in Psychosis

This study is to determine the tolerability and efficacy of an accelerated schedule of Transcranial Magnetic Stimulation for treating symptoms of psychotic disorders such as schizophrenia.

The aim of this protocol is to test the hypothesis that 'accelerated' Transcranial Magnetic Stimulation (TMS) is safe and efficacious in the treatment of psychotic disorders. TMS is a neuromodulation technique that utilizes magnets to alter neuronal activity non-invasively. TMS has received FDA approval as a therapeutic intervention for multiple psychiatric disorders. Historically, these FDA approved treatments have consisted of daily sessions spread out over multiple weeks. "Accelerated" TMS protocols deliver multiple TMS sessions daily over a shorter time frame (e.g., one week). Evidence from dozens of studies across multiple disorders suggests that these protocols are safe and effective.

In this protocol we will test the hypothesis that a form of TMS previously used to treat symptoms of schizophrenia is safe and effective when delivered on an accelerated schedule. Participants in this trial will receive neuronavigated intermittent theta burst TMS targeted to personalized network targets on an accelerated schedule. Our primary outcomes will be to determine if delivering TMS on this schedule is as safe and easily tolerated as it is in other disorders.

Additional outcomes measured will be to test the impact of accelerated TMS on multiple clinical and cognitive measures as well as neuroimaging markers of symptom response.

Eligibility Criteria:
Inclusion Criteria:

* Age between 18-65 years
* Diagnosis of a psychotic disorder (i.e. schizophrenia or schizoaffective disorder) or have been identified as being at clinical high risk for developing a psychotic disorder.
* Must be able to read, speak and understand English
* Must be judged by study staff to be capable of completing the study procedures
* Participants will be in stable outpatient treatment with no recent (within the past 30 days) hospitalizations or changes in their medication regimens.

Exclusion Criteria:

* Diagnostic and Statistical Manual 5 diagnosis of moderate substance use disorder within the past month
* Medications will be reviewed by the PI and a decision about inclusion will be made based on the participant's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other central nervous system active drugs. Current published TMS guidelines do not preclude specific medications in the setting of TMS(Rossi et al., 2021)
* Conditions that might result in increased risks of side effects or complications from rTMS or MRI, including:

  * Intracranial pathology from a known genetic disorder (e.g., Neurofibromatosis 1, tuberous sclerosis) or from acquired neurologic disease (e.g. stroke, tumor), cerebral palsy, history of severe head injury, or significant dysmorphology;
  * History of fainting spells of unknown or undetermined etiology that might constitute seizures
  * History of multiple seizures or diagnosis of epilepsy
  * Any progressive (e.g., neurodegenerative) neurological disorder such as multiple sclerosis or Parkinson's disease
  * Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
  * Metal implants (excluding dental fillings) unless cleared by the responsible covering MD (i.e. MRI compatible joint replacement)
  * Pacemaker
  * Implanted medication pump
  * Vagal nerve stimulator
  * Deep brain stimulator or transcutaneous electric nerve stimulation unit
  * Ventriculo-peritoneal shunt
  * Signs of increased intracranial pressure
  * Intracranial lesion
  * History of head injury resulting in prolonged loss of consciousness (\>15minutes) or neurological sequelae
  * Pregnancy: All participants capable of becoming pregnant will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study.