Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Purpose of the study: Evaluate the effect of deep repetitive transcranial magnetic stimulation (deep rTMS; hereafter abbreviated as "dTMS") on synaptic density measured with positron emission tomography (PET) and the radiotracer [11C]UCB-J. We also seek to link plasticity changes in the regions targeted by the electric field (especially, the insula) to changes in the functioning of insula circuits and behavioral cigarette usage in patients with schizophrenia (SCZ).Importance of the study: This is the first study designed to directly evaluate the mechanism of action (MOA) of dTMS for smoking disruption in patients with SCZ. Patients with SCZ are a vulnerable population in high, immediate need of new smoking therapeutics for reducing premature morbidity and mortality.

Inclusion Criteria:Ages 18-60DSM-5 criteria for schizophreniform, schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified (NOS).DSM-5 diagnosis of nicotine use disorder with current daily smoking, and a desire to cut down or quit.Negative urine toxicology (other than cannabis) maintained throughout study participationFluent English SpeakerCapacity for informed consentExclusion Criteria:Clinically significant psychopathology other than schizophrenia, schizophreniform, schizoaffective disorder, or psychotic disorder NOSCurrent or past substance use disorder, except TUDCurrent use of smoking cessation medications/productsChange in schizophrenia medication within 4 weeksHospitalization in the last 3 monthsHistory of suicidal or homicidal tendenciesHistory of epilepsy, stroke, cerebral aneurysm, significant head injury resulting in >10 min loss of consciousness, movement disorder, clinically significant electrolyte abnormalities, or use of clozapine (seizure risks)Pregnancy or lactation (females)Lack of effective birth control (females)Contraindications to MRI or PETClinical Global Impressions (CGI) rating of 6 (severely ill) or 7 (extremely ill)PrisonersContraindications to dTMS*The FDA website currently states that the Brainsway device used in this study is contraindicated for patients who have "metallic objects or implanted stimulator devices in or near the head, including cochlear implants, deep brain stimulators, vagus nerve stimulators, other implanted electrodes or stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes." We will monitor the FDA guidelines and implement any changes to the inclusion/exclusion criteria based on their most updated recommendations.