Circuitry-Guided Smoking Cessation in Schizophrenia

In a double-blinded, randomized, parallel controlled design, patients with schizophrenia spectrum disorder will be exposed to active or sham repetitive transcranial magentic stimulation (TMS) which was guided by functional magnetic resonance image (MRI). Smoking reduction/cessation and brain functional connectivity changes will be assessed at baseline, different stages of rTMS and/or follow-ups.

Neuroimaging studies suggest that high rate of smoking in patients with schizophrenia may be due to an overlap of nicotine addiction related circuitries and schizophrenia related circuitries, such that schizophrenia impact some of the same circuitries that increase risks for severe nicotine addiction in general. Those identified overlapping circuitries have been linked to several key features of nicotine addiction and can be represented by resting state functional connectivities. Transcranial magnetic stimulation (TMS) provides a non-invasive means for altering brain electrical neural activity. TMS has been approved by FDA for treatment of depression. Other applications have not been approved but it has been used in a wide range of clinical research especially in neurology and psychiatry. There are preliminarily significant improvements in treatments of smoking cessation in schizophrenia using TMS with small samples, but those treatments are not robust in larger samples. The high inter-subject variability limits the efficacy of TMS treatment in schizophrenia patients. We aim to develop a TMS method targeting special brain circuits that are both smoking cessation and schizophrenia related. If the corresponding brain circuits were successfully modulated, the treatment efficacy will be significantly improved and schizophrenia patients will benefit from the TMS treatment of smoking cessation.

Eligibility Criteria:
Inclusion Criteria:

* Male and female between ages 18-60
* Ability to give written informed consent (age 18 or above)
* Smoking in the last one year or more and average cigarette per day ≥ 5 in the past 4 weeks.
* For patient participants, Evaluation to Sign Consent (ESC) above10.

Exclusion Criteria:

* Any history of seizures
* Had smoking cessation treatment, clinical trial, or nicotine replacements within the past four weeks.
* Significant alcohol or other drug use (substance dependence within 6 months or substance abuse within 1 month) other than nicotine or marijuana dependence.
* Any major medical illnesses that may affect normal brain functioning. Examples of these conditions include, but not limited to, stroke, CNS infection or tumor, other significant brain neurological conditions.
* Taking \> 400 mg clozapine/day
* Failed TMS screening questionnaire
* Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
* History of head injury with loss of consciousness over 10 minutes; history of brain surgery
* Can not refrain from using alcohol and/or marijuana 24 hours or more \& cigarette smoking one hour or more prior to experiments.
* Woman who is pregnant (child-bearing potential but not on contraceptive and missing menstrual period; or by self report; or by positive pregnancy test).