Repetitive Transcranial Magnetic Stimulation for Treating Depression: A Functional Magnetic Resonance Imaging Study

This protocol, "Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depressive Disorder (MDD): A Functional Connectivity Magnetic Resonance Imaging (fcMRI) Study," is an open-label pilot treatment study. The purpose of the present protocol is to treat participants with a diagnosis of Major Depressive Disorder with 4 weeks of rTMS, performing fcMRI and EEG studies prior to and following treatment to determine if treatment response is related to changes in fcMRI and/or EEG results. The investigators hypothesize that patients who respond to treatment will display changes in functional connectivity patterns thought to be related to the occurrence of depressive symptoms.

Depression is accompanied by rumination that supports inwardly focused cognitive attention on negative events and emotions. There is evidence to indicate that one aspect of this ruminative behavior lies in an abnormal increase in intra-regional connectivity among elements of the default mode network (DMN). It is also widely recognized that depression is associated with disturbances of cognition that include deficits in attentional processing, including both reductions in processing speed and deficits in selective attentional processing that are considered a part of executive function. Thus, there is at least equal reason to believe that attention and executive control networks might show changes in intra-regional functional connectivity. Given the attentional deficits associated with MDD, we hypothesize that there will be a weakening of intra-network resting state BOLD functional connectivity (rs-fcMRI) in addition to the strengthened connectivity reported by others.Further, we suggest that these shifts in intra-regional connectivity extend to the well-recognized anti-correlated activity between these two networks and support the intrusion of introspective, ruminative thought on cognitive activities that require externally directed attention. To test this hypothesis, we will use fMRI resting state functional connectivity to examine shifts in network connectivity prior to and following rTMS treatment for depression.

Eligibility Criteria:
Inclusion Criteria:

SCREENING/DIAGNOSTIC REQUIREMENTS:

* Male or female outpatients, ages 18-50 (some literature has shown increasing cortical distance with age that may affect treatment outcome
* Hamilton Rating Scale of Depression (HRSD-24) \> 18
* New onset major depression or untreated recurrent major depression per DSM-IV-TR38 criteria.
* Not taking antidepressant medication or any other psychotropic medication
* Using an adequate contraceptive method
* Able to give informed consent
* Available for 4 weeks of daily therapy, working hours, Mon.-Fri.
* English-speaking

Exclusion Criteria:

DIAGNOSTIC EXCLUSIONS:

* Co-morbid psychiatric diagnosis of bipolar disorder, acute OCD, schizophrenia or schizoaffective or concurrent treatment with outpatient ECT, or personality disorder or MDD with suicidal ideation as determined by history and/or by P.I. examination requiring hospital admission or referral for acute care.
* Previous failure to respond to treatment with rTMS
* Failure to achieve satisfactory improvement in depression after two or more adequate trials of antidepressant medications.

MEDICAL EXCLUSIONS:

* Patients newly diagnosed with thyroid dysfunction
* History of drug and/or ETOH dependence
* History of seizures
* History of head injury with loss of consciousness \> 5 minutes
* Any implantable metal object in the skull or near their head
* Any implantable devices such as a cardiac pacemaker, vagal nerve stimulator, etc.
* Positive urine pregnancy test
* Severe migraine headaches uncontrolled with routine non-narcotic medication
* Any medical condition in the opinion of the Investigator that might confound the results of the study Contraindications to fcMRI procedure
* Intake of NSAIDS, narcotic or muscle relaxants within 72 hours of the fMRI protocol.
* Claustrophobia.
* Left-handedness (may influence cerebral cortical hemispheric dominance).
* Inability to tolerate, or medical contraindication to MRI testing (e.g. metal prostheses or implants, history of claustrophobia)

PROTOCOL SPECIFIC EXCLUSIONS:

* Unable to determine motor threshold for determining treatment dose with rTMS device
* Mini Mental Status Exam (MMSE)70 score \< 24.