Neurobiological vulnerability to panic disorder

Principal Investigator:  Richard J. Maddock, M.D.

The panic response is an "alarm" mechanism which may have adaptive value in the face of threat.  However, in patients with panic disorder, this response repeatedly occurs at inappropriate times.  The regulatory web that governs this neurobiological process appears to be disordered.  Research in my laboratory attempts to elucidate the nature of this dysfunction using a variety of neuroscience methods, including cognitive, metabolic and pharmacological challenge studies and neuroimaging. Several lines of evidence suggest that panic patients respond abnormally to metabolic challenges that affect the regulation of brain pH, including sodium lactate infusions and CO2 inhalation.  Magnetic resonance spectroscopy studies in our lab have shown that panic patients consistently have an exaggerated increase in brain lactate during neuronal activation.  Future studies will test competing models of the mechanism and pathogenic significance of this brain metabolic abnormality in panic disorder.

Repetitive transcranial magnetic stimulation for treatment of bipolar depression

Principal Investigator:  Guohua Xia, M.D., Ph.D. 

This is an open-labeled pilot study on whether high frequency repetitive transcranial magnetic stimulation (rTMS) can be used to treat bipolar disorder. The data obtained will help to design a controlled trial for he efficacy of rTMS in treatment of bipolar depression. As a noninvasive technology, rTMS has been used to stimulate the brain by rapidly changing magnetic field via a coil placed on the intact scalp. Research shows rTMS provides promising antidepressant effect in the treatment of major depression. Several case reports have indicated rTMS would benefit bipolar depression patients. Based on published studies, this study hypothesizes that rTMS on the left dorsal prefrontal lobe will improve bipolar depression significantly and causes fewer side effects. Candidate patients with bipolar depression will be recruited after signing informed consent. Fifteen selected patients will be treated by 3 weeks of rTMS treatment and be followed at 2 weeks post-treatment. Patients will keep their current medications unless a medication causes significant decrease of seizure threshold or side effects.  They must be on the same dose of antidepressant medication for least 4weeks without improvement of symptoms before been screened into the study.  Mood and other observed mental status will be monitored by standard psychological scales.

A multicenter double-blind randomized controlled trial to explore the tolerability, safety and efficacy of H-coil deep transcranial magnetic stimulation (TMS) in subjects with major depressive disorder (MDD)

Principal Investigator:  Guohua Xia, M.D., Ph.D.

This study is a multicenter, randomized double blind, sham controlled study to evaluate the safety and efficacy of H-coil deep transcranial magnetic stimulation (dTMS) as a treatment for patients with medication-resistant major depressive disorder. Studies of repetitive transcranial magnetic stimulation (rTMS), typically using a figure-8 coil, have shown that stimulating superficial brain regions can be beneficial in treating major depression. Differing from traditional figure-8 coil, the H-coil is designed to stimulate deep brain regions related to motivation, reward, and pleasure. The study population will consist of patients with major depressive disorder who have failed adequate medication treatment or shown significant intolerance to medications. The study duration is 18 weeks with a 2 week period of weaning the patient off medication, followed by 4 weeks of 5 daily treatments and 12 weeks of biweekly treatments. Mood and mental state will be carefully monitored through standard psychological scales and rating during the drug taper-down and throughout treatment.