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Department of Psychiatry and Behavioral Sciences

Department of Psychiatry and Behavioral Sciences

Anxiety and Mood Disorders

Neurobiological processes of 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.  Current 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 functional neuroimaging.  The most consistent cognitive finding in panic disorder is that such patients exhibit longer response latencies to emotionally salient words on various cognitive tasks, including color naming and lexical decision tasks.  FMRI studies in our lab have shown that emotionally salient words consistently activate the retrosplenial region of the posterior cingulate gyrus, and the right amygdala in normal subjects.  Differences in the brain response to such stimuli in panic patients may suggest brain regions implicated in the pathogenesis of panic disorder.  Comparative studies in panic disorder patients are undergoing data analysis.  Several lines of evidence suggest that panic patients respond abnormally to metabolic challenges which affect the regulation of pH, including sodium lactate infusions and CO2 inhalation.  In our lab we have shown that panic patients consistently have an exaggerated systemic lactic acid response to alkalosis.  More recently, Dager and colleagues have reported the same abnormality within the brains of panic patients.  Magnetic resonance spectroscopy studies of brain energy metabolism and pH regulation in response to metabolic challenges in panic patients are being planned to test competing models of the mechanism of this metabolic abnormality.

Causes and cures of anxiety disorders

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

Any comprehensive understanding of the pathogenesis of anxiety disorders must incorporate a biopsychosocial perspective, as elements from each domain can influence the onset, continuation, and recovery from these illnesses.  In addition to neuroscientific studies of anxiety disorders, our lab also conducts cognitive, clinical and treatment research, with a special emphasis on panic disorder and post traumatic stress disorder.  Current projects include studies of the effects of emotional stimuli on memory and attentional processes and hemispheric lateralization, diagnostic and treatment studies of underlying anxiety disorders in chest pain patients, studies of the relationship between parental representations and symptom patterns in anxiety patients, and ongoing clinical trials of new medications for anxiety disorders.

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.