Research

Under the leadership of Dr. James F. Leckman, the research group has secured several federal and private grants to study the causes and treatment of Tourette syndrome (TS), obsessive-compulsive disorder (OCD), attention deficit-hyperactivity disorder (ADHD), and related childhood psychiatric disorders. In order to further our understanding of these disorders, we obtain a comprehensive set of data on all subjects, which allows a multidimensional analysis. Listed below are some of the primary studies underway as part of this effort.

Genetic Studies of Tourette Syndrome

In Progress.

Behavior Therapy for Adults and Adolescents with TS

We are recruiting subjects for a study of behavior therapy for tics. The purpose of this study is to evaluate whether a form of behavior therapy called Comprehensive Behavioral Intervention for Tics (CBIT) is helpful for reducing tics. CBIT will be compared to Psychoeducational Supportive Therapy (PST) and participants of this study will be randomly assigned (like the flip of a coin) to receive CBIT or PST.

Comprehensive Behavioral Intervention for Tics (CBIT) therapy consists of eight one-hour long treatment sessions scheduled over ten weeks. During this treatment, participants with learn to monitor their tics and will practice simple behavioral response that may make the tics less frequent or bothersome. Psychoeducational Supportive Therapy (PST) will also consist of eight one-hour long sessions scheduled over ten weeks. This treatment involves stress management, problem-solving, and learning strategies for coping with negative emotions.

To be eligible for the study participants must

• be 16 years of age or older
• have Tourette Syndrome or Chronic Tic Disorder
• be medication free or on a stable dose of medication

All adults or adolescents and their parents who are involved in the study will be asked to fill out rating scales, questionnaires, and answer questions about symptoms and behavior relevant to this project. CBIT and PST are free. Subjects will be offered $25 for each assessment visit, and compensated for parking costs on therapy visits. Participation in this study is voluntary and will not affect any future treatment in the Yale Child Study Center.

If you are interested in the project, please contact Dr. Denis Sukhodolsky at (203) 785-6446 or Joseph McGuire at (203) 785-5805.

Transcranial Magnetic Stimulation for Adults with Severe TS

TS is a chronic, waxing and waning disorder that (in a very small percentage of cases) can be associated with significant impairment and disability. Although clinical care has improved over the past decade, many individuals fail to respond to the available medication treatments or experience intolerable side effects. Most of the widely used medical interventions result in at best a 30 to 40% reduction in tic severity. The behavioral treatments such as CBIT can also be of great benefit for some individuals. For those individuals whose symptoms are severe we continue to look for new treatments. Many of you have heard about the neurosurgical treatments for individuals with very severe treatment unresponsive tics. Now we are trying another treatment that is much less costly and invasive. It is called Transcranial magnetic stimulation or “TMS.”

TMS has been used to investigate TS for the past decade and repetitive TMS (rTMS) has been used as an investigational treatment for severe TS for at least the last five years. This is not a surgical procedure. It is a technique that utilizes an electromagnet placed on the head that generates magnetic field pulses roughly the strength of an MRI scan. The magnetic pulses pass readily through the skull and stimulate the underlying brain tissue. Low frequency (once per second) TMS has been shown to induce sustained regulation of brain activity in multiple studies. Although this procedure is safe, the initial rTMS studies have had limited or no success in treating adults with severe TS. However, a recent study from Italy that targeted a brain region known as the “supplementary motor area” (known to be involved in the initiation of movement and speech) did show positive effects in five patients. Indeed, two of these patients experienced a complete remission of their tic symptoms. These improvements were maintained for three months. This was an “open” study in which patients were treated five days a week for two weeks, for a total of 10 treatments. No major side effects were noted during the course of treatment or the subsequent three months.

Working with other investigators at Columbia University (Sarah H. Lisanby, M.D., and Antonio Mantovani, M.D.) and New York University (Rodolfo R. Llinas, M.D., Ph.D., and Kerry Walton, Ph.D.), we now plan to do a double blind study rigorously test the value of rTMS for adults with severe TS. We anticipate screening 25 patients and selecting 16 patients to participate in a randomized clinical trial (8 randomized to sham and 8 to active rTMS). We will monitor the benefits of this intervention using a blind, independent evaluator (Heidi Grantz). “Sham treatment” is like a “placebo” treatment. It feels the same, but does not have the same effect.

So far two patients that we have been following have received this treatment. However, based on our experience so far, some patients may need periodic booster sessions in order to sustain their clinical improvement. If it works for adults with severe symptoms, we will likely eventually work with the Food and Drug Administration to get permission to try rTMS in adolescents with severe TS.

The treatment will be free of charge as we have just received a small grant from the Tourette Syndrome Association to support this work. In addition the Rembrandt Foundation in Philadelphia has given us the funds needed to purchase a rTMS device that we will use at the Child Study Center.

To be eligible for the study participants must

• be 18 years of age or older
• have severe Tourette Syndrome
• be medication free or on a stable dose of medication

Let us know if you or someone you know would be interested in learning more about this experimental treatment (call Heidi Grantz at: 203-737-5814 or e-mail her at heidi.grantz@yale.edu.

Neurobiological Mechanisms

We are studying the neurobiology of Tourette syndrome by direct anatomical and cellular studies of postmortem human brain samples donated by individuals with Tourette syndrome, as compared with normal control brains. These studies are ongoing in the Child Study Center’s Developmental Neurobiology Laboratory (PI, Flora Vaccarino) in collaboration with the clinical team (PI, James Leckman).

We are also currently conducting a study is to evaluate the neurobiological mechanisms of behavior therapy for tic reduction by collecting EEG data before and after therapy in children ages 8 to 12 years of age with Tourette Syndrome. Behavior therapy for tics, also known as Habit Reversal Training (HRT) consists of eight sessions administered over a ten week period. HRT, which consists of awareness training and competing response training, is designed to break the pattern maintaining tic expression. Awareness training involves describing the tic and the sensations and behaviors that precede the tic. Competing response training involves performing a behavior that is physically incompatible with the tic or makes the tic difficult to occur. As part of this study, we will record electrical signals which are produced by the brain using electroencephalography (EEG). The EEG will be recorded while children are performing simple computer tasks (such as figuring out the directions of arrows), resting, and suppressing tics. We will also collect parent ratings and clinical evaluations of tic and other conditions such as ADHD which may co-occur with Tourette Syndrome. This study is supported by the pilot/feasibility study award to Denis Sukhodolsky, Ph.D. from the Center for Self and Family Management of Vulnerable Populations at the Yale School of Nursing. Please contact Dr. Sukhodolsky at (203) 785-4664 or denis.sukhodolsky@yale.edu if you would like to receive more information about this study.