Commonwealth Research Center
A Novel Test-of-Concept Approach to Treating Schizophrenia by Correcting Abnormal Brain Development
Principal Investigator
T.-U. Wilson Woo, M.D., Ph.D., Assistant Professor of Psychiatry, Harvard Medical School
Introduction
Along with our clinical research program, we actively pursue to understand the genetic and molecular mechanisms of neural circuitry disturbances in the cerebral cortex in schizophrenia. One of the goals of our program is to attempt to collectively translate findings in the laboratory into clinically meaningful practice – This may eventually lead to novel therapeutic and prevention strategies for patients suffering from this devastating illness.
Rationale
Converging lines of evidence suggest that the prefrontal cortex is functionally disturbed in schizophrenia, leading to a multitude of symptoms and deficits. In fact, recent research strongly suggests that synaptic connections within the prefrontal cortex may be abnormal in schizophrenia. During the period of late adolescence and early adulthood, when overt symptoms and deficits of schizophrenia typically begin to emerge, synaptic connections within the prefrontal cortex undergo a process of modification before they become functionally mature. Therefore, it is believed that this synaptic modification process may somehow “trigger” the onset of schizophrenia. This hypothesis implies that we may be able to fundamentally improve the course of schizophrenia, during the early phase of the illness, by modifying the synaptic modification process.
Study Design
We have designed a study to investigate this possibility. This study employs a double-blind placebo-controlled add-on design. Before enrolling in this study, patients must first be stabilized on antipsychotic medications. Once enrolled, the patient undergoes both structural and functional magnetic resonance imaging (MRI) to obtain baseline assessments of the morphology and functions of the prefrontal cortex. The patient will then be randomized to receive either the study drug tiagabine (Gabitril) or a placebo added on to the antipsychotic medications. After six months, repeated structural and functional MRI assessments will be performed to see if the study drug will in fact correct the morphological and functional disturbances of the prefrontal cortex.
Subject Participation
This study takes place at the Massachusetts Mental Health Center and the Massachusetts General Hospital. Patients who are between 18 – 25 years of age, who have been diagnosed with schizophrenia or schizoaffective disorder within the last 3 years, and who are currently taking antipsychotic medications with the exception of clozapine may be eligible to participate. Patients enrolled in this study are compensated for their participation.
If you would like further information on this study, please contact:
Fran Schopick, M.S.W.
Phone: (603) 953-3022
Email: [email protected]
For additional reading, please go to:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9560277
This study is also listed at clinicaltrials.gov:
http://clinicaltrials.gov/ct/show/NCT00179465?order=1
This study is funded by the Stanley Medical Research Institute (http://stanleyresearch.org/).