Treating Schizophrenia by Correcting Abnormal Brain Development

Addition of Tiagabine to Second-Generation Antipsychotics in the Treatment of Recent-Onset Schizophrenia by Modification of Developmental Reorganization of the Prefrontal Cortex

The purpose of this study is to determine whether treatment with tiagabine (Gabitril) during the early course of schizophrenia can fundamentally correct the brain deficits associated with the disease. This study is funded by the National Institutes of Health.

It is hypothesized that enhancement of GABA neurotransmission during the early course of the illness by tiagabine (Gabitril), a GABA transporter GAT-1-specific inhibitor and a FDA-approved anticonvulsant, will improve both clinical symptoms and working memory in schizophrenia. This improvement is postulated to be the result of tiagabine-mediated modification of the developmental synaptic pruning of prefrontal cortical circuitry. The occurrence of circuitry modification after tiagabine treatment will be assessed by the following independent methodologic approaches: MRI morphometric analysis of prefrontal gray matter volume and fMRI measurements of brain activity patterns during performance of tasks that probe working memory.

Half of the subjects will receive the study medications in addition to their ongoing antipsychotic regimen.

Working memory will be assessed at baseline and at 6-month time point to see if working memory changes after 6 months compared to baseline measurement

Executive function, which is a complex form of working memory, will be assessed using the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) battery

Executive function will be assessed at baseline and at 6-month time point to see if executive function changes after 6 months compared to baseline measure

Symptoms will be assessed at baseline and at 6-month time point to see if symptoms change after 6 months compared to baseline measures

Inclusion Criteria: Meets criteria for the diagnosis of schizophrenia, with onset of psychotic symptoms within the past 3 years. Currently on second-generation antipsychotics for at least 3 months. Age 18-25, otherwise healthy. Exclusion Criteria: Diagnosis of schizoaffective disorder. Has failed two or more clinically adequate antipsychotic trials. History of seizures or any neurologic disorders. Pregnant or nursing women. Known HIV infection. Actively suicidal. History of any substance dependence. Currently meets criteria for substance abuse/dependence. Other MRI exclusion criteria per Radiology Department protocols.

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