Mentor: Carol Tamminga, M.D.
Department of Psychiatry

Human brain imaging studies of people with schizophrenia demonstrate replicable, task-specific regional cerebral blood flow (rCBF) pattern abnormalities localized to the anterior cingulate gyrus and middle frontal cortex. The abnormalities in frontal rCBF are thought to be associated with the cognitive symptoms of schizophrenia. These symptoms include defects in attention, learning, short-term memory, and executive function, and are a persistent, core feature of this illness. Traditional antipsychotics like haloperidol fail to demonstrate improvements in cognitive domains and may actually worsen cognition. Some of the newer serotonin-dopamine antagonists have shown some benefits in certain cognitive domains, but improvements have been modest. These cognitive deficits are strongly linked to functional outcomes such as social competence and the capacity for work, so there is a need for new treatments for these symptoms.

There is evidence that cognitive remediation strategies such as instruction, practice, and reinforcement can improve performance on various tests of cognitive function. Hypothetically, drug treatment could augment the remediation response. We will study the effects of atomoxetine, a relatively selective noradrenergic reuptake inhibitor that purportedly increases blood flow to critical frontal structures, so the frontal cortex can have a better chance to regain active function in the context of cognitive remediation training. In addition to various conventional neuropsychological tests, we plan to use quantitative measurement of rCBF deficits as a biological surrogate to assess the impact of our interventions.

Kenny will participate in all aspects of this study, including patient recruitment and evaluation, observation of neuropsychological testing, cognitive rehabilitation, and acquisition and interpretation of functional MRI rCBF data. There will be a special emphasis on evaluation of brain function using functional imaging approaches and cognitive measurements. In addition to this main project, he will participate in protocol design and grant writing for additional new projects in what will be a thorough introduction to the techniques of clinical research in schizophrenia.