Dr. Fischbach opened by noting that he would be addressing three major groups in 2002−the American Psychiatric Association, the American Neurological Association, and the American Neurosurgical Association−and that this breadth of audience reflects the growing understanding within different medical specialties that much of the basic science underlying different clinical developments is the same.

He noted that Sigmund Freud moved from electrophysiologic work to psychological conceptualization because he needed to seat his results within a theory of mental life. In contrast, current scientists will use improved understanding of psychopathology and psychopharmacology to revolutionize theories of cognitive understanding and mental life.

Dr. Fischbach laid the groundwork for the remainder of his talk in a discussion of the diversity of known neurodegenerations (see Table), all of which at some level raise the question of how to activate and deactivate apoptotic neuronal loss.

　

A sampling of neurodegenerations at different stages of life. ・ Disorders of the aging brain: Alzheimer's disease, Parkinson's disease ・ Disorders of younger adults: Huntington's disease, amyotrophic lateral sclerosis, prion diseases ・ Disorders of children: spinocerebellar ataxia, Tay-Sachs disease and other storage diseases

He laid out a general framework that may apply to many of these seemingly diverse conditions:

Dr. Fischbach noted that the mass loss with schizophrenia can be quite large, in the magnitude of 2-3% loss per year, especially in the dorsoparietal cortex. With this knowledge, he believes researchers can find clues to the region of the brain within which the disordered thought of schizophrenia begins (the dorsoparietal cortex). When region can be confirmed, studies to arrest or reverse neuronal loss in the target region may begin.

This transition from understanding of key areas to work in arresting or reversing neurodegeneration has already occurred with Parkinson's disease, where he noted the success of pilot studies that targeted regions within the subthalamic nucleus for deep-brain stimulation.

In one case, functional magnetic resonance during electrode placement allowed researchers to place an electrode so precisely that the patient's contralateral motor symptoms were extinguished. Initial results from some studies suggest that long-term stimulation may even have trophic effects.

In summary, he believes it likely that much of the current functional and imaging work done with psychiatric conditions will reveal key locations of neuronal dysfunction and loss. Once target locations are established, further work may reveal the mechanisms through which loss occurs and the means through which loss can be arrested or reversed.

He closed with an observation drawn from work with Parkinson's disease: When the earliest clinical signs are seen, roughly 75% of neurons in the target region have already been lost. Thus, early diagnosis of individuals at risk for disease or presenting with early-stage disease is critical to improved care and better prognosis.

(abstract Lecture 4)