Researchers in the Schizophrenia Focus Group study the manifestations, causes and innovative treatments for schizophrenia, a serious, chronic and debilitating neuropsychiatric disorder that affects approximately one percent of the world's population. Available medications treat only the positive symptom complex of this diverse, multigenic disorder frequently leaving the cognitive, affective and social impairments of the disease unaffected. There appear to be three primary challenges for the future in schizophrenia research that are being actively pursued by focus group members. The first challenge is to identify the molecular and/or genetic defect that plays a central role in the ontogeny of the disease. A second major challenge will be the integration of the new molecular/genetic information into developing new treatments for schizophrenia that will replace the antiquated antipsychotic medications currently being used to alleviate schizophrenic symptoms. The final challenge for investigators will be to translate the molecular/genetic defect identified as the main pathophysiological cause of the disease into a functional context to gain a better understanding of how the symptoms of the disease of schizophrenia develop. This final set of investigations will have great need for new animal models of the disease and the ability to move this information from the bench to the clinical arena expediently.
Schizophrenia is a clinical syndrome that comprises several separate disease entities. It involves multiple genes interacting with environmental insults to form a brain vulnerable to the illness. The illness usually has subtle manifestations during development and more remarkable symptom manifestations during early adulthood. Schizophrenic patients experience reality distortion, disorganization of thought, and negative symptoms. Additionally, patients exhibit impairments in cognition with extraordinary difficulties processing new information, especially visual-spatial information.
Investigations by researchers within the Schizophrenia Focus Group address many aspects of the disease. Due to the unknown origins of the disease, preclinical investigators are exploring potential developmental mechanisms that could contribute to the pathophysiology of the disease. The advent of new molecular approaches to modify gene expression in developing brain tissue, as well as the adult brain, may provide important new targets for developing pharmacological agents for schizophrenia. New molecular targets may also be identified by analyses of post-mortem schizophrenic brain tissue at both the proteomic and genomic levels.
For many years, dopaminergic mechanisms were thought to play a pivotal role in schizophrenia, however, compelling evidence to support the integral participation of dopamine has been slow in coming. As such, other targets like glutamate have become central foci for investigations. Studies in both preclinical and clinical arenas are exploring glutamate receptor alterations in schizophrenia and responsiveness of patients to glutamatergic agents. Nicotine now figures prominently in focus group research activities since virtually all schizophrenic patients use tobacco products. Unfortunately, the beneficial effects of nicotine are only tangentially known. Studies are underway by members of the focus group to elucidate the effects of nicotine in information processing paradigms of both normal subjects and patients with schizophrenia as well as experimental animals.
Antipsychotic medications are effective in the treatment of the psychotic symptoms of schizophrenia, like delusions and hallucinations, but they are highly ineffective in treating the cognitive impairments many schizophrenic patients have, as well as the negative symptoms of the disease. Clinical investigators in the Schizophrenia Focus Group are actively involved in trials of new medications for treating the cognitive and social impairments of the disease. Our ability to look inside the behaving human brain using imaging techniques has revolutionized the study of neuropsychiatric disorders. Through the use of these sophisticated neuroimaging techniques, new information about normal cognitive processes is being generated by focus group investigators. Moreover, by combining neuroimaging techniques with neuropsychological testing, glimpses of differences between normal human subjects and patients with schizophrenia are beginning to emerge. An additional mechanism to profile brain functioning is through the use of electrophysiological techniques. Interestingly, virtually the same electrophysiological evaluation that is performed in patients can be performed in experimental animals. Schizophrenia Focus Group studies show that brain function in schizophrenic patients differs from normal control function. Clinical investigations are underway to determine whether antipsychotic medications or other antischizophrenic compounds are useful in normalizing the electophysiological abnormality of schizophrenics. Parallel studies in experimental animals demonstrate the importance of several neurochemicals, like nicotine, in normalizing responses in patients. The ability to perform bench to bedside analyses is a hallmark of the interdisciplinary approach being taken by Schizophrenia Focus Group members to gain a better understanding of the pathophysiology of schizophrenia.