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 Centre for Addictionand Mental Health |
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Research
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Schizophrenia: Research Annual Report 2003Section Head: Dr. Shitij Kapur The Schizophrenia Research Program is dedicated to understanding the causes and mechanisms of recovery of schizophrenia, with the hope of improving the lives of people and families affected by the illness. In pursuit of this goal, our methods range from molecular studies to community-based research. Genes and Schizophrenia: Animal Models of Schizophrenia Dr. Albert Wong and colleagues are using animal models to identify candidate genes for schizophrenia. The team has discovered that two genes, 14-3-3 eta and syntaxin1a, are associated with schizophrenia (Molecular Psychiatry, 2003). Now, we ask the question of how these genes lead to schizophrenia; studies are under way to test how these genes affect the release of brain chemicals and are involved in brain development. Genetic Subtypes of Schizophrenia Drs. Anne Bassett and Eva Chow lead the Clinical Genetics Research Program team, focusing their research on genetic subtypes of schizophrenia. Drs. Bassett and Chow have been instrumental in showing that 22qDS (deletion syndrome of 22q) represents an identifiable genetic subtype of schizophrenia. With support from the W. Garfield Weston Foundation, our team is following over 70 adults with 22qDS to determine the developmental, psychiatric and medical features, as well as the molecular genetic make-up, of this complex subtype. We have also started a study of children and adolescents with 22qDS, who have a high risk of developing schizophrenia. (Supported by NARSAD and Bill Jeffries Schizophrenia Endowment Fund). Dr. Chow reported in 2002 (Biological Psychiatry 51: 208-215m 2002) that brain structure in 22qDS-schizophrenia resembles that of other forms of schizophrenia; this is leading us to study whether brain structural features may predict who will develop schizophrenia in young people with 22qDS. Tackling Schizophrenia Before It Begins Drs. Robert Zipursky, Irvin Epstein and colleagues have been leading the Prevention through Risk Identification, Management & Education (PRIME) research clinic in early detection strategies and treatment, using psychological tests and brain imaging. These approaches are already showing promise (Biological Psychiatry, Woods et al, 2003). Recently, the team of Drs. Jean Addington, Zipursky, Epstein and colleagues has begun a five-year project, in collaboration with the Universities of North Carolina and Yale, to improve early identification of people who are likely to develop schizophrenia. Early and accurate identification of risk for schizophrenic psychosis may be the field's best hope for developing more effective treatment strategies, including secondary prevention of this typically devastating disorder. (Funded by NIMH). Drugs and Therapy Go Hand-in-Hand For many years, we have known that antipsychotic drugs work on the dopamine neurotransmitter. However, we do not understand how drug action on this neurotransmitter takes away the delusions and hallucinations that are a symptom of psychosis. Dr. Shitij Kapur and colleagues have proposed a new theory to link dopamine to psychosis and to antipsychotic treatment (American Journal of Psychiatry, 2003). According to this theory, drugs provide a background of dampened salience of symptoms; this background makes it easier for the person to give up his or her delusions and hallucinations. Our theory predicts how drugs and therapy may actually work hand in hand. Studies are now under way to test this new theory. Cognitive Behavioural Treatments: A Focus on Functional Recovery While antipsychotic treatment takes away symptoms of schizophrenia, not everyone returns to their original level of functioning. Recently, the field of schizophrenia research and treatment has not focused on individual psychotherapies, but the last few years have seen a growing interest in this area. Dr. Jean Addington, a leader in psychological interventions for psychosis, is currently leading the development of new types of psychotherapies for people who are in the early stages of schizophrenia, and is examining if these therapies lead to improvement in functional outcome (funded by the NIH, USA). Understanding and Managing Side-Effects Drugs have side-effects. This cannot be avoided. In the Schizophrenia Research Program, we strive to understand antipsychotic side-effects, to help people manage them. Dr. Tony Cohn, in association with Dr. Gary Remington, runs a research-treatment clinic focusing on weight gain and diabetes
problems for people taking antipsychotics. This clinic has led to several new discoveries. In people who have experienced chronic psychosis over many years, we found a two- to three-fold increase in rates of type 2 diabetes, abdominal obesity and a syndrome of insulin resistance and abnormalities in cholesterol and glucose metabolism, both in hospitalized and community patients with schizophrenia. (Presented by Dr. Cohn at the International Congress on Schizophrenia Research, 2003). These factors, combined with the very high rates of cigarette smoking (70 to 80 per cent) in this population, suggest a markedly increased risk for coronary heart disease. In screening for diabetes among this same group of people with chronic psychosis, we have found that the recommended fasting glucose procedure is only 20 per cent reliable in detecting undiagnosed diabetes and five per cent reliable for determining if persons are at risk for diabetes, compared with a different screen test, the glucose challenge. This has led us to develop new guidelines for testing for diabetes and risk for diabetes in people with schizophrenia. Beyond Drugs and Psychotherapy: Magnetic Stimulation as a Treatment Drs. Jeff Daskalakis and Bruce Christensen have been conducting studies using a new research technique called transcranial
magnetic stimulation (TMS). Our studies have shown, for the first time, that people having an active psychotic episode of
schizophrenia show abnormal inhibition of neuronal activity of the front part of the brain (Archives of General Psychiatry,
2002). These studies show the path to possible new treatments. We are now working to see if magnetic stimulation can be used to treat these inhibition deficits and lessen hallucinations for people with schizophrenia that does not respond to conventional treatments. Neuropsychology: Exploring How the Brain Works Working in the Neuropsychology Lab, Dr. Christensen and colleagues focus on the cognitive and neurobiological effects of schizophrenia. One of the challenges in this area has been to understand the wide variety of cognitive changes associated with this illness in terms of a unified reason. We have proposed that schizophrenia-related cognitive impairment may be associated with one of two major developmental brain pathways: the pathway that controls goal-directed activity. As part of our ongoing work in this area, we have completed a study using a visual discrimination paradigm and a visually guided reach paradigm, both of which support this hypothesis -- both of these studies have been presented at international conferences and we are currently preparing manuscripts for each. We are also interested in understanding the prominent memory deficit that is associated with schizophrenia; for example, in people with schizophrenia who do not use memory strategies to improve recall, such as mentally grouping items that belong to the same category (e.g., apple, pear and banana are all fruits). In a recent study, we have shown that, although patients are able to learn category strategies, having the skill does not improve their recall. This type of problem has been termed a "utilization deficit" and may reflect how general intellectual deficits interfere with using new skills. Our findings also suggest the need for repeated practice in skills training for people with schizophrenia. |
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Last updated: Aug 24, 2004 3:24 PM Published: Oct 07, 2008 8:47 PM ID#P5724 |