Friday, September 10, 2010

The Latest in Schizophrenia Treatment

Published in the National Alliance for Mental Illness

The Latest in Schizophrenia Treatmentby Don Goff, MD

The quest to develop better treatments for people with schizophrenia is at a crossroads: Decades of research guided by stunning technological breakthroughs in brain imaging and neurobiology have produced only modest advances in the drug treatment of schizophrenia. Why have these new drugs failed despite extensive basic research?

One explanation is that schizophrenia may be far too compacted a collection of neurotransmitter abnormalities to respond to a single molecule. The rapidly progressing field of pharmacogenetics promises to identify selective drugs or nutritional interventions to match an individual's specific biochemistry - what is know as "personalized medicine." There are many examples currently under study, including the COMT gene that regulates dopamine in the area of the brain responsible for attention and short-term memory, and the MTHFR gene, which has been found to contribute to negative symptoms and cognition by regulating folate metabolism.

It is also possible that aspects of schizophrenia currently unresponsive to medication may represent errors in brain development. It would be surprising if a single drug can reverse what may be a more fundamental problem with the "wiring" underlying complex brain functions: Traditional drug treatments might only be expected to produce compensatory changes with modest benefit. How do we approach this potential problem?

Increasingly, research focuses on prevention through early detection. the NIMH-funded DECIFER study is looking at whether evaluating brain-derived neurotrophic factor (BDNF) by preventive treatment with an antidepressant can reduce early brain volume loss and improve the course of the illness. Similarly, in an intriguing preliminary study, omega fatty acids (fish oil) appeared to prevent the progression from a state of high risk (prodome) to psychosis.

The enhancement of the brain's own capacity for repair and recovery by protecting existing neurons (neuroprotection), improving their efficiency (neuroplasticity) or even by increasing the production of new neurons (neurogenesis) is another new development. Cognitive remediation, which involves computerized exercises designed to stimulate neuroplasticity, often in combination with social training or supported employment programs, has improved cognitive and social functioning and increased brain volume in early studies.

Finally, the two NIMH-funded RAISE project will examine optimal drug and psychosocial interventions in first-episode schizophrenia to determine whether existing treatments can have long-term impact. Ideally, in the not-too-distant future, new treatments based on personalized medicine and the enhancement of neuroplasticity can be combined with the best of existing psychosocial treatments to promote recovery and substantially improve the lives of people with this illness.

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