Early Detection and Prevention of Schizophrenia

The Sunday morning session at the NAMI 2008 convention featured two psychiatrists working on the cutting-edge of research and treatment for schizophrenia: Ed Scolnick, M.D., director, Psychiatry Initiative, the Broad Institute, Cambridge, MA and William Cook, Ph.D., director, Psychiatry Research, Maine Medical Center, Portland, ME.  First, I'll report on the information presented about research, and then look at the promising results of an early intervention program.

Scolnick offered this hope: "We're in a different era for the first time ever understanding complex human genetic diseases."  Medicines in development are based on neuroscience research.  The single largest risk for schizophrenia is the sequence of letters in genes.  Identical twin studies indicate if one person has schizophrenia, the other has a 50 to 80 percent chance of getting it.  Indeed, your risk goes up tenfold if someone genetically related to you has the illness.

The goal is to find all the genes for schizophrenia.  New approaches to finding a schizophrenia gene include whole-genome association studies.  The biological implications being evaluated will be clues to underlying causal pathways.  For the first time in the history of the field there is a way forward that can lead to significant improvements in diagnosis and treatment.

Since 2003, when the human genome was first mapped, researchers have been tracking the patterns of genes and gene interactions to unlock the complex condition that is schizophrenia.  This task may also offer genomic information to aid in treatment tailored to the individual.  Possible new drugs include these kinds of agents:

• Glu 2,3 agonist
• D-cycloserine
• N-desmethylclozapine
• M1 allosteric agonists
• Gaba alpha 2,3 agonist
• PDE-10 inhibitors
• Alpha-7 nicotinic agonists

This brings hope, as N-desmethylclozapine, the Gaba alpha and Alpha-7 are all agents believed to work on cognitive deficits.  D-cycloserine is a novel regimen used with psychotherapy.  The ultimate goal is to teach patients new behaviors and paradigms to increase the rate at which they learn to cope so medication isn't life-long.  It has proven helpful in acrophobia (fear of heights) and anxiety.  The difference is it is not a dopamine or serotonin agent. 

The truth is I wouldn't want to take a drug unless I absolutely had to, and I'm sure you would feel that way, too.  The sentiment is that in five to 10 years the research will lead to a much greater molecular understanding.  In one study, there was an excess of DNA deletions in genes in samples of patients versus controls.  Larger samples are needed to detail where the deletions are.  However, this discovery won't make treatment harder; it's an optimistic finding.  For the first time, new methods in genetic research are rapidly developing more detailed maps.  While it's too early to expect a cure or a vaccine, this news dovetails with the words of Stephen M. Goldfinger, M.D., who I interviewed and who spoke about the benefits of new drugs as early as three years away.