AUG 20, 2014 12:00 AM PDT

Americans and schizophrenia

WRITTEN BY: Peter Micheli
Only about 1% of Americans have schizophrenia, but the agitation, hearing of voices, and paranoia it causes can lead to devastating and deadly outcomes. It has long been observed that schizophrenia can be inherited, indicating that genes are involved in its development. A recent study, the results of which have been published in Nature, has made a link between the disease and specific genes. The researchers looked at genomewide data from 36,896 cases and 113,075 controls, identifying 108 genes associated with schizophrenia. Some of the genes identified, such as those linked to regulating the brain chemical dopamine, were not a surprise. Others such as those associated with the immune system and heavy smoking, were not anticipated. "Some are very familiar genes expressed in nerve cells, and some are results where you scratch your head and know you have more work to do," said Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, a leader of the study.

Smaller studies have suggested a connection between the immune system and schizophrenia. Schizophrenics often show signs of inflammation in their bloodstream and people related to those with autoimmune disorders have up to a 45% greater risk of developing schizophrenia. This study confirms the link. It's not so clear why genes associated with smoking are involved with schizophrenia. Because the study is so large (the largest molecular genetic study of any neuropsychiatric disorder) it's fairly certain that any gene identified in the study plays a significant role in schizophrenia, but not every gene linked to the disease has been identified yet. Hyman says, "Now we have 108 pieces, but maybe it's a 1,000-piece puzzle, so we have a long way to go.

Drugs are available to treat schizophrenia, but they do not work well for many patients. All current drugs work through blockade of the type 2 dopaminergic receptor, but since the discovery of this mechanism over 60 years ago no new effective antipsychotic drug has been developed that takes a different approach.

In a column in Nature discussing this research, David Adam compares the current understanding of psychiatric disorders to the knowledge of cancer about a decade ago, before molecular approaches could target patients for treatments specific to them. He writes, "The latest study on schizophrenia could be a small step forward in this march. Or it could be another false start in a field that has endured more than its fair share. Psychiatric research has yet to provide a single reliable biomarker to aid diagnosis and treatment. Self-reported symptoms and their subjective interpretations remain the basis for clinical diagnosis. Drug companies have walked away. The task of unraveling the biological pathways that drive mental illness, which are needed before drug targets can be identified, has been declared too difficult and expensive." He goes on to say, despite this, the understanding of mental illness has made relatively rapid progress, that just a generation or two ago, a common treatment for schizophrenia "was a metal spike hammered through the top of the eye socket and waggled around." It is hoped that this study, by identifying causes of schizophrenia, will help lead to much needed new treatments for the disease.

Adam feels that this new knowledge about the causes of schizophrenia will help those who suffer from other forms of mental illness as well. Schizophrenia is not made light of as some other conditions such as depression and obsessive compulsive disorder (from which Adam suffers) often are. By proving that schizophrenia has biological roots, it is hoped that patients with other conditions will be given the respect and treatments they need, too.
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