Winston-Salem Journal - Winston-Salem,NC,USA
For nearly a century, scientists made a clear distinction between schizophrenics, who have delusions, and patients with bipolar disorder, who are tossed ... http://www.journalnow.com/servlet/Satellite?pagename=WSJ%2FMGArticle%2FWSJ_BasicArti cle&c=MGArticle&cid=1031779783840&path=!living&s=1037645509005
Two mental diseases appear to be linked
By William Hathaway
THE HARTFORD COURANT
Tuesday, December 21, 2004
For nearly a century, scientists made a clear distinction between schizophrenics, who have delusions, and patients with bipolar disorder, who are tossed between episodes of mania and depression.
But researchers in the past few years have found a number of genetic and molecular common denominators. Those insights may one day help scientists track down underlying causes of two of the most devastating forms of mental illness and give drug companies new targets for therapies, scientists say.
"If we understand the common biology behind two disparate illnesses, then it will help explain why some people get one form and not the other," said Dr. Godfrey Pearlson, a professor of psychiatry at Yale University and the director of the Olin Neuropsychiatry Research Center at the Institute of Living in Hartford, Conn. "New treatments will be based on a sound knowledge of the diseases."
In the early 20th century, Emil Kraepelin, often described as the father of modern psychiatry, categorized schizophrenia and bipolar disorder as separate diseases. That view has survived in academic textbooks to this day.
Psychiatrists, however, have long noted an overlap of symptoms. Some schizophrenics exhibit symptoms of mood disorders, and some people with manic depression experience psychotic episodes. Today, some patients with bipolar disorder are given anti-psychotic drugs, and some with schizophrenia get drugs designed to treat manic depression.
But until the last decade, few scientific studies showed a biological link between the diseases.
One of those links is being explored by Amy Arnsten, a neurobiologist at Yale University Medical School, who says she has found a molecular trigger for both diseases, a trigger that seems to be activated by stress.
Bipolar patients and schizophrenics both have elevated activity of an enzyme called protein kinase C, or PKC, in the prefrontal cortex, a highly developed area of the brain that helps govern behavior and emotions. High PKC activity leads to dysfunction of the prefrontal cortex, which in turn leads to such symptoms as distractibility, impulsivity, poor judgment and possibly even hallucinations - symptoms found in varying degrees among those suffering from schizophrenia and bipolar disease. Drugs used to treat bipolar disease and schizophrenia both lower PKC activity, another sign of PKC's importance, Arnsten said.
Arnsten has found that high levels of stress tend to elevate PKC levels, which may explain why stressful events tend to trigger the onset of both diseases. She also speculates that because lead also increases PKC activity, the elevated levels of PKC may account for the distractibility and poor impulse control often seen in cases of lead poisoning.
Blocking PKC may protect the prefrontal cortex from damage caused by stress and could be useful in treating both schizophrenia and bipolar disease, she said.
Most scientists believe severe mental illness is the result of a complex interaction between environment and many genes, but finding genetic causes of mental illness has been a slow process. But the evidence is growing that schizophrenia and bipolar disease share at least a few genetic roots, said Dr. James Potash, an assistant professor of psychiatry at Johns Hopkins University Medical School.
For instance, genes suspected of playing a role in both ailments have been traced to the same region of chromosome 13, he said. Imaging studies also have shown clear differences in brain activity between patients with bipolar disease who experience psychotic episodes and bipolar patients who do not, Pearlson said.
I have a BP1 diagnosis, my brother has a more amorphous BP/schizoaffective diagnosis. Ancestors on my mothers side of the family have a clear history of mental illness that has defied categorization (partly because of the social and medical constraints back in their time).
Doesn't surprise me at all that they are more linked than was thought. I was misdiagnosed as schizophrenic after my first manic episode because the symptoms, once I actually went crazy, were very similar (the lead up was clearly mania but the hospital only saw me when I was nuts). I was on drugs for schizophrenia for more than a year and only got better once I was switched to Lithium.
My brother and I are also both gay which is interesting in this context.