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Psychiatry Newsletter - A Psychosis Gene?

Hopkins BrainWise Fall 2008

A Psychosis Gene?

Date: October 12, 2010

Dr. Fernando Goes
This subgroup of bipolar patients with psychosis may help us pinpoint the gene, says Goes.

Mr. B, who suffered from bipolar disorder (BP) for 30 years, had unusual thoughts and behaviors, but unusual in a typical way. When, for example, he’d stopped treatment and slipped into mania, Mr. B hallucinated that a neighbor wanted to harm him. Troubled by this, he attached an aluminum foil antenna to his radio to project the neighbor’s voice and so warn his family.

Ms. C, who also had lived long with bipolar illness, had “incredible insight,” she said, during a manic period that coincided with the start of the war in Iraq. She felt certain she could bring world peace because the baby she would soon deliver would mark the second coming of Christ. *

While both patients were no strangers to psychosis, there’s a difference in the way their thinking goes amiss. In investigating that, psychiatristFernando Goes and colleagues have clarified the biology of psychosis. Also, they’ve gained insight on one form of bipolar disorder and are closer to confirm a gene for the risk of it—all steps toward better therapy. 

Mr. B has mood-incongruent psychosis, meaning, Goes explains, “that the delusions suffered apparently lack ties to the person’s abnormal mood.” Mrs. C’s mood-congruent thoughts, however, follow more reasonably from her overactive mood.

“Bipolar disorder is more complex than we’d thought,” says Goes. “We now see it as more of a syndrome covering a number of diseases. And that complexity is probably why we’ve been stumped in mapping the genes.” Today’s approach, however, uses those differences. Researchers try to isolate subgroups of BP patients marked by some characteristic: Some, for example, have the classic euphoria of mania, while others have more irritable or “mixed” mania. Only around half of bipolar patients experience psychosis. And, to narrow it further, such psychosis is mood incongruent in only a third of them.

“Narrowing bipolar disorder clinically should let us narrow it down genetically,” Goes explains.

 In studying bipolar psychosis, the Hopkins team turned to their records of hundreds of study volunteers with the disorder—coded by number and not by name—who’d given detailed personal and family histories and blood samples. As part of a government project to get a large enough group to be trustworthy, those data from 708 families were analyzed and pooled with others from nine academic centers.

The results? Patients with mood-incongruent BD have a more severe illness. They’re hospitalized, for example, or turn more often to addictive drugs. And the disorder clearly runs in families.

Even more interesting is the possibility that a gene underlies the disordered thinking—one on chromosome 13. Earlier Hopkins studies linked that site with both schizophrenia and psychotic bipolar disorder. “The fact that there’s an overlap,” Goes says, “tempts us to say there’s a psychosis gene, one that brings a distinct character to illness, one we could target in therapy.” n

 *We’ve altered both patient stories to protect identity.

 For information: 443-287-6382

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