Winter 2004 Volume 16, Number 2	A Special Kind of Bipolar Cues lie in the common ground with schizophrenia.
	The idea that schizophrenia and bipolar disorder stand as two distinct trees in the forest of mental illness came from German psychiatrist Emil Kraepelin in the late 1800s. So began the separation of the diseases that still marks today's psychiatry. "Yet, in practice," says psychiatrist James Potash, M.D., "it's not always easy to distinguish the two disorders."

Bipolar patients can experience schizophrenia-like hallucinations and delusions in a rather chronic form of the illness, says Potash. Psychosis touches bipolar I disorder - the severe form - in as many as 58 percent of patients, though type and degree may vary. "Likewise," he says, "we see schizophrenic patients with major depression or even manic episodes." The trees' roots overlap. But rather than treat the overlap as a diagnostic annoyance or tuck it away in the drawer marked schizoaffective disorder, Potash and colleagues are strengthening beliefs that psychotic bipolar disorder may have its own genetic story and distinct biology. To that end, Potash's team is hunting genes. "If we knew genes associated with psychotic symptoms," he says, "we'd have an anchor, a point to investigate their action in the brain." That's not to mention other benefits that could follow-surer diagnosis, more finely tailored therapy for bipolar patients and a window into schizophrenia. As a first step, Potash has shown that psychotic bipolar illness runs in families. Recently, his team analyzed the families of 65 bipolar patients-part of a broader, major bipolar study under J. Raymond DePaulo Jr., M.D. Interviews and resulting pedigrees bore out the family tie: If one family member has bipolar disorder I with psychotic symptoms, Potash says, other bipolar members of the family are three times likelier to have them too. Now the team's refining the search. For some time, Potash had followed so-called linkage studies at Hopkins and elsewhere. That work links certain variable patterns in segments of DNA-markers-to patients with a disease. Such studies have found DNA "hot spots" linked with bipolar disease on seven different chromosomes. Schizophrenia, too, has areas believed most likely to hold risk-making genes. But news that both diseases share some chromosomal hot spots put Potash on alert. He reasoned that symptoms common to both diseases could spring from common genes. Taking DNA samples from patients and focusing on four of the shared areas, he showed that's apparently true: The more psychosis in a bipolar family, the more likely members are to have "suspect" DNA in areas common to the two diseases, specifically on chromosomes 13 and 22. In short, susceptibility genes for psychosis-tinged bipolar disorder may lie there. But the actual genes remain elusive. So the team's employing a newer technique, SNP genotyping, that, because it follows smaller shifts in DNA, can narrow the search. "Already," says an enthusiastic Potash, "we're on the trail of a group of genes that appear turned on both in schizophrenia and in bipolar psychosis." For more information, call 410-614-1017.