Bipolar Plus Panic May Be Distinct Disorder, Study Finds

In a sense, life for bipolar patients can be an emotional roller-coaster ride, with exhilarating, but potentially dangerous highs, and devastating, potentially dangerous lows. And if that ride weren’t taxing enough, a third of bipolar patients are also estimated to suffer from panic attacks.

This double disorder, so to speak, may be genetically distinct from bipolar disorder alone.

So suggest the results of a study conducted by Alessandro Rotondo, M.D., a molecular geneticist and assistant professor of psychiatry at the University of Pisa in Italy, and his colleagues. They report their results in the January American Journal of Psychiatry.

There is a gene located on chromosome 22 called the COMT (catechol O-methyltransferase) gene that makes an enzyme that breaks down the nerve transmitters dopamine, norepinephrine, and epinephrine. What’s more, a particular variant of this gene has been linked with bipolar disorder. So Rotondo and his team decided to use this gene variant to see whether they could show that bipolar disorder without panic is genetically distinct from bipolar with panic.

They took DNA samples from 127 subjects without psychiatric illness, 49 bipolar subjects with panic disorder, and 62 bipolar subjects without panic disorder. They then examined each DNA sample to see whether it contained one copy of the gene variant of interest—that is, whether a particular subject had inherited one copy of the variant from one parent. They then calculated the percentage of subjects in each of the three groups who possessed one copy of the gene variant.

Only 39 percent of the control subjects had one copy of the variant, the researchers found. In contrast, 48 percent of bipolar subjects with panic disorder had it. This 48 percent was somewhat more than the 39 percent of controls, but not significantly different from it. However, 56 percent of bipolar subjects without panic possessed a copy of the variant. The 56 percent was a highly significant difference from the 39 percent of controls.

The researchers then examined DNA samples from their subjects to see whether any samples contained two copies of the gene variant—in other words, evidence that subjects had inherited a copy of the variant from each parent.They then calculated what percentage of subjects in each of the three groups possessed two copies of the gene variant.

Whereas only 15 percent of controls had two copies of the gene variant, 22 percent of bipolar subjects with panic had it, the researchers found. This 22 percent was somewhat more than the 15 percent of controls, but not significantly different from it. However, 40 percent of bipolar subjects without panic had two copies of the gene variant, the researchers discovered. This 40 percent was a highly significant difference from the 15 percent of controls who had it.

Evidence Builds

These findings thus support previous evidence that the COMT gene variant plays a role in bipolar disorder. But they also suggest that the variant is only a culprit in bipolar disorder per se, not in bipolar plus panic disorder. This points to the likelihood that bipolar disorder without panic is genetically distinct from bipolar with it, as Rotondo and his colleagues suspected.

But the researchers did not stop there. They decided to see whether they could bolster their case that bipolar without panic is not genetically identical to bipolar with panic. To evaluate this they decided to use another rogue gene variant that had previously been associated with bipolar disorder as their exploratory tool. It came from a gene called the 5-HTT gene. This gene is located on chromosome 17 and is involved in the transport of the nerve transmitter serotonin.

Rotondo and his colleagues examined DNA samples from each of their subjects to see whether any contained one copy of the maverick gene. They then determined what percentage of healthy subjects, what percentage of bipolar-with-panic subjects, and what percentage of bipolar-without-panic subjects had one copy of the gene variant and compared the percentages for the three groups.

Highly Significant Difference

Compared with the 43 percent of controls who had at least one copy of the gene variant, 49 percent of bipolar-with-panic subjects did, the researchers found, a percentage that was not significantly different from the percentage found for controls. However, 58 percent of bipolar-without-panic subjects had at least one copy of the gene variant, they discovered. This 58 percent was a highly significant difference from the 43 percent of controls.

Finally, the investigators examined DNA samples from each of their subjects to see whether any contained two copies of the rogue gene—in other words, evidence that a subject had inherited a copy of the maverick gene from each parent. The researchers then determined what percentage of healthy subjects, what percentage of bipolar-with-panic subjects, and what percentage of bipolar-without-panic subjects had two copies of the gene variant and compared the percentages for the three groups.

Whereas only 19 percent of controls contained two copies of the gene variant, 20 percent of subjects with bipolar plus panic did. The 20 percent was not significantly different from the 19 percent of controls. But 32 percent of bipolar-without-panic subjects contained two copies of the gene variant, the scientists discovered. The 32 percent differed significantly from the 19 percent of controls.

These findings thus shore up previous evidence that the 5-HTT gene variant plays some role in bipolar disorder. But they also suggest that the variant is only implicated in pure bipolar, not in bipolar plus panic.

Indeed, when taken all together, “these results suggest that bipolar disorder with and without comorbid panic disorder represent distinct genetic forms of this mood disorder,” Charles Nemeroff, M.D., chair of psychiatry at Emory University School of Medicine, writes in an editorial accompanying the study report.

In fact, if bipolar without panic is genetically distinct from bipolar with it, it raises some “fascinating questions,” Nemeroff pointed out. For example, he asked, “Do these two groups differ in course of illness, vulnerability to comorbid medical disorders such as coronary artery disease, and treatment response?”

Nemeroff’s comments prompted Psychiatric News to ask Rotondo whether he and his colleagues will now be trying to answer some of these questions. The answer was yes. “There is already evidence from several studies that panic disorder and high-anxiety levels in the context of bipolar disorder predict greater severity, poorer prognosis, and resistance to pharmacological treatments,” Rotondo explained. “Therefore, we will be working not just on replicating our initial findings on a larger sample, but on trying to understand the impact of panic disorder on the outcome and treatment response of bipolar disorder patients.”

The study was financed in part by the Institute for the Treatment and Prevention of Depression and Anxiety in Milan, Italy.

The study report, “Catechol O-Methyltransferase, Serotonin Transporter, and Tryptophan Hydroxylase Gene Polymorphisms in Bipolar Disorder Patients With and Without Comorbid Panic Disorder,” is posted on the journal’s Web site at http:ajp.psychiatryonline.org under the January issue. ▪

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