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School of Medicine
News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences
The search for a biomarker prompts a fascinating thought: Do bipolar patients have a learning disorder?
Ten years ago, psychiatrist Dean MacKinnon crawled into a spelunker’s equivalent of a spider hole and it wasn’t a jolly experience. On a caving expedition, he’d imagined walking through caverns, seeing stalactites. But after resting in a small, tight space, he says, “I suddenly felt rather desperate to get out.” He couldn’t seem to get his breath, and confessed it, sheepishly, to the guide. “Oh, that always happens here,” was the reply. “It’s the least ventilated part of the cave.”
Now MacKinnon’s understanding of what it’s like breathing elevated CO2 and his sharpened sense of the human urge for a good breath may have paid off. “I think it planted a seed,” he says, one that, with diligence, could grow into a biomarker for bipolar disorder (BD). Because, by definition, biomarkers signal a disease cleanly—without the confounding effects, say, of violence in patients’ lives or the expertise of their diagnosing psychiatrists—they’re much in demand. So MacKinnon’s intent on his search.
And the basis for such a marker? It doesn’t hinge on a jump in cortisol or some other stress-related chemical, he explains, nor is it finding a nerve transmitter gone askew. Rather, it rests on the idea that at least part of BD comes from a disorder in emotional learning.
“The brain is primarily a learning machine,” Mac-Kinnon says. “It takes in sensory information, then puts two and two together for behavior that avoids danger and satisfies appetites.”
And it’s that so-called appetitive behavior that’s the focus here. Classic bipolar disorder, of course, brings recurring highs and bouts of depression. But manic and depressed patients also find themselves either hypersensitive or numbed to appetite’s influence on behavior: “Depressed patients have little motivation,” says MacKinnon. “They’ve little zest for activities that normally bring reward—sleep, nutrition or socializing, for example.” Conversely, someone in a manic state seems driven by intense and varied urges, to the point of being unable to manage them. All, he says, may stem from failure or inefficiency in conditioning, the most basic sort of learning.
Perhaps the chemistry within the brain’s synaptic classrooms is altered—it may be no coincidence that some candidate genes for BD retool synapses. Whatever the biochemical flaw, the changes in patients, he believes, are what you’d expect with an inability to link need, behavior and reward. “My argument,” says MacKinnon, “is that at times of stress or change, people with bipolar disorder can’t maintain that sort of learning.”
That’s where breathing comes in. MacKinnon suspects that bipolar patients’ possible difficulty in adapting breathing—an innate appetite-driven behavior—mirrors their inability to learn and regulate emotional behavior. His “aha moment” then, is using one as a marker for the other.
Recently, he ran a pilot study, asking patients to breathe air with not-harmful, slightly raised CO2 for 15 minutes. People without BD respond by panting a bit to try to clear the gas. Then, after a few more minutes on the enriched air, breathing levels off to save energy as the body learns that only so much CO2 can be removed.
In BD, however, breathing doesn’t stabilize. The response in many is unpredictable, going up and down, Mac-Kinnon says, “like a faulty cruise control.” Now he hopes a larger study will verify response to CO2 as a biomarker. Plus, a new ability to study how appetitive drive is regulated could reach to the heart of major depression, dementia, cognitive disorders and eating problems like anorexia.
MacKinnon notes that lithium, a mainstay of BD treatment, is known to enhance growth of neurons—a help with learning. “But people need more than medication to get better,” says MacKinnon. “I see this in my practice. Because patients with unstable moods don’t know if they’ll feel the same today about something as they did last week, their learning is imposed on chaos. They need encouragement, structure. They likely need repeated lessons, repeated episodes of doing something good and getting a reward.”