Hopkins Medicine Magazine - go home
Current Issue Past Issues Talk to Us About the Magazine Search
an online version of the magazine Spring/Summer 2007
Despite nearly two decades of studies linking depression, anxiety, and heart disease, medicine has mostly declined to invite mental health experts into the solution. Roy Ziegelstein and friends want to change all that.
Illustrations by Whitney Sherman
  Despite nearly two decades of studies linking depression, anxiety, and heart disease, medicine has mostly declined to invite mental health experts into the solution. Roy Ziegelstein and friends want to change all that.

By ramsey flynn

Betty Schneider* dreads the coming of night. She has her reasons. The last time death stalked her in earnest, it crept into her house at 2 a.m., when she was sleeping in bed next to her husband. Chest pain. Breathing trouble. Sweat. “You have to get me an ambulance,” she told her husband. By the time all the fuss was over, she had only half a working heart left. How can she trust falling asleep? So she worries about the ending of the day, watching TV shows with her 2-year-old terrier until the Ambien finally puts her out—well past the time of her previous near miss, sometime after 3 a.m.

If they gave out awards for depression, Schneider would be a top contender. Her husband died last fall. She rarely sees her grandkids. She’s tired all day, every day. She’s sad most days. She doesn’t enjoy hobbies, not even reading. She doesn’t trust the ticker that beats so wanly in her chest—not even with its fancy new pacemaker-defibrillator. On top of it all, she’s got a host of other ills that compel her to take some 15 medicines a day, constantly straining the limits of her tiny fixed income.

This grinding clinical sadness is a beast that has ruled much of Schneider’s life for at least eight years. Roy Ziegelstein, a Johns Hopkins cardiologist, researcher, and Miller Family Scholar, thinks the beast has magnified Schneider’s heart disease. He believes chronic sadness and heart disease are a particularly toxic combination, feeding on each other like parasites in partnership.

3 1 2
> Despite a rising tide of high-quality research in favor of this connection, Ziegelstein says he’s heard too many perfectly smart cardiologists say things like “stress is overrated” as a driving factor in heart disease.

And he’s not talking about the “Broken Heart Syndrome” recently described by his other Hopkins colleagues. That condition comes from a sudden flare-up of emotions that can cripple the heart and mimic a heart attack. No, this is different. Ziegelstein is focused on the long-term feelings that change a person’s biological makeup cell by cell. 

“Too many physicians just don’t see the obvious connections between a person’s emotions and his or her heart function,” says Ziegelstein. Despite a rising tide of high-quality research in favor of this connection, he says he’s heard too many perfectly smart cardiologists say things like “stress is overrated” as a driving factor in heart disease. He understands how medical scientists all want to work with tangible things like lipids and lipoproteins. He understands why skeptics would doubt that a person’s feelings would cause a buildup of plaques in their arteries that would put them at greater risk of dying after a heart attack.

But after playing a role in more than 30 studies on the topic during the past 13 years, Ziegelstein has stuck to his guns. He now feels strongly that Betty Schneider and an untold number of other cardiac patients around the world have suffered the mind-and-heart connection in the worst way. And he’s out to change the way modern medicine responds to them.





Roy Ziegelstein’s epiphany happened this way: In 1993, he saw a patient in his office who had just survived a major heart attack. He remembered how sick the man had been just a few weeks earlier, when he was hooked up to a respirator. Now the same person was vertical, walking, and talking. And when Ziegelstein asked him the standard checklist review of symptoms, the patient reported nothing alarming—“no,” “no,” and “no.”

Satisfied that the patient was doing well, Ziegelstein smiled and sent him back into the world. Hours later, the man’s wife called. She wanted to hear directly from the doctor himself how he really thought her husband was doing. “I think he’s doing great,” Ziegelstein said confidently, then thought it wise to compare notes with the patient’s spouse: “How do you think he’s doing?”

Long silence.

Then, finally: “Terribly,” the woman said. She proceeded to detail how her husband was showing little interest in much of anything. He hadn’t eaten lunch or dinner that day. He even passed up his chances to meet with friends over their normal game of billiards, choosing instead to linger on the sofa, passing the hours in silence. She was worried. Her husband was alive, but he was behaving almost like a dead man.

What an idiot I am, Ziegelstein thought. For all of his rigorous adherence to the latest ideas in cardiac care, Ziegelstein felt crippled with professional myopia. His reliance on the received wisdom—where a time-tested list of physical symptoms was thought to provide everything a physician needed to know about a cardiac patient’s condition—had deprived him of the ability to see other monsters lurking nearby.

Of course, it was broadly accepted by then that up to 30 percent of patients recovering from a heart attack suffered bouts of depression. But scientists had just begun to understand that depression in this setting could have serious consequences. Those who suffered from it were more likely to die from heart disease in the months after the heart attack that hospitalized them in the first place.

But what about the idea that undetected depression might be one of the primary causes of heart disease? Since studies have shown that a high percentage of patients with heart disease also suffer depression, what comes first, the heart disease or the depression?

Unfortunately, says Ziegelstein, scientists disagree. But he thinks that’s changing. He thinks the best studies show depression contributes to the initial formation of heart disease, and that the scientists behind those studies are starting to prevail.

The differing camps have been building bridges, Ziegelstein explains, connecting emotional chemistry to brain chemistry to blood chemistry to muscle chemistry to vascular chemistry. They have lately been tracking the way neurotransmitters that normally communicate between nerve cells are also abundant in blood platelets, which tend to be more “sticky” in patients with heart disease. In a 2007 article that he co-authored in the American Journal of Medicine, Ziegelstein showed that heart disease patients who received antidepressants known as selective serotonin reuptake inhibitors had slightly better cardiac outcomes than patients not receiving these medications (at the expense of some increased risk of bleeding). It was as if the antidepressants—which act on serotonin in the brain—might also be affecting serotonin in platelets, thereby affecting blood clot formation.





Ziegelstein’s campaign to associate states of mind with physical health is winning converts both within and outside Hopkins. Take the case of Charlie Lowenstein, a lab scientist here who recently confessed in a group presentation that he’d initially found Ziegelstein’s heart-mind notions “goofy.” That was until Lowenstein’s once light-hearted 9-year-old son developed increasingly sour moods, rarely able to smile. His boy’s growing displays of depressive symptoms forced Lowenstein to consider the value of using a selective serotonin reuptake inhibitor in his own child, which compelled him to more deeply study the essential functions of the neurotransmitters.

In the course of his newly personalized odyssey, Lowenstein and his research partner, pathologist Craig Morrell, began to identify signaling pathways among blood platelets that might explain the fundamental mechanisms of how they can wreak so much harm on the human heart. Along the way, Lowenstein has begun to embrace Ziegelstein’s work. “The relationship between depression and heart disease is more plausible to me now,” Lowenstein says. “There’s clearly a biological connection between neurotransmitters and platelets. The two systems use the same signaling molecule.”

While Ziegelstein thinks such independent testimony is encouraging, he also still thinks the revolution remains too far behind the available evidence. In March, he gave a wake-up talk at the annual gathering of the American Psychosomatic Society titled: “Why Don’t Cardiologists Care About Depression and Anxiety?” His message to cardiologists is becoming more strident. “If you don’t attend to the patient’s depression,” he says, “you’re really only half a doctor, in my view. And half a doctor is as good as no doctor.”

3 1 2
> Ziegelstein’s message to cardiologists is becoming more strident. “If you don’t attend to the patient’s depression,” he says, “you’re really only half a doctor, in my view. And half a doctor is as good as no doctor.”

Ziegelstein wants a more collaborative system of care between mind experts and heart experts. The connections, he says, “warrant fundamental changes to our approach.”

“I think he’s 100 percent correct on this,” says Allan Jaffe, a prominent expert in the development of acute ischemic disease at the Mayo Clinic who says his work parallels that of Ziegelstein’s team. But Jaffe is not optimistic. He says the change would require a dramatic shift in medical culture, and he thinks the MDs are the chief resisters. He says physicians too often see aspects of mental health as lacking scientific rigor—making the notion of a broad collaboration in the name of behavioral cardiology a frustrating non-starter.

David Hellman, who oversees the Department of Medicine on the Hopkins Bayview campus where Ziegelstein works, sees Ziegelstein as one of the pioneers in a discipline that has traditionally avoided building bridges. “But Roy is not the only pioneer,” Hellman points out. One of Ziegelstein’s chief research partners is clinical psychologist Jennifer Haythornthwaite, who directs Hopkins’ Center for Mind-Body Research. In their collaborations, Hellman sees Ziegelstein and Haythornthwaite as “building bridges toward each other. There’s not a lot of traffic crossing those bridges yet, but they are less alone.”






Ziegelstein says he’s learned over the years to listen more closely to his heart patients. In one recent case, a medical student was assisting him in the clinic and spent 45 minutes evaluating a patient before Ziegelstein arrived. The student reported that the man was obese, lived a sedentary lifestyle, and smoked. There was no mention of depression. But Ziegelstein had learned the hard way that—while the usual battery of questions might aid in finding some causes of heart disease—it had proven completely tone-deaf to signs of depression. Ziegelstein took his turn with the patient.

“Can you stop smoking?” Ziegelstein asked.

“No,” said the patient.

“Okay,” Ziegelstein rejoindered. “Will you exercise?”

“That might help,” the patient allowed.

“But will you do it?” Ziegelstein pressed.

“If I care about it,” the man hedged, “I can do it.”

Aha, thought Ziegelstein, now we’ve opened up Pandora’s box.

The giveaway, Ziegelstein later told the student, was “If I care.” That teensy phrase opened a line of questioning into what most cardiologists would have ignored or perhaps considered the realm of mental health experts. In Ziegelstein’s case, it allowed a further exploration showing the man was now in his second marriage, had kids from his first, was undergoing financial hardship, and had a weak social support network. Though the man was employed, much of his income was going to alimony and child support.

This patient soon came up positive for signs of depression.

While Ziegelstein agrees with the popular notion that most people who have suffered a cardiac event will naturally brood over their brush with death and become more anxious or sad, he has become increasingly alarmed that patients recovering from a heart attack are not formally screened for signs of more serious depression. He decided to put some weight behind this idea. He headed up a study here co-authored with seven other partners, three of whom were mental health experts. The driving question was simple: Can doctors and nurses recognize the signs of depression in patients without special screening while the patients are still in the hospital recovering from a heart attack?

Their findings, published in a 2005 issue of Psychosomatic Medicine, were an eye-opener. In short, the answer was no, doctors and nurses proved dramatically unskilled at detecting signs of depression. Without any formal screening, the providers missed three out of four patients with symptoms of depression. 

Given the long-standing findings that untreated depression in heart attack survivors raises the risk of death in the ensuing months after hospital discharge, how could providers dismiss the value of formal screens?





For patients like Betty Schneider, even the two-doctors-in-one idea is having limited success. For all of her 15 daily medicines and weekly group therapy sessions, her outlook on life remains chronically blue.

She has her reasons. Sad events surround her. After getting his own six-way heart bypass several years ago, her husband died in October, of cancer. He may have been an especially grumpy husband, she admits, but he was company. Then, seemingly all within a 10-day period, four long-term neighbors and friends on her block all died in quick succession.

Her sweet terrier, Biscuit, “has more ambition than I have,” says Schneider. When Schneider attempts to walk Biscuit on a leash, the exhilarated terrier strains forward, taxing her beloved owner.

Ziegelstein says the medicines can only go so far. Her diabetes means blood sugar issues. Her hypertension requires its own management, even if her heart muscle still has adequate pumping capacity. The antidepressant medicine remains a simple band-aid against larger life issues.

But Betty Schneider and Roy Ziegelstein share one key area for optimism about the patient’s health. Schneider’s son-in-law has been looking for a new family home in Pennsylvania. He and his wife want it to come with a mother-in-law apartment. The son-in-law has made it clear to Schneider that they would like her to move in with them. She would have room. Biscuit would have the run of a big yard, no leashing necessary. The most satisfying relationships in her life—simple exchanges with her daughter and two grandchildren—would become abundant. To Roy Ziegelstein’s way of thinking, intangibles like those could provide the best medicine yet for Betty Schneider’s worried heart.” *

 Music on the Mind
 The Protectors
 Practicing On Plastic
 Troubled minds, troubled hearts
 Circling the Dome
 Medical Rounds
 Annals of Hopkins
Class Notes
 Our Man in Nashville
 Learning Curve
Johns Hopkins Medicine

© The Johns Hopkins University 2008