Unraveling the mystery of Lyme disease

Long before the SARS-CoV-2 virus was linked to a syndrome we now call long COVID, researchers and clinicians were already debating over how to best assist patients experiencing lingering symptoms from Lyme disease. For reasons that are unclear, 10% to 20% of people who contract Lyme disease report ongoing or intermittent symptoms at least a year after completing antibiotic treatment, including fatigue, muscle aches, difficulties with memory, irritability, and other symptoms, according to a review of the research (Marques, A., Infectious Disease Clinics of North America, Vol. 22, No. 2, 2008)opens in new window.

For patients, these ongoing and sometimes debilitating symptoms can erode their quality of life, potentially leading to depression, anxiety, and other mental health issues. But over the past few decades, researchers have also determined that the tick-borne infection itself, along with related inflammatory and other physiological effects, may directly cause mental health disorders.

One recent study, conducted by researchers from the Columbia University Irving Medical Center and the Copenhagen Research Centre for Mental Health, found that patients who received a hospital diagnosis of Lyme disease had a 28% higher rate of mental disorders and were twice as likely to have attempted suicide postinfection than individuals without a Lyme diagnosis (Fallon, B. A., The American Journal of Psychiatry, Vol. 178, No. 10, 2021)opens in new window.

Patients diagnosed with Lyme report a range of mental health-related symptoms. Some experience panic attacks for the first time, which can sometimes extend for hours at a stretch, said Sheila M. Statlender, PhD, a clinical psychologist in Newton, Massachusetts, who has been working with patients with Lyme disease for more than 15 years. Some report frustrations with “brain fog,” cognitive difficulties that can include impaired concentration or trouble with tracking words on a page. In rarer instances, they develop auditory hallucinations. “They hear music, or they hear a radio that’s not playing,” she said.

In other circumstances, patients may arrive for therapy with a mental health diagnosis, such as anxiety or depression, unaware that a tick bite lies behind their symptoms, said Judith G. Leventhal, PhD, a clinical psychologist and neuropsychologist based in New York City.

Leventhal and Statlender are part of a small cadre of psychologists who now specialize in treating individuals who have been diagnosed with Lyme, a disease that remains as controversial as it is increasingly common. An estimated 476,000 cases were diagnosed each year from 2010 through 2018, according to a recent analysis of commercial insurance claims data (Kugeler, K. J., et al., Emerging Infectious Diseases, Vol. 27, No. 2, 2021 [PDF, 650KB]opens in new window). While the bulk of cases have been reported in the Northeast, mid-Atlantic, and upper Midwest regions of the United States, cases have been found throughout the countryopens in new window.

Lyme, which occurs when an infected tick transmits a bacterium called Borrelia burgdorferi, is one of various diseases spread by ticks. It’s also a polarizing subject on multiple levels, from the lack of consistently reliable blood testing to an ongoing debate over how to treat or even describe patients who experience longer-term symptoms, including mental health symptoms (see Controversy: Split over treatment for persistent symptoms). The patient community often uses the terminology of “chronic Lyme disease”; other terms include “posttreatment Lyme disease” and “posttreatment Lyme disease syndrome” (Sotsky, J., Psychiatric Times, Vol. 39, No. 1, 2022)opens in new window.

Despite the complexities involved in detecting and treating Lyme, New York City psychiatrist Brian Fallon, MD, MPH, director of the Lyme and Tick-Borne Diseases Research Center at Columbia University Irving Medical Center and lead author on the Danish hospital study, credits mental health practitioners, including psychologists, with alerting physicians in the early days of Lyme disease diagnoses that something unusual was going on with these patients.

“They were often the ones who were saying, ‘Look, I don’t think this is just depression. I don’t think this is just irritability,’” said Fallon, one of the first clinicians to link the tick-borne disease to neuropsychiatric symptoms. “‘This patient is also having sound sensitivity and light sensitivity and complaining of numbness and tingling and cognitive problems. This doesn’t make sense.’”

Symptoms of Lyme may include fever, chills, and muscle aches. At least 70% of adults and children will develop some type of skin irritation around the bite, including a rash called “erythema migrans” that’s been described as having a bull’s-eye appearance, according to the Centers for Disease Control and Prevention (CDC)opens in new window. Ideally, the patient is diagnosed shortly after the bite so antibiotics can be started. While early Lyme disease can be readily diagnosed during the first month if the typical erythema migrans rash is present, later stages with clinical symptoms require blood testing for antibodies to help clarify the diagnosis, Fallon said.

It is important to know that if the test is performed too soon after the infection, the antibodies may not have had time to fully develop. Most people recover after treatment, according to CDC officials.

But some people may never realize that a tick has bitten them, said Statlender, whose family dealt with the disease before she began to see patients with Lyme in her practice. (Her three children, who became ill in the 1990s and have since recovered, weren’t diagnosed for at least several years in part because they didn’t notice the tick bites.) The rash can emerge in various forms, and it can be hidden along the hairline, Statlender said. Among people with darker skin, it may not be easily visible.

Depression, anxiety, or other mental symptoms may be among the first signs of infection, as happened with Lorraine Johnson, JD, MBAopens in new window. The attorney, an avid hiker in Southern California, was diagnosed with major depression in the late 1990s after experiencing changes in mood and thinking, including concentration.

“If you are misdiagnosed with a psychiatric illness, you will be treated with psychotropic medications, and those are not without side effects,” said Johnson, now the chief executive officer of LymeDisease.orgopens in new window, a nonprofit patient research, advocacy, and educational organization. “And they may lead you on a road to nowhere. That’s basically what happened to me for about 5 years.”

At some point, Johnson recognized that she had been misdiagnosed, “because none of the medications were working,” she said. Once her Lyme disease was identified, she completed two years of aggressive medical treatment, including antibiotics, and her symptoms cleared, including her mood. She has not experienced any depressive episodes since. Along with heading up LymeDisease.org, she is also the principal investigator of their patient registry, MyLymeData, which has collected and analyzed data from more than 16,000 patients.

The potential for misdiagnosis on the medical side makes it challenging for psychologists to pinpoint whether a patient’s depression or anxiety could be caused by Lyme, Statlender said. Psychologists should look out for any sudden onset of symptoms, she said. An adult patient may experience panic attacks or anxiety for the first time, or a high-achieving student may begin to struggle in school.

Kristin Penza, PhD, a clinical psychologist in Norwell, Massachusetts, who conducts neuropsychological evaluations primarily of children and young adults, including those with Lyme disease, agreed that sudden onset is key, particularly if the patient has developed multiple mental health symptoms around the same time. For instance, an adolescent might describe new occurrences of severe anxiety at night, insomnia, and difficulty in concentrating at school. As part of the evaluation, Penza will also ask if they have experienced any physical symptoms.

In another scenario, a student may be sent to therapy for a seeming behavioral issue that is actually rooted in Lyme-related sensitivities, such as to the fluorescent lights or to the noise of crowded school hallways, Penza said.

“They feel overwhelmed,” she said. “They can’t even get into the school, or they sit on the stairwell. And they’re seen as defiant. But really, they’re on sensory overload and they just can’t handle walking into that building or walking into that classroom.”

In regions where tick-borne diseases are common, psychologists should refer any patient they are concerned about to a physician for testing to rule out that possibility, Leventhal said. “Because they are treatable,” she said. “You can’t ignore the fact that microbes cause many different neuropsychiatric symptoms. Certainly, Lyme disease and other tick-borne diseases are prominent on that list.”

A tick-borne infection should also be considered if a patient does not respond to treatment efforts, including medication, Leventhal said. Medications such as antidepressants or antianxiety medications by themselves may not relieve or reduce someone’s symptoms because they may be driven by an underlying infection-induced encephalopathy, she said. Thus, psychiatric symptoms need to be seen within the context of neurocognitive impairments to assess the presence of an encephalopathy. To that end, a neuropsychological evaluation is an important diagnostic tool that can provide key information for treatment decisions.

Another potential red flag is if a patient’s symptoms change while they are taking antibiotics for another medical reason, such as to treat an infection, according to a screening tool that Statlender has created for mental health professionals. That’s because some patients can develop what is called a Jarisch-Herxheimer (J-H) reaction, in which, paradoxically, their physical or neuropsychiatric symptoms may temporarily worsen during initial antibiotic treatment, a phenomenon thought to be due to the die-off of the disease-causing bacteria, and a sign that the treatment is working.

In the early 1990s, Fallon, whose expertise includes hypochondria, started getting referrals of patients who had been told that they had that psychosomatic disorder. But, because these patients didn’t have any history of illness anxiety, Fallon began to believe they had contracted Lyme disease. Plus, they reported the sudden onset of fatigue, joint pain, cognitive difficulties, and other symptoms. Around the same time, he began to meet with families who had been impacted by Lyme in nearby Connecticut. They reported not having experienced anxiety, depression, and other mental health symptoms until after contracting the tick-borne illness.

Fallon and his wife, fellow psychiatrist Jenifer Nields, MD, of the Yale School of Medicine, laid out the case for a potential link between Lyme disease and later neuropsychiatric symptoms. They cited research, including case reports, showing that patients can subsequently develop major depression, anxiety, panic attacks, and numerous other symptoms, including auditory and visual hallucinations (The American Journal of Psychiatry, Vol. 151, No. 11, 1994)opens in new window.

More recently, Fallon teamed up with Danish researchers on the hospital study to take a more comprehensive look at to what degree Lyme disease boosts vulnerability to later mental health issues. The analysis, which the researchers described as the first large, population-based study to assess that relationship, also found that the likelihood of being diagnosed with any mental health disorder following a Lyme diagnosis—based on patient records from 1994 through 2016—was 28% higher overall and 42% higher for affective disorders, according to the 2021 study in The American Journal of Psychiatryopens in new window.

Those patients, Fallon noted, were ill enough to get a hospital-based diagnosis, whether that was during an outpatient visit or while being admitted. “This should not be seen as a study for run-of-the-mill Lyme rash,” he said. “It really is a study on those patients who had severe enough symptoms that they had to go to the hospital.”

The connection between a bacteria and mental health symptoms is not new, Fallon said, offering syphilis as one example. Both syphilis and Lyme are caused by a corkscrew-shaped bacterium called a spirochete.

Researchers are still unraveling the precise mechanisms involved, but there is clearly an inflammatory connection, Fallon said. “It’s definitely very well accepted to say that any infection that can cause an encephalitis, which means inflammation in the brain, can cause psychiatric disorders,” he said. “Any infection can do that, and Borrelia can do it as well.”

Fallon and others who treat these patients note that their mental health symptoms can manifest in ways that may differ from individuals who haven’t contracted Lyme. Joseph Trunzo, PhD, a professor and chair of psychology at Bryant University in Rhode Island who works with patients who have anxiety disorders, said one notable hallmark is the duration and acuity of the anxiety without any seeming underlying triggers.

“In Lyme-driven anxiety, people will often feel this really intense, prolonged, almost nonstop, very high anxiety,” he said. “It might not be a full-blown panic attack, but it’s pretty high to the point where it’s extremely uncomfortable and very distracting and makes it difficult for them to function.”

As psychologists take a patient history, it is important to ask about any sensitivities, such as to light or sound, that can be associated with Lyme, Trunzo said. Patients will often volunteer those sensitivities, as they can be quite distressing, he said. A person may not be able to leave their home, for instance, without wearing sunglasses to protect their eyes from strong light. “It really feeds into isolation,” he said. Moreover, these individuals may exhibit an elevated degree of impulsivity and emotional lability related to their encephalopathy. This can be directed toward others or themselves and in some cases may increase their risk of suicide, he said. The disruption to their lives, which may include the loss of a job or a falling-out with friends, may heighten their vulnerability as well, he said.

“A lot of times, people don’t really know what’s going on. They’ve been feeling really ill and very sick—oftentimes for a very long time—and they haven’t been able to get any help or any relief,” Trunzo said. “It puts people in a very desperate situation and very desperate straits.”

Pegah Touradji, PhD, a neuropsychologist and assistant professor of physical medicine and rehabilitation at Johns Hopkins University who works with adults with posttreatment Lyme disease, agreed that adjusting to chronic illness can inflict mental health strain. As people dial back their daily activities to limit pain and fatigue, these life changes can be upsetting, said Touradji. “For some people, the reaction to that stress can manifest in mood symptoms,” she said.

Patients report hiding their diagnosis at work, as well as from all but a tight circle of family and friends, fearing stigma and thus boosting their sense of isolation, said Johnson. They may not feel supported even by their own physician, she said.

“Being gaslit by a medical professional is really painful for patients,” she said. “It’s the same thing as being dismissed, or your reality being denied.”

Initially, patients struggling with symptoms of a tick-borne disease may need a lot of information about these diseases, as well as validation of their experience, Leventhal said. She described a teenager who was being treated for a tick-borne infection and was experiencing intrusive thoughts. Reassurance that her brain was playing tricks on her was a helpful concept for her.

Patients may be coping with a high degree of demoralization, given their frustrations with the medical establishment, which psychologists must address up front, said John Keilp, PhD, a Lyme researcher and consulting neuropsychologist who works with Fallon at Columbia’s Lyme and Tick-Borne Diseases Research Center. It’s crucial that psychologists read up on Lyme and the related controversies through the years, including related to diagnosis, he said.

“Do a little homework to get a sense of what the historical backdrop has been over the last 20 or 30 years,” he suggested, “because that will give you a better feel for what the patients have gone through in terms of their frustrations with the medical establishment or with the people they’ve gone to see.”

To assist mental health practitioners, Trunzo recently teamed up with Leventhal, Statlender, and several other colleagues to write a detailed primer about the diagnosis and treatment of tick-borne diseases, which also includes Statlender’s screening tool (Practice Innovations, online first publication, 2022). Trunzo, who considers himself a proponent of cognitive behavioral therapy (CBT), has discovered over time that CBT’s homework-intensive approach, which may include keeping a diary or daily log, can overwhelm those coping with brain fog, extreme fatigue, and other moment-to-moment challenges.

Identifying and helping to change dysfunctional and distorted thought processes, another aspect of CBT, does not make as much sense with these patients either, Trunzo noted. “A lot of the thoughts that people have around Lyme disease are not necessarily distorted, right? ‘I lost my job. I’m really sick. I can’t do any of the things that I used to be able to do.’”

Instead, Trunzo has had some success incorporating acceptance and commitment therapy (ACT), which he described as less reliant on restructuring one’s thought patterns and more on adapting to current reality. There have been no evidence-based studies yet conducted in patients with Lyme, but other research has shown the approach to be effective in those with other chronic illnesses, he said.

Under the ACT approach, a patient will still identify and notice the thoughts that they’re wrestling with, Trunzo said. But the therapy focuses more on learning to coexist with or accept those thoughts so that they don’t divert individuals from living in the moment.

With ACT, patients can also begin to think about their values as they reframe their lives moving forward, Touradji said. They may not be able to return to their job, but they can consider what it is they value about the work and incorporate that into their life. Someone who was a nurse in a pediatric clinic and wants to continue helping people could instead volunteer at an elementary school, she said.

A common theme emerges from Touradji, Trunzo, and other psychologists: Assisting and caring for patients with Lyme disease requires an open mind, flexibility in thinking, and a willingness to try a mix of therapeutic approaches.

“There is no question, it is a very, very challenging population to work with,” Trunzo said. “It also can be very rewarding. You can have an immeasurably profound impact on someone’s life by doing this work. Because you may very well be the only person who is listening to them.”