Lyme disease may increase risk of mental illness and suicidal behavior

Patients with Lyme disease are at an increased risk for any mental disorder, emotional disorders and suicidal behavior, according to new research.

Results of a large population-based study show that the rate of depression was 42% higher in patients with Lyme disease than in people who had no history of Lyme disease; the suicide rate was 75% higher, said lead author Brian A. Fallon, MD, professor of clinical psychiatry and director of the Lyme and Tick-Borne Diseases Research Center, Columbia University, New York City.

“Lyme disease is more than a rash, and although most patients improve when the disease is detected early, when it is not detected early, or when it is a more serious, clinicians should be aware that there may be psychiatric sequelae,” Fallon said. Medscape Medical News.

The results were published online July 28 in the American Journal of Psychiatry.

Increase in prevalence

Lyme disease, which is caused by bacteria carried by infected ticks, can lead to severe pain syndromes, debilitating fatigue and neurological problems. The prevalence of Lyme disease appears to be increasing in the United States as ticks spread beyond epicentres in the Northeast and Midwest, Fallon said.

Previous research has linked Lyme disease to depression, but those studies were either small or “otherwise flawed,” he noted. For example, patients may have been reluctant to participate in research conducted by psychiatric institutions, which could have skewed the results, he said.

For the current population-based cohort study, the researchers used linked Danish registers to collect information on patients who had been diagnosed with Lyme borreliosis and later received a psychiatric diagnosis.

From 1994 to 2016, 12,616 people received a hospital diagnosis of Lyme borreliosis (mean age at first diagnosis, 41 years). Most (90%) had general Lyme borreliosis and other non-neurological manifestations; the other individuals had neurological manifestations, including meningitis.

The comparison group included 6,933,221 people who had not been diagnosed with Lyme disease.

Fully adjusted models controlled for sex, age, calendar period, marital status, education level, socioeconomic status, and chronic medical comorbidity. The primary endpoint was any mental disorder.

Clinical awareness

The results of the fully adjusted model show that the rate of any mental disorder was 28% higher in participants with Lyme borreliosis than in those without (incidence rate ratio [IRR],1,28; 95% CI, 1.20 – 1.37).

For the secondary outcome of affective disorder, the investigator found a 42% higher rate in people with Lyme borreliosis compared to people without the disease (IRR, 1.42; 95% CI, 1.27 – 1.59).

In addition, the rate of suicide attempts was approximately double for the group with Lyme disease compared to the group without Lyme disease (IRR, 2.01; 95% CI, 1.58 – 2.55) .

After adjusting for age, sex, and calendar period, the rate of completed suicides was 75% higher among participants diagnosed with Lyme disease (IRR, 1.75; 95% CI , 1.18 – 2.58).

Although the absolute suicide rate is low, with just 25 deaths over a 22-year period, “even one suicide in my mind is too much,” Fallon said.

“If we can educate doctors about the mental health consequences of Lyme disease, and if it makes them more alert and asks more questions about depression and suicidal thoughts, that would be a really good outcome of this study,” he added.

“Logical Biological Connection”

Research has also revealed a “dose-response.” The higher the number of hospital contacts for Lyme disease, the higher the rates of diagnoses of mental disorders.

Additionally, the analysis generally showed that rates of mental disorders were much higher in the first year after Lyme disease diagnosis, after which rates declined somewhat.

To determine whether disorders other than mental health disorders were affected after Lyme disease, investigators assessed the rate of fractures not involving the skull or spine. Compared to the rates of such fractures, the rates were two, three and seven times higher for mental disorders, emotional disorders and suicide attempts, respectively.

However, there was an increased rate of fractures after a hospital diagnosis of Lyme borreliosis. Fallon said this could be due to the use of prescription psychiatric drugs that are associated with an increased risk of fractures.

Mechanisms linking Lyme disease to mental illness could include immune activation and increased inflammation.

“There is a very logical biological link between inflammation and altered neurotransmitters,” Fallon said. He noted that research has linked depression to increased inflammation in the brain and that “the whole cascade of neurotransmitter effects that accompany inflammation can lead to symptoms of depression.”

Physical factors and other factors related to Lyme disease could also play a role, Fallon said. “The pain associated with Lyme disease may lead to an increased rate of depression; deep fatigue may make it difficult for people to work or think and therefore lose their economic stability,” he added.

Fallon noted that because the study focused on outpatient, inpatient, or emergency department hospital contacts, it did not include patients who had been treated by community physicians.

The study looked at Lyme borreliosis in Denmark, where the predominant genospecies differ from the United States. The most common strain in the United States causes a more robust inflammatory response. Thus, rates of mental disorders and suicidal behavior after Lyme disease may be even higher in the United States than in Denmark, Fallon said.

Methodological problems?

Commenting on the findings of Medscape Medical NewsPaul G. Auwaerter, MD, Sherrilyn and Ken Fisher Professor of Medicine and Clinical Director, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, said some “weight” should be given to studies like this that use the Danish National Patient Registry.

However, the small absolute numbers of some mental health disorders in the study “make the significance uncertain, as minor changes could cause the results to vary,” he noted.

Auwaerter, who was not involved in the research, added that the study used a different registry for mental health disorders, which could create “a methodological problem” that weakens the results.

He pointed out that studies of a link between infections and mental disorders are not unique to Lyme disease. Other studies have looked at the possible link between certain viruses and schizophrenia; in some of these studies, the link has not been confirmed, he said.

Additionally, Auwaerter noted that the study only reported association, not causation.

The study was funded by the Global Lyme Alliance Inc.. Investigators report no relevant financial relationships. Auwaerter has received support from Pfizer, Ixodes and Medical-legal.

Am J Psychiatry. Published online July 28, 2021. Summary

For more information about Medscape Psychiatry, join us on Facebook and Twitter.