Lyme Disease May Up Risk for Mental Illness, Suicidal Behavior

Patients with Lyme disease are at increased risk for any mental disorder, for affective disorders, and for suicidal behavior, new research suggests.

Results from a large population-based study show that the rate of depression was 42% higher among patients with Lyme disease than among persons who did not have a history of Lyme disease; the rate of suicide 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 while most patients get better when the disease is caught early, when it's not caught early or when it's a more serious case, clinicians should be aware there may be psychiatric sequelae," Fallon told Medscape Medical News.

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

Increasing Prevalence

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

Previous research has linked Lyme disease with depression, but these studies were either small or "flawed in some other way," he noted. For example, patients may have been reluctant to participate in research carried out by psychiatric institutions, which could have biased the results, he said.

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

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

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

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

Raising Clinical Awareness

Results from the fully adjusted model show that the rate of any mental disorder was 28% higher among participants with Lyme borreliosis compared with those without the disorder (incidence rate ratio [IRR],1.28; 95% CI, 1.20 – 1.37).

For the secondary outcome of affective disorders, the investigator found a 42% higher rate among individuals with Lyme borreliosis in comparison with persons who had not had the disease (IRR, 1.42; 95% CI, 1.27 – 1.59).

In addition, the rate of suicide attempts was about double for the group with Lyme disease in comparison with 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 who had been diagnosed with Lyme disease (IRR, 1.75; 95% CI, 1.18 – 2.58).

Although the absolute rate for suicide was low, with only 25 fatalities over a 22-year period, "even one suicide in my mind is too many," said Fallon.

"If we can raise awareness among physicians that mental health consequences can occur with Lyme disease, and if that makes them more vigilant and ask more questions about depression and suicidal thoughts, that would be a very good outcome of this study," he added.

"Logical Biological Connection"

The research also revealed a "dose response." The greater the number of hospital contacts for Lyme disease, the higher the rates for mental disorder diagnoses.

As well, the analysis generally showed that rates of mental disorders were much higher during the first year after the Lyme disease diagnosis, after which the rates dropped off somewhat.

To investigate whether disorders other than mental health disorders were affected after Lyme disease, the investigators assessed rate of fractures not involving the skull or spine. Compared with rates for such fractures, rates were two-, three-, and sevenfold higher for mental disorders, affective disorders, and suicide attempts, respectively.

However, there was an increased rate of fractures after a hospital-based diagnosis of Lyme borreliosis. Fallon said this may be attributable to use of prescription psychiatric medications that are associated with an increased risk for fractures.

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

"There's a very logical biological connection between inflammation and altered neurotransmitters," said Fallon. He noted that research has linked depression with increased inflammation in the brain and that the "whole cascade of neurotransmitter effects that go along with inflammation can lead to depression symptoms."

Physical factors and other factors related to Lyme disease could also play a role, Fallon said. "It could be that pain associated with Lyme disease leads to an increased rate of depression; it could be profound fatigue makes it hard for people to work or to think and as a result are losing their economic stability," he added.

Fallon noted that because the study focused on hospital contacts in the outpatient, inpatient, or emergency department setting, it did not include patients who underwent treatment by physicians in the community.

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

Methodologic Problems?

Commenting on the findings for Medscape Medical News, Paul 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 such as this one that use the Danish National Patient register.

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

Auwaerter, who was not involved with the research, added that the study used a different registry for mental health disorders, which could create "a methodological problem" that weakens the findings.

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

In addition, Auwaerter noted that the study reported only an association, not causation.

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

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

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