• Rosalie Greenberg, MD

Tick-borne Illnesses and Suicidal Thoughts/Behaviors in Youth



As I was looking at the weekend edition of the New Jersey Star Ledger , a major newspaper in my state, on Sunday, March 5, 2022 I was struck by an exceptionally lengthy article entitled, “Saving Charlie.”1 Reporter Adam Clark chronicled the struggles of a highly suicidal teenager and his family’s ongoing efforts to get him proper help. Sadly, this 16-year-old was obsessively preoccupied with ending his life which resulted in at least seven serious suicide attempts over the previous two years. The article highlighted how the mental health crisis in this state is getting worse and better intervention is needed. The writer commented that there are “Suicidal teens languishing in emergency rooms. Spiraling students waiting months for an appointment with a child psychiatrist. Increasingly younger children self-harming and attempting suicide.” Sadly, these observations are applicable to the rest of the country and are not just a New Jersey problem.

As a child and adolescent psychiatrist with over 40 years of experience, I am convinced that youth today are sicker, and in multiple ways. Half of adult mental illness begins by age 14.2 Not only are mental disorders starting earlier, but rates are on the rise. For too many parents, the rise in rates of suicide attempts and death by suicide, especially in the last two decades, is a grim reality that happens too close to home.

In the 1980s and 1990s the top three causes of death in young people were accidents, followed by homicide and then suicide . The numbers have changed. We are living in a time when death by suicide in our young people is occurring more frequently and earlier in life. According to the Centers for Disease Control and Prevention (CDC), between 2007 and 2018 the rate of suicide among 10-24-year-olds increased nearly 60%3. Meanwhile from 2007 to 2017 in the narrow 10-14-year-old age group the suicide rate nearly tripled. By 2017 the suicide rate in youth became more than twice the homicide rate, putting suicide as the number 2 cause of death in young people.

The problem of suicidal attempts and death by suicide is not just limited to the United States. Since 2010 the incidence of suicide attempts among children has increased globally.4 One study compared suicide rates in 81 countries in children aged 10–14 years over two decades: 1990–1999 and 2000–2009. The authors found that although variability in rates exist across different countries, in part due to different reporting methods, child suicide is an important public health issue worldwide.

During the COVID pandemic, suicide rates and attempts increased in many places, but it’s clear that for years something unrelated to COVID has been driving the surge in kids wanting to, and sometimes succeeding at, ending their lives. In 2020, the CDC noted that there appeared to be a differential effect on suicide rates by sex as the increase in attempts was much greater in girls than boys (50.6% vs. 3.7%).3

What makes this situation more dramatic is that it is well-known that the numbers of suicides and attempts are biased by underreporting.7 Deaths that are reported as accidents such as by drowning, falls or poisoning are potentially in reality mislabeled suicide. Especially if the cause of death is uncertain - like someone dying from a drug overdose- was it purposeful or accidental? The result might not be counted in statistical analyses. The ramifications in certain religions and concern for the family’s situation may make another cause of death be listed instead of suicide.

Studies indicate that more than 90% of children who die by suicide have a mental health condition,2 especially mood disorders. What is making our kids so ill? Without question, the answer is multifaceted.

One possible answer which is greatly overlooked, is related to infectious agents, and the inflammation and resulting immune dysfunction these pathogens can cause. In the medical literature a number of infections have been associated with suicide, including hepatitis C, HIV/AIDS, influenza, cytomegalovirus, coronaviruses including SARS-COV-2 infection (COVID-19), and the parasite toxoplasma gondii. The accumulating medical evidence strongly implicates inflammation and immunologic change playing important roles in the development of mood disorders, especially depression and bipolar disorder.7,8

Could it be that one road to this most dire outcome, suicide, begins with an infectious illness, followed by the development of a mental disorder, resulting in the development of suicidal thoughts and for some, culminating in eventual suicide? What evidence exists to support this possible sequence of events?

Denmark has maintained very detailed health care records on its population for several years. This database has served as the foundation for many important large scale medical studies. A few are quite relevant to the issue discussed here: the connections between infections and mental disorders, suicide attempts and death by suicide in different age groups.

One Danish study reviewed over 7 million medical records covering a 32-year period (1/1/1980-12/31/2011).9 Investigators looked at only hospital linked contact which included inpatient, outpatient and emergency room visits. Statistical analyses found that there was an association between hospitalization with infection and an elevated risk of suicide. The number of infections and amount of time the individual remained in the hospital appeared to show what’s called “a dose-response relationship.” This means that those with more hospital contacts due to infections were at heightened risk for suicide. This type of relationship is also observed with the interaction of length of hospital treatment and death by suicide. Consistent with this observation, the authors found that those with seven or more infections, as well as those who were hospitalized for more than three months, had the highest risk for suicide.

The authors extrapolated from their study that hospitalization for infections was associated with 10% of all suicides in Denmark. They did not claim that this was a causal relationship but acknowledged that there is a connection. But if causality were to be true, this leads one to believe that rapid treatment and early elimination of infections could help prevent one in 10 suicides.

Interestingly, it appeared that the risk for suicide in those who had already had psychiatric difficulties before the onset of infection was lower than in those whose psychiatric illness began after infection. This potential association of infection and suicide could have dramatic public health implications in the field of suicide prevention. The authors discussed that the heightened suicide rate could not just be attributed to the psychological effects of the physical illness and mentioned changes in the immune system’s function might be playing a role. They also found that the risk for getting a mental disorder was highest in the first three months after an infection.

In sum, their work found that having more infections and being ill, especially if hospitalized for a longer period of time, was associated with a heightened risk of death by suicide.

In another Danish population study, researchers collected information on hospitalizations and prescription medications in 1.1 million children born between January 1, 1995 and June 30, 2012.10 The investigators found that 4% of the group were diagnosed with mental disorders such as depression, bipolar disorder, schizophrenia, attention deficit hyperactivity disorder, and anxiety disorders. The authors noted that, “In particular, schizophrenia spectrum disorders, obsessive-compulsive disorder, personality and behavior disorders, mental retardation, autistic spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder and conduct disorder, and tic disorders were associated with the highest risks after infections.” In addition, as the number and severity of infections increased, so did the risk of mental disorders.

The interrelationship of infections, inflammation, immune dysregulation and mental illness symptoms continues to receive support in the medical literature. A good example of this interconnection is proposed as the mechanisms behind Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal infections (PANDAS) and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS).11 A streptococcal infection is the initiating agent in PANDAS while a virus, fungal or other bacterial infections are associated with PANS. Both disorders are manifested by a variety of neuropsychiatric symptoms related to immune dysfunction and autoimmune activity in the brain.

Next, let’s narrow our examination and go from multiple types of infections to looking at how tick-borne illnesses (TBIs) such as Lyme Borreliosis, Bartonellosis and other vector or tick-borne diseases fit into the picture.

There is evidence that Lyme spirochetes have mechanisms to evade and suppress individuals’ immune systems. Bartonella, another vector or suspected tick-borne associated pathogen, also appears to be associated with immunosuppressive effects.12,13

Robert Bransfield, a New Jersey psychiatrist did a retrospective chart review of 253 patients with Lyme disease (LD) seen in his private practice.14 He found that 43% had suicidal tendencies. He noted that on average it took eight years for the patient to be properly diagnosed and receive antibiotic treatment for his/her TBIs. Calculating from his findings using indirect methods, he estimated that Lyme and associated diseases may be responsible for 1,244 suicides and suicidal ideation in 414,540 people in the United States each year.

Bransfield described two patterns of behavior in those who died by suicide. In one group he saw the risk evolving over time. The individual, somewhat like Charlie at the beginning of this post, thinks about it often and somewhat plans the attempt. The other group he described as “unpredictable with no advanced planning, and these cases are often bizarre and senseless.” In my child and adolescent private psychiatry practice I’ve seen both types of suicidal behaviors in youth with TBIs.

One striking pattern that I’ve observed in my practice is the child who has an early history of some minor psychological issue, perhaps an ADHD or a mild anxiety disorder but nothing outrageous. Then suddenly, at some point there is a change. The youngster starts displaying a new onset of depression, angry outbursts, and defiant behavior, plus possibly a drop in school performance and difficulties with school attendance. There may even be an eating disorder component to their difficulties. Their negative behaviors escalate, appear somewhat unresponsive or minimally helped by psychotherapy and/or psychiatric medication intervention. It may even seem as if medication has worsened their problems. The end result of this somewhat impossible situation is three or four psychiatric hospitalizations for suicidal or homicidal thoughts or behavior, or progressive change in weight or the inability to function over the next year or two. Parents feel trapped in a nightmare with no good end in sight. It is not uncommon in my practice to discover that these youth have underlying infections, most commonly related to LD, Babesia, Bartonella, or other organisms like Streptococcal bacteria or Mycoplasma pneumoniae. Unrecognized viral components or parasites may also contribute to their psychiatric difficulties. In order to help these children recover, treatment for these stealth infections, plus some additional psychotropic medication, is often necessary.

The most robust study supporting this association of LD and increased rates of depression and suicidality was published by Brian Fallon et al. in 2021, using the excellent Danish registries from 1994-2016 to identify those who had contact with a hospital program, be it outpatient, inpatient or emergency room during this time period.15 The group consisted of almost 7 million people, 12,156 of whom had received the diagnosis of LD. Rates of mental disorders, affective (mood) disorders, suicide attempts and death by suicide were examined. In those with LD, the authors found a 28% higher incidence of mental disorders, a 42% higher rate of affective disorders, twice the likelihood to attempt suicide, and a 75% higher rate of suicide compared to people without LD (controls). Interestingly, individuals younger than age 40 appeared to exhibit higher rates of mental disorders after the LD diagnosis than older people. Individuals who went on to have additional episodes of LD had an increased incidence rate ratio for mental disorders, mood disorders and suicide attempts. Having more than one episode of LD did not increase the risk for incidence ratio for suicide.

In this study, the authors acknowledged that their results may not be applicable to those with LD who did not have hospital contact or those who received treatment locally and perhaps had milder depressive episodes. Another possibility is that since those who had mental illness prior to the diagnosis of their Lyme infection were excluded, it may actually be that psychiatric symptoms were actually the initial presenting symptoms of their LD.

What has all of this got to do with kids, LD and suicidality?

Sadly, not much research has been done directly on youth with TBIs and suicidality. But there are some hints. Tager et al. conducted a study looking at cognitive issues in 20 youth with chronic Lyme compared to a control group.17 As part of the study, parents and the study child completed questionnaires. What was interesting is that parents’ responses indicated that 41% (7/17) of the youth had had suicidal thoughts and 11% (2/18) made a suicidal gesture. On child rating forms (Child Depression Inventory) 40% (8/20) admitted to having had suicidal thoughts. In sum, suicidal ideation occurred in approximately 40% of the LD infected youth.

Review of the data from the large Danish study by Fallon et al. previously referenced provides some provocative insight into the risk of mental illness in youth diagnosed with TBIs.15 The data illustrated that LD infected individuals aged 19 and younger had significantly higher rates of neuropsychiatric disorders than those without LD infection. Further, those diagnosed with LD (vs. not) between the ages of 10-19 experienced similar or even higher risk for affective disorders than adults with LD infections. Extremely disturbing is the fact that individuals diagnosed with LD before age 10 had four times higher rates of suicidal behavior than those without LD.

The authors noted that most US cases are caused by the genospecies Borrelia burgdorferi (Bb), while the common European genospecies are B. afzelli and B. garinii. Borrelia burgdorferi is associated with a stronger inflammatory response than the other genospecies, and inflammation has been implicated in both depression and bipolar disorder. These data suggest that the rates of mental disorders observed in their report may be an underestimate of rates of those diagnosed with LD in the United States.

In 2017 I published a retrospective chart review of 69 child and adolescent psychiatric patients from my private N.J. practice.17 Results indicated that 71% had new findings of tick-borne pathogen exposure.

Also in 2017, I performed a retrospective chart review of 27 pediatric patients who met the DSM-IV-TR criteria for bipolar disorder, 74% were diagnosed as having one or more tick-borne disorders including LD, Bartonellosis and/or Babesiosis based on serological and clinical assessment.18 The fact that more than 70% of the youth in both studies were positive for TBIs is disturbing.

Having bipolar disorder conveys the highest rate of suicide of all psychiatric diagnoses. Estimates indicate that the rate is approximately 20-30 times that of the general population.19 This link between LD and bipolar disorder may also play a role in the increasing the risk for suicide attempts and suicide.

It is important however to apply caution when attempting to extrapolate findings from the last two studies citied. These patients lived in or near New Jersey which is known as a Lyme endemic area. Results may not generalize to youth seen in psychiatric practices in other parts of the country.

Developing a greater understanding of the relationship between LD, infection and mental illness in children is clinically important for several reasons. First, rates of mental illness in US youth are rising concomitantly with escalation in the number of cases of LD and other TBIs. Second, individuals age 19 years and younger make up 25% of the cases of LD in the United States. The most recent statistics indicate that there are an estimated 476,000 new cases diagnosed each year.3 This translates into 119,000 youth being affected annually. Many consider the number of cases to be an underestimate of the real number of cases. Third, the developing brain may be especially vulnerable to the neurological effects of TBIs. Finally, LD may also create a gene-environmental interaction in children and adolescents genetically predisposed to mental illness.

Another tick-borne bacterial infection that is at least anecdotally associated with agitation, treatment resistant depression and suicidal thoughts in infected individuals is Bartonellosis.20,21 According to the CDC, Bartonella can be transmitted to a host via bites and contact with feces from multiple vectors including cats, body lice, sand flies and fleas. Breitschwerdt et al. did a review of 17 patients diagnosed with either schizophrenia (SZ) or schizo-affective disorder (SAD) compared to 13 healthy controls looking for evidence of a Bartonella infection by using serological, microbiological and molecular methods.22 By using specialized testing called droplet digit PCR, the authors were able to differentiate between the study group and the control group. Specialized testing was positive in 11/17 or 65% for Bartonella spp. DNA in the psychiatric illness group vs. only 1/13 or 8% of the healthy controls. This initial study provided some support of the hypothesis that a Bartonella infection might be associated with the development of SZ/SAD. Greater investigation into this connection is planned.

In my clinical practice, the association between Bartonella with excessive agitation (“Bartonella rage”), impulsivity, treatment resistance to standard psychiatric medication, and self or other destructive thoughts and/or behaviors appears frequently. Currently, my observations, while enticing, can only be viewed as an impression and cannot constitute strong scientific evidence of a biologic/causal association. The relationship between Bartonella and neuropsychiatric symptoms is an important connection that requires further scientific study.

In the literature there is one report of an association of Babesiosis, a parasitic infection carried by ticks, and mental issues.23 The authors noted depression and emotional lability in kids infected with Babesia. I have and continue to see young patients with very hard to treat Babesia infections and with a treatment resistant depression or low energy state. This too is a relationship that has yet to be well studied and is ripe for future exploration.

The information discussed in this post sheds some light on the concomitant rise in mental illness in young people simultaneously while the number of kids infected by ticks is increasing. Temporal association does not necessarily mean causality.

Our kids and our future, deserve an answer to the resulting question, “To what extent does the rise in TBIs in the United States contribute to the increase in mental illness, suicide attempts and death by suicide in America’s youth?”

References

1. Clark A: Saving Charlie. A suicidal teen. A broken system. A New Jersey family’s desperate fight to save its son. Star Ledger, New Jersey. Published on Mar 06, 2022

2. www.nami.org

3. CDC.gov

4. Spiller HA, Ackerman JP, Smith GA, et al. Suicide attempts by self-poisoning in the United States among 10-25-year-old from 2000 to 2018: substances used, temporal changes and demographics.  Clin Toxicol (Phila). 2020;58(7):676-687.

5. Kõlves, K., De Leo, D. (2014). Suicide rates in children aged 10–14 years worldwide: Changes in the past two decades. British Journal of Psychiatry, 205(4), 283-285. doi:10.1192/bjp.bp.114.144402.

6. Sainsbury P, Jenkins J. S. The Accuracy of Officially Reported Suicide Statistics for Purposes of Epidemiological Research. Journal of Epidemiology and Community Health (1979-). Vol. 36, No.1 (Mar., 1982) pp. 43-48.

7. Rosenblat, JD, McIntyre RS. “Bipolar Disorder and Immune Dysfunction: Epidemiological Findings, Proposed Pathophysiology and Clinical Implications.” Brain sciences vol. 7,11 144. 30 Oct. 2017, doi:10.3390/brainsci7110144.

8. Jones BDM, Daskalakis ZJ, Carvalho AF, Strawbridge R, Young AH, Benoit HM, Ishrat Husain M. Inflammation as a treatment target in mood disorders: review. BJ Psych Open (2020) 6, e60, 1–10.

doi: 0.1192/bjo.2020.43.

9. Lund-Sørensen H, Benros ME, Madsen T, Sørensen HJ, Eaton WW, Postolache TT, Nordentoft M, Erlangsen A. A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide. JAMA Psychiatry 2016; 73(9): 912-919 doi:10.1001/jamapsychiatry.2016.1594.

10. Köhler-Forsberg O, Petersen L, Gasse C, Mortensen PB, Dalsgaard S, Yolken RH, Mors O, Benros ME. A Nationwide Study in Denmark of the Association Between Treated Infections and the Subsequent Risk of Treated Mental Disorders in Children and Adolescents.

JAMA Psychiatry 2019 March 1: 76(3):271-279 doi: 10.1001/jamapsychiatry.2018.3428.

11. Swedo SE, Frankovich J, Murphy TK. Overview of Treatment of Pediatric Acute-Onset Neuropsychiatric Syndrome. Journal of Child and Adolescent Psychopharmacology. Sept 2017. 562-565. doi: 10.1089/cap.2017.0042.

12. Gutierrez-Hoffmann MG, O’Meally RN, Cole RN, Tiniakou E, Darrah E, Soloski MJ. Borrelia burgdorferi-induced Changes in the Class II Self Immunopeptidome Displayed on HLA-DR Molecules Expressed by Dendritic Cells Front Med., 16 September 2020 http://doi.org/10.3389/fmed.2020.00568.

13. Lysakowska ME, Szybka M, Brzezińska O, Moskwa S, Konieczka M, Makowska J, Pastuszak-Lewandoska. D Cytokine and LL-37 gene expression levels in Bartonella spp. Seropositive and seronegative patients of a rheumatology clinic Adv Med Sci 2022 March 10; 67(1): 163-169 PMID: 35279619 doi: 10.1016/j.advms.2022.02.007.

14. Bransfield RC. Aggressiveness, violence, homicidality, homicide, and Lyme disease. Neuropsychiatr Dis Treat. 2018;14:693–713.

15. Fallon BA, Madsen T, Erlangsen A, Benros M. Lyme Borreliosis and Associations with Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Am J Psychiatry 2021 Oct 1; 178(10): 921-931 doi: 10.1176/appi.ajp. 2021.20091347. Epub 2021 July 28.

16. Tager FA, Fallon B. A Controlled Study of Cognitive Deficits in Children with Chronic Lyme Disease February 2001 The Journal of Neuropsychiatry and Clinical Neurosciences 13(4):500-7. doi: 2001; 13:500-507.

17. Greenberg R. Aggressiveness, violence, homicidality, homicide, and Lyme disease. Neuropsychiatry Dis Treat 2018; 14: 1253-1254 published online 2018 May 14 doi: 10.214/NDT.S168751.

18. Greenberg R. Infections and Childhood Psychiatric Disorders: Tick-Borne Illness and Bipolar Disorder in Youth

Bipolar Disord 2017, 3:1 doi: 10.4172/2472-1077.10001.

19. Miller JN , Black DW Bipolar Disorder and Suicide: a Review

Current Psych Rep 2020 Jan 1 I8;22(2):6. doi: 10.1089/vbz.2020.2729.

20. Breitschwerdt EB, Greenberg R, Maggi RG, Mozayeni BR, Lewis A, Bradley JM. Bartonella henselae Bloodstream Infection in a Boy with Pediatric Acute-Onset Neuropsychiatric Syndrome.

J CNS Dis.Vol 11 1-8. March 2019.

21. Schaller JL, Burkland GA, Langhoff PJ Do Bartonella Infections Cause Agitation, Panic Disorder and Treatment-Resistant Depression? Medscape General Medicine Med. Gen. Med. 2007; 9(3): 54.

22. Lashnits E, Maggi R, Jarskog F, Bradley J, Breitschwerdt E, Frohlich F

Schizophrenia and Bartonella spp. Infection: A Pilot Case-Control Study.

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23. Bryant KA, Marshall, GS. Clinical manifestations of Tick-Borne Illness in Children. Clinical and Diagnostic Laboratory Immunology, July 2000, p:523-527.


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