Could You Catch Crazy: How Some Pathogenic Infections Cause Psychosis

Photo courtesy of Coping with Anxiety and Depression. Image. Everyday Health. August 27, 2015.

Photo courtesy of Coping with Anxiety and Depression. Image. Everyday Health. August 27, 2015.

When we were seven years old, my best friend Drew started retouching things. The habit began thirteen years ago on an otherwise normal morning. Drew’s mom pulled her tan suburban in front of the school, where other kids jumped out of their parents’ cars eager for another day of first grade. Drew, contrastingly, remained buckled in his seatbelt while he retouched the strap over and over. After sometime, Drew’s mother interrupted to ask him why he would not get out of the car. Through gritted teeth, he insisted that his seatbelt “didn’t feel right.” By the end of the week, Drew dragged his coat through the snow to “get the last touch”.

Drew went to bed a little boy that loved crayons, football, and math, and woke up neurotic. It was as if his brain was hijacked by an invisible force, and for years he was plagued with more bizarre symptoms. Certain sounds sent him into tantrums; common words and phrases drove him to tears. As a result, his family was banned from saying and doing certain things. Drew fixated on the fabric in his clothing and the textures of objects in his home. He used his pinkies to complete tasks because his other fingers felt too sensitive. He jammed his feet against smooth floors to retouch them, muted the television during commercials, and took home fistfuls of grass to retouch after football practices. For years, no one in his family could even give him a hug. That was how uncomfortable touch made him.

Drew went to many doctors, but each one was more bewildered. One time, a psychiatrist told Drew’s family that he was only “declaring himself”. Other doctors recognized that Drew displayed many traits of Obsessive Compulsive Disorder, but none could explain the abruptness or severity. However, this was because each one overlooked a critical piece of information. Soon before he started retouching, Drew suffered several recurring Strep infections. It was not until Drew was fourteen- seven years after that strange morning- that his family finally found the explanation they were desperate for: PANDAS.

PANDAS stands for “pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections”[1]. Scientists first coined the term in a 1998 publication in the American Journal of Psychiatry. While its name is complex, the science behind the disorder is simpler to understand. PANDAS is characterized by the “childhood-onset [of] obsessive-compulsive disorder (OCD) and tic disorders” [2]. Many people associate OCD with a fear of germs, compulsive organization, or an irrational fear of death. Drew’s case is very different. He obsesses over sensations such as touch or sound. His compulsions are how he reacts to these stimuli, either by retouching or repeating certain sounds or words. The National Institute of Mental Health (NIMH) reports other symptoms associated with PANDAS including anxiety, separation anxiety, hyperactivity, sensory abnormalities, “loss of academic abilities, particularly in math and visual-spatial areas”, irritability, and “developmental regression, including temper tantrums, “baby talk” and handwriting deterioration (also related to motor symptoms)” [3].

PANDAS is associated specifically with group A β-hemolytic streptococcal infections, or GABHS infections [4]. GABHS is “the most common bacterial etiology”, and causes an estimated 15-30% of pharyngitis cases in children [5]. So, how can such common bacteria illicit such an uncommon response? According to the NIMH, the answer may lie in an evolutionary survival mechanism called molecular mimicry [6]. First proposed by scientists over 30 years ago, molecular mimicry occurs when a foreign antigen, something that elicits an immune response from the body, is structurally similar to a self-antigen, a substance normally found in the body [7]. According to the National Institute of Mental Health:

The strep bacteria is a very ancient organism which survives in its human host by hiding from the immune system as long as possible. It does this by putting molecules on its cell wall that look nearly identical to molecules found on the child’s heart, joints, skin and brain tissues. This is called “molecular mimicry” and allows the strep bacteria to evade detection for a time. However, the molecules on the strep bacteria are eventually recognized as foreign to the body and the child’s immune system reacts to them by producing antibodies. Because of the molecular mimicry, the antibodies react not only with the strep molecules, but also with the human host molecules that were mimicked [8].

The strep bacteria is known to mimic the proteins in tissue of the basal ganglia, the region of the brain associated with movement and “many neuronal pathways having emotional, motivational, associative and cognitive functions” [9,10]. This likely explains the neuropsychiatric symptoms developed by children with PANDAS.

OCD symptoms are generally treated with various types of therapy, such as Cognitive-Behavioral Therapy or exposure therapy, where the patient is repeatedly exposed to what he or she obsesses over. Doctors often prescribe a class of antidepressants called SSRIs to treat the anxiety associated with OCD. But in PANDAS-specific cases, treatment is focused on the cause as much as the symptoms. Doctors who believe a child has developed PANDAS can prescribe antibiotics such as Augmentin or Amoxicillin to treat the strep infection. IVIG (intravenous immunoglobulin) treatment has also become popular. In this procedure, immunocompromised patients intravenously receive IgG antibodies. Many patients report marked improvement, but but the procedure is nonetheless expensive and known to cause unpleasant side-effects [11].

PANDAS is controversial in the scientific and medical community, and an exact instance rate is unknown [12]. In 2012, researchers from the NIMH, Yale University, and Johns Hopkins School of Medicine published an article that modified PANDAS to PANS: Pediatric Acute-onset Neuropsychiatric Syndrome [13]. This new term kept the symptoms of PANDAS, but eliminated the specific association with strep bacteria. Interestingly, the International OCD Foundation reports that “PANDAS is not the only immune system disease that may initially cause OCD to appear suddenly. Other disorders may need to be ruled out. They include: Lyme Disease, Thyroid Disease, Celiac Disease, Lupus, Sydenham Chorea, Kawasaki’s Disease, and acute Rheumatic Fever” [14].

This begs the question: if strep can bring on OCD, what are other pathogens causing? And while PANDAS is linked specifically to adolescents, are other ages vulnerable? Numerous studies, some dating back to the 40’s, have correlated diseases like Schizophrenia, anorexia, and chronic fatigue syndrome with pathogenic infection. Recent publications have provided much stronger evidence. In October 2015, NPR published an online article discussing the research of Dr. Turhan Canli, a professor at Stonybrook University. Canli’s research focuses on the “etiology of depression” [15]. According to the NPR article:

Canli notes how certain infections of the brain — perhaps most notably Toxoplasma gondii — can result in emotional disturbances that mimic psychiatric conditions. He also notes that numerous pathogens have been associated with mental illnesses, including Borna disease virus, Epstein-Barr and certain strains of herpes, including varicella zoster, the virus that causes chickenpox and shingles [16].

The Centers for Disease Control estimate that the parasite Toxoplasma gondii infects over 60 million people in the United States alone [17]. However, T. gondii can only undergo full reproduction in a feline- it is therefore advantageous for the parasite to infect as many cats as possible [18]. It has been demonstrated that T. gondii hijacks the area of the brain in mice that controls smell to make mice attracted to the smell of feline urine [19]. A mouse infected with T. gondii will be attracted to its predator; when the feline kills the mouse it is exposed to the parasite and correspondingly infected. T. gondii can then complete reproduction in a feline host. Scientists have coined this animal suicide “fatal feline attraction” [20]. Humans experience secondary T. gondii infection by coming into contact with infected meat, contaminated soil, or feces [21]. It was originally thought that T. gondii caused no symptoms in humans. However, researchers have since linked the parasite with OCD, Parkinson’s disease, Alzheimer’s disease, suicide, bipolar disorder, and Schizophrenia [22]. Other studies showed evidence that people infected with the parasite are more likely to be involved in vehicle and workplace accidents, perhaps due to “possible impairment in psychomotor performance and/or enhanced risk-taking personality profiles” [23].

Mental illness is heinously stigmatized. For years, those suffering with mental disorders have been labeled, ostracized, and medicated. But promising studies approaching mental illness from an etiological standpoint offer hope for those suffering. Life is survival of the fittest. Bacteria and viruses were here first and- like every species- are determined to be here last. In this evolutionary race – could you catch crazy?

*Author’s note- for a detailed account of a PANDAS case, please read Beth Alison Maloney’s novel Saving Sammy: A Mothers Fight to Cure her Sons OCD”. For further information on the fascinating link between evolution and illness, read Dr. Sharon Moalem’s Survival of the Sickest.

 

References:

  1. Susan E. Swedo et al., “Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: Clinical Description of the First 50 Cases.” American Journal of Psychiatry 155, no. 2 (February 1998): 264-71.
  2. Ibid, 264.
  3. “Information about PANDAS.” National Institute of Mental Health. Accessed January 23, 2016. http://www.nimh.nih.gov/labs-at-nimh/research-areas/clinics-and-labs/pdnb/web.shtml.
  4. Choby, Beth A. “Diagnosis and Treatment of Streptococcal Pharyngitis.” American Family Physician 79, no. 5 (March 1, 2009): 383-90. Accessed January 23, 2016. http://www.aafp.org/afp/2009/0301/p383.html.
  5. Ibid.
  6. “Information about PANDAS.”
  7. Cusick, Matthew F., Jane E. Libbey, and Robert S. Fujinami. “Molecular Mimicry as a Mechanism of Autoimmune Disease.” Clinical Reviews in Allergy and Immunology 42 (November 19, 2011): 102-11.
  8. “Information about PANDAS.”
  9. Ibid.
  10. Herrero, María- Trinidad, Carlos Barcia, and Juana Mari Navarro. “Functional Anatomy of Thalamus and Basal Ganglia.” Child’s Nervous System, July 26, 2002, 286-404.
  11. Hartung, H. -P., L. Mouthon, R. Ahmed, K. B. Laupland, and S. Jolles. “Clinical Applications of Intravenous Immunoglobulins (IVIg) – beyond Immunodeficiencies and Neurology.” Clinical and Experimental Immunology 158 (August 20, 2009): 23-33.
  12. “Statistics.” PANDAS Network. Accessed February 6, 2016. http://pandasnetwork.org/understandingpandaspans/about-pandaspans/statistics/.
  13. Swedo, Susan E., James F. Leckman, and Noel R. Rose. “From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome).” Pediatrics and Therapeutics 2, no. 2 (2012): 1-8.
  14. Stewart, Evelyn, and Tanya Murphy. PANDAS Fact Sheet. Boston, MA: International OCD Foundation, 2010. Accessed January 31, 2016. https://iocdf.org/wp-content/uploads/2014/10/PANDAS-Fact-Sheet.pdf.
  15. Canli, Turhan. “Turhan Canli, Ph.D.” Stonybrook University. Accessed February 6, 2016. http://www.stonybrook.edu/commcms/psychology/faculty/faculty_bio_pages/tcanli.html.
  16. Stetka, Bret. “Could Depression Be Caused by an Infection?” Shots. Last modified October 25, 2015. Accessed February 6, 2016. http://www.npr.org/sections/health-shots/2015/10/25/451169292/could-depression-be-caused-by-an-infection.
  17. “Parasites – Toxoplasmosis (Toxoplasma Infection).” Centers for Disease Control and Prevention. Last modified 2013. Accessed February 19, 2016. http://www.cdc.gov/parasites/toxoplasmosis/gen_info/faqs.html.
  18. Webster, Joanne P., Maya Kaushik, Greg C. Bristow, and Glenn A. McConkey. “Toxoplasma Gondii Infection, from Predation to Schizophrenia: Can Animal Behaviour Help Us Understand Human Behaviour?” Journal of Experimental Biology 216, no. 1 (January 1, 2013): 99-112.
  19. Ibid.
  20. Ibid.
  21. “Parasites – Toxoplasmosis (Toxoplasma Infection).” 2013.
  22. Webster et al. 2016.
  23. Ibid.

Image References:

  1. http://images.agoramedia.com/everydayhealth/gcms/Coping-With-Anxiety-and-Depression-722×406.jpg?width=623.

Kathryn Cavanna is currently a sophomore at the George Washington University. She researches in a Molecular Neuroendocrinology lab on campus, where she studies the Amylin misfolding that occurs in Type II Diabetics. Kathryn is a Biology major and hopes to minor in statistics.

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