• Rosalie Greenberg, MD

Tick-borne Disorders and Mental Illness in Youth: An Underrecognized Connection

Updated: Jul 14

Part 1-

The beginning of the road: PANDAS, PANS and Pediatric Bipolar Disorder



There is no question that the rate of pediatric mental illness has increased in the last twenty to thirty years. This includes autism, attention-deficit hyperactivity disorder (ADHD), depression, pediatric bipolar disorder, as well as anxiety disorders. Studies indicate that half of adult mental illness begins by age 14. Successful early intervention may decrease the persistence of symptoms into adulthood which takes a significant emotional, social and economic toll on people throughout the world.

In recent decades there has been a more biologic approach to looking at potential causes of mental disorders. There is much less of the old “looking to blame” approach, be it focusing on difficult family interactions or the classic example of the “refrigerator mother” whose cold emotional distance was responsible for her child’s autism.

That is not to discount the importance of environmental experiences, such as growing up in poverty or being a victim physical or sexual abuse. The role of these factors in brain development is getting much more well-deserved attention. For example, studies indicate that significant stress can disrupt the blood brain barrier (BBB) which can have important effects on development. For decades the brain was considered an immune privileged site, which meant it was thought to be protected against the possibility of entry by foreign substances or infectious agents (e.g., bacteria, viruses, toxins etc.) In other words the BBB serves as a barrier to protect the brain.

Over time, it has become clear that a variety of factors, including environmental stress and trauma, can disrupt this protective net. This understanding has caused a reconsideration of certain elements of mental illness. A break in the BBB means alien intruders (infections) or even elements of the immune system that are not supposed to enter the brain, can get in more easily, resulting in a variety of problems in thinking, behavior and/or emotions.

One result of this more biologic approach to mental illness, is the recognition that infections such as those caused by Group A beta hemolytic streptococcal bacteria, responsible for sore throats, ear infections and pneumonia, can by way of autoimmunity in certain individuals, create a variety of new onset psychiatric symptoms. “Autoimmunity” refers to when the body’s immune system, designed to function as our private security system to keep us well, begins to attack healthy tissues. The mechanism behind this process is called “molecular mimicry.” For example, in rheumatic heart disease following an episode of acute rheumatic fever, the individual’s immune system that is created to fight against the group A streptococcus, attacks the healthy heart valve and leads to chronic heart valve problems.

In the 1990s, Dr. Susan Swedo and her colleagues at the National Institute of Mental Health, recognized that following a strep infection, some individuals developed an abrupt onset of obsessive-compulsive symptoms or a tic disorder, accompanied by a variety of other symptoms. This clinical presentation is called Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). The associated symptoms include:

  • Sudden unexplainable rage

  • Intense moodiness (emotional lability)

  • Personality changes

  • Symptoms of ADHD (i.e. hyperactivity, distractibility, inattention and/or impulsivity) that is new or suddenly worse

  • Refusal to eat or difficulty surrounding eating (often because of a fear of choking or vomiting)

  • Nervous system disorders in addition to tics, including other rapid, jerky movements

  • Age-inappropriate behaviors (such as bedtime fears/rituals, baby talk)

  • Separation anxiety (e.g. fear of sleeping alone, refusal to be in a different room than his/her parent, or school refusal)

  • Sensory Hypersensitivity (i.e. heightened sensitivity to touch, taste, smell, sound or light)

  • Noticeable decline in handwriting and/or math skills

  • Frequent daytime urination, recurrent or increased bedwetting or repeated complaints that the child still feels wet despite even overaggressive toileting

The illness is thought to be precipitated by a Group A Beta Hemolytic Streptococcal (GABHS) infection, which then leads to an inappropriate autoimmune response. Instead of the immune attack being focused on the invading bacteria, it is mistakenly directed against certain areas of the brain, such as the basal ganglia, leading to neuro-behavioral changes.

The illness is described as episodic and saw-toothed, meaning somewhat up and down. Patients may experience complete disappearance of symptoms between episodes. On the other hand, if there have been multiple recurrent episodes, it may be harder to see an episodic pattern and it begins to resemble a chronic illness.

Often there is an increased family history of autoimmune issues compared with the general population.

Comorbidity (having another disorder in addition to the primary one) is frequently seen in youth suffering from PANDAS. Dr. Swedo and her colleagues found that children suffering from PANDAS were highly comorbid for the following psychiatric disorders: 40% had ADHD, 42% had affective (mood) disorders and 32% had anxiety disorders.

In 2012, the diagnostic category of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) was proposed. Unlike PANDAS, which is attributed to a streptococcal infection, the instigating cause of this neuropsychiatric syndrome is not identified in the name. This category is comprised of other infections or insults (e.g., head trauma, toxin exposure etc.) with resultant immune dysfunction that manifest mainly as new onset of mainly psychiatric symptoms. Obsessive-compulsive disorder and certain eating behaviors are considered the primary symptoms in PANS. The criteria include:


I. Abrupt, dramatic onset of obsessive-compulsive disorder or severely restricted food intake

II. Concurrent presence of additional neuropsychiatric symptoms, with similarly severe and acute onset, from at least two of the following seven categories:

  • Anxiety

  • Emotional lability and/or depression

  • Irritability, aggression and/or severely oppositional behaviors

  • Behavioral (developmental) regression

  • Deterioration in school performance

  • Sensory or motor abnormalities

  • Somatic signs and symptoms, including sleep disturbances, daytime or nighttime wetting or frequent urination.

III. Symptoms are not better explained by a known neurologic or medical disorder, such as Sydenham chorea, systemic lupus erythematosus (SLE), Tourette’s Disorder.


As I noted in a previous blog, at least in my practice, there appears to have been a real increase in the rate of pediatric autoimmune psychiatric disorders in the past two decades. At the same time there has been a significant increase in a variety of psychiatric disorders in youth including the diagnosis of pediatric bipolar disorder (PBD) previously called manic-depressive illness.

PBD refers to a distinct period of changes in mood, energy, thought and behavior that can have a significant effect on a child’s or adolescent’s ability to function. This diagnosis, like most, is on a spectrum. A young person can experience manic episodes with or without depressive episodes (Bipolar I) or episodes of depression with only mild hypomanic episodes (not as severe as mania that don’t require psychiatric hospitalization [Bipolar II]). Other Specified or Unspecified Bipolar and Related Disorder are two other categories that are used when the full criteria for the diagnosis are not met. In the past, this was called Bipolar Disorder Not Otherwise Specified (NOS).

The symptoms required to make the diagnosis of a manic episode are the following: a clear period of abnormally elevated or irritable mood and heightened energy or activity lasting at least a week (or less if hospitalized) accompanied by three or more of the symptoms (four if only irritable).

  • Increased self-esteem or grandiosity

  • Decreased need for sleep

  • More talkative or pressured speech

  • Flight of ideas (loosely connected thoughts) or feeling like on has racing thoughts

  • Distractibility

  • Increase in goal directed activity or overall heightened motor agitation

  • Increased impulsivity that can cause

There are a number of symptoms that are shared between pediatric bipolar youth and those with PANDAS/PANS. These include:


1. Emotional lability.

2. Heightened anxiety. Affected children in either group often show an increase in separation anxiety. Often there is an increase in obsessive-compulsive types of behavior (e.g. wanting things just so, or shoes needing to be tied with equal tension and socks being of equal height before leaving the house.) Bipolar children often exhibit prominent anxiety symptoms when they are in the depressed phase.


3. An increase in impulsivity (or disinhibition). It’s not uncommon for a manic or hypomanic youngster to tell far out tales or steal something that he or she wants, lie, or show inappropriate sexualized behaviors (e.g., frequent potty talk in little ones, excessive notice of the opposite sex in a six-year-old). This inappropriate behavior can be shared by PANS youth.


4. Obsessively demanding.


5. Severe temper tantrums. Rage outbursts can be unpredictable or can be easily precipitated by a “no” response from the parent. After the outrageous, destructive tantrums the child may suddenly become very sad and guilty as he realizes that his behavior is unacceptable and he doesn’t even understand the reason(s) for his actions. These outbursts have been called “affective storms” in bipolar youth and do not seem so different from the “exorcist” type of behavior parents describe in their children with PANDAS.


6. Often abusive to family at home, yet well behaved in school. Some children struggle in both environments. Many kids with intense temper outbursts have some boundaries and partial control. It is as if they realize that if they misbehave in public they will be rejected and ostracized by others. Often it is because of good parental teaching of societal rules that the child works hardest at self-control outside the home.


7. Difficulty keeping up with schoolwork. Children with either condition may have a hard time focusing and be easily distracted. The manic bipolar child’s mind can be overwhelmed by ideas or in the depressed phase they may experience a paucity of thoughts.

8. Depression. Both groups of children may be out of control yet experience excessive guilt and self-loathing for negative behaviors. They can be too tired or too restless, with hypersomnia or insomnia. Changes in weight, appetite and loss of ability to enjoy previously liked things may occur. Depressed children from either cause may appear more rigid and demanding, harder to please and often more indecisive.


9. Highly comorbid with other psychiatric disorders especially true for ADHD. Other shared common disorders include anxiety issues, autistic spectrum disorders, learning problems and problems with math skills.


10. Sensory hypersensitivity to touch, sound, smell, taste, and/or sight.


11. Nightmares.


12. Complaints of physical ailments – headaches, stomachaches etc., are common especially on school mornings. Within both diagnostic groupings the child’s eating behavior may change and become much more limited – only certain foods are acceptable. Decision-making, remembering instructions, concentrating in school, all may become much more difficult.

13. Bipolar children and those with PANDAS/ are often very sensitive to treatment with standard psychiatric medications. Anti-depressants at doses typically used in depressed children may result in the child becoming more agitated, possibly appearing manic, more depressed or in a mixed (elevated and depressed) mood state.


14. Course of Illness. Although children with BPD often appear to have chronic difficulties, generally there is an episodic quality to their major mood episodes, similar to what can be seen in recurrent PANDAS/PANS (from saw tooth to chronic).


One clear difference between PBD and PANDAS/PANS is that PANDAS patients have neurological symptoms (e.g., tics, choreiform movements, etc.) that are not part of a mood disordered picture. On the other hand, tics are fairly common in childhood so the presence of motor or vocal tics in a child with PBD are not necessarily so unusual.

The extensive overlap of the two diagnostic groupings does raise the issue of how frequently one diagnosis masks or co-occurs with the other.

And relatively more importantly for this blog… what’s all of this have to do with tick-borne infections???

Stay tuned for Part 2

RG


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