OCD As The Result Of An Infection?


This may sound odd, if you read the title carefully. Obsessive-compulsive disorder as the result of an infection? How is that? So people with an awful dread concerning microbes and other contaminations may have developed this particular fear as the sequel to an infection with… a bacterium type? So unconsciously the infection told that little thinking guy or girl in your brain that for many long years you would have to be mortally afraid of germs?

No. Although to my ears the concept sounds very funny, the theory behind it is much more prosaic. In 1998, the group researchers around Susan Swedo presented the concept of ‘pediatric auto-immune neuropsychiatric disorders associated with streptococcal infections‘ or as an acronym PANDAS. (Thank God for abbreviations, incidentally, and you may still impress your G.P. with the real thing, if you learn it by heart.)

The main idea is that in some children with OCD, and also related disorders from the OCD spectrum, such as involuntary tics, onset of the symptoms is unusually abrupt. Coinciding with this phenomenon was an infection with a bacterial strain termed ‘group-A beta-haemolytic streptocces’ (GABHS). Now, how then would an infection lead to OCD and/or tics?

In a patient’s bodily fluid (e.g. the blood), a defense mechanism becomes active if ‘intruders’ are detected. White blood cells (plasma cells) produce s0-called antibodies, molecules with a relatively universal basic frame and a very specific (highly variable) ‘tip’. The tip makes all the difference: it is unique to an antigen (the invading enemy). The antibody binds to a spot on the intruder that is called the epitope. This way, the stranger is tagged, and can be attacked by other elements of our immune system.

Does this always work out perfectly? No. Many of us, including the writer of these words, struggled at one or another point in our lives with a so-called auto-immune disease. There are very many of those, ranging from allergies of the skin, caused by one’s own sweat (e.g. when wearing plastic gloves in a laboratory); asthma, Crohn’s disease (where one’s own bowels are under attack, and so on; here is a list of them (taken from Wikipedia, ‘autoimmune’ as the search term):

Name Accepted/suspected Hypersensitivity Autoantibody
Alopecia areata Accepted [1] [2]   T-cells
Ankylosing Spondylitis Accepted [3] [4] [5]  
Chagas disease Suspected[6]  
Chronic obstructive pulmonary disease Suspected[7][8]   anti-elastin, Abys against epithelial cells
Crohns Disease (one of two types of idiopathic inflammatory bowel disease “IBD”) Accepted[9] IV  
Dermatomyositis Accepted[10]  
Diabetes mellitus type 1 Accepted[9] IV
Endometriosis Suspected[11]  
Goodpasture’s syndrome Accepted[9] II Anti-Basement Membrane Collagen Type IV Protein
Graves’ disease Accepted[9] II
Guillain-Barré syndrome (GBS) Accepted[9] IV Anti-ganglioside
Hashimoto’s thyroiditis Accepted[9] IV  
Hidradenitis suppurativa Suspected[12]  
Kawasaki disease Suspected  
IgA nephropathy Suspected  
Idiopathic thrombocytopenic purpura Accepted[9] II
Interstitial cystitis Suspected[13]  
Lupus erythematosus Accepted[9] III
Mixed Connective Tissue Disease Accepted[9]  
Morphea Suspected[14]  
Multiple Sclerosis Suspected  
Myasthenia gravis Accepted[9] II
Narcolepsy Accepted[15]  
Neuromyotonia Suspected[16]  
Pemphigus vulgaris Accepted[9] II Anti-Desmogein 3
Pernicious anaemia Accepted[17] II  
Psoriasis Accepted[18]   T-cells
Psoriatic Arthritis Accepted[19]    
Polymyositis Accepted[10]  
Primary biliary cirrhosis Accepted[20]   Anti-p62, Anti-sp100, Anti-Mitochondrial(M2)
Relapsing polychondritis Accepted[21]    
Rheumatoid arthritis Accepted[9] III Rheumatoid factor, Anti-MCV
Sarcoidosis Suspected  
Schizophrenia Suspected[22][23][24]  
Scleroderma Suspected[14]   Anti-topoisomerase
Sjögren’s syndrome Accepted[9]  
Stiff person syndrome Suspected  
Temporal arteritis (also known as “giant cell arteritis”) Accepted[9] IV  
Ulcerative Colitis (one of two types of idiopathic inflammatory bowel disease “IBD”) Accepted[9] IV  
Vasculitis Accepted[25] III
Vitiligo Suspected[26][27]  
Wegener’s granulomatosis Accepted[28]   Anti-neutrophil cytoplasmic(cANCA)

You will notice at a glance that there is no mention of PANDAS, or PANDAS and OCD. That is because this issue is still controversial, and under close scrutiny.

Autoimmunity was first defined as: the failure of our defense system, the immune machinery, to recognize certain cells or tissues as being constituent parts of our own body. Which simply means: our own matter may be falsely seen as ‘strange’, and labelled with antibodies, and subsequently attacked by other elements of the immune system. Damage is the result, and one of the disorders listed above may rear its ugly head.

Now, it is accepted that autoimmune responses are an inherent part of our immune systems (sometimes termed ‘natural autoimmunity’), normally prevented from causing disease by the phenomenon of immunological tolerance to self-antigens.

The general idea behind a probable connection between a streptococcal infection like GABHS (ab0ve) and the subsequent occurrence of OCD and/or tics is as follows:

We humans have in our brains a couple of important relay stations which are very old in an evolutionary sense, and these are called the basal ganglia. I quote the Wikipedia encyclopedia:

The basal ganglia (or basal nuclei) are a group of nuclei in the brains of vertebrates. They are situated at the base of the forebrain and strongly connected with the cerebral cortex, thalamus and other areas. The basal ganglia are associated with a variety of functions, including motor control and learning. Currently popular theories implicate the basal ganglia primarily in action selection, that is, the decision of which of several possible behaviors to execute at a given time. Experimental studies show that the basal ganglia exert an inhibitory influence on a number of motor systems, and that a release of this inhibition permits a motor system to become active. The “behavior switching” that takes place within the basal ganglia is influenced by signals from many parts of the brain, including the prefrontal cortex, which is widely believed to play a key role in executive functions.

Please take good notice of the terms ‘inhibition’  and ‘release from inhibition’. OCD has at its core an impairment in inhibition, and that is why trains of worrisome thoughts can last so long, just as the actions to quench those worries do. We can’t inhibit them. About the assumed location of those fears and worries, the obsessions, we’ll talk later. See this as an attempt to inform you about motor programs, taking action, why it’s hard for OCD patients to select another program, to be flexible. Patients are rigid.

The hypothesis of those advocating the importance of strep infections in a subset of cases of children’s OCD and tics is that the above basal ganglia are not properly recognized by our immune system that is active in fighting the GABHS bacteria. The basal ganglia are thus tagged with antigens aimed against the invading germs from outside, and then damaged by our own immune system. Thus, basal ganglia activity becomes deficit, and the processes involved in inhibition get affected. Simply put: the ‘stop signal’ that must end certain activities does not work anymore.

(Ooffhh… this is the first attempt to invade the serious stuff of science a bit. I hope you, dear reader, could at least get a grasp of this particular subject. As I wrote before, comments, criticism, questions, and applause is very, very welcome. Anonymously or not.)

Below is a picture of the place of the basal ganglia in the human brain, taken from Wikipedia. Don’t bother with the subdivision in different structures, these will certainly be mentioned again at a later time; just memorize the pink and purple stuff and its general place in the brain as a whole. The ‘cerebellum’, incidentally, is an ancient structure that has to do with fine movements; people become inebriated from alcohol precisely because the cerebellum can’t properly function anymore when one is under the influence.

Is GABHS the only candidate for an association with the occurrence of OCD and/or tics in some children?

No. The bacterial strain Toxoplasma gondii also has been implicated in the etiology (medical origin; provenance) of OCD. Also, there is some evidence for an involvement of Borna disease virus (BDV), a widespread viral type of infection in vertebrates, that mostly goes unnoticed. For detailed information, see the literature references below.

Literature related to OCD and infections

PANDAS:

Swedo, S. et al (1998): Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: description of the first 50 cases; in: Am. J. Psychiatry, 155(2): 264-271.

Bernstein, G.A. et al (2010): Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder; in: J. Child. & Adolesc. Psychopharmacol., 20(4): 333-340.

Borna disease virus:

Rotge, J.-Y. et al (2010): The glutamate-based genetic immune hypothesis in obsessive-compulsive disorder. An integrative approach from genes to symptoms; in: Neuroscience, 165(2): 408-417.

Dietrich, W.E. et al (2005): Brain potential amplitude varies as a function of Borna disease virus-specific immune complexes in obsessive-compulsive disorder; in: Biol. Psychiatry, 10(6): 515 and 519-520.

Bode, L. et al (1996): First isolation of infectious human Borna disease virus from patients with mood disorders; in: Mol. Psychiatry, 1(3): 200-212.

Toxoplasma gondii:

Minian, O. et al (20..): Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder? in: Psychiatry Res., 173 (1-2): 263-265.

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5 responses to “OCD As The Result Of An Infection?

  1. Lisa (forum name Womble)

    It is interesting you reference a study relating to obsessive compulsive disorder and Toxoplasma gondii. I have read in Open University literature (for course S320 Infectious disease) that T.gondii infection was found more commonly in those with schizpphrenia than in controls. Also I remember an article in New Scientist which described reduced anxiety in the presence of cats, in rodents infected with T.gondii. They speculated that in humans T.gondii might also reduce anxiety and increase risk taking behaviour.

    Regards,
    Lisa.

  2. Hello Lisa –

    Thank you very much for your comment. Schizophrenia can co-occur with OCD; and there is good information that both disorders share as one of their core features a lack of inhibition (hence the fast, fleeting and uncontrollable thought trains in SCZ).
    Especially your last line intrigues me: decreased anxiety and increased risk taking seem to go together well; on the other hand is decreased anxiety not the first symptom that you’d expect. I will certainly delve deeper into the matter.

    Cheers, Frank.

  3. Hi Lisa –

    your second contribution and my comment on that seem to have vanished. Don’t know the reason – the texts are still in my own archive (control panel). I’ll see what I can do, perhaps I’ll simply repost them.

    Cheers, Frank.

  4. Lisa wrote:

    2010/09/24 at 15:51
    I experience my most distressing obsessional thoughts as ‘loud’. Not loud as if spoken, but loud as if the volume control on the thought has been turned up (more intrusive). I read a little about experiments by Zeki and Ffytche (1998) suggesting that level of activity in particular brain nodes (such as V5/MT) correlates with level of consciousness. I wonder if something similar happen with obsessive thoughts. Brain imaging has shown that people with obsessive compulsive disorder have increased activity in thalamocortical loops involving the basal ganglia, cingulate gyrus and orbitofrontal cortex. I wonder if this increased activity equates with my feeling of increased consciousness (‘loudness’) of the frightening thoughts.

  5. Hi Lisa –

    that is a very apt comparison, or metaphor, of what we experience. You are right about the disbalance in the thalamocortical loops (also known as ‘cortico-striatal-thalamo-cortical or CSTC loops’, or ‘cortico-basal ganglial-thalamo-cortical or CBGTC loops’). Allow me an educated guess: your experienced ‘loudness’ could well be related to hyperactivity of the neurotransmitter glutamate, and hypo-activity of its ‘counterpart’ gamma-amino-butyric acid, or GABA. According to an impressive hypothesis of Edmund T. Rolls, the frightening OCD thoughts, that are experienced as being ‘overconscious’ and last too long (hence the rumination) are a sign of an overstable glutamatergic state, out of which we cannot switch easily; at any rate, not as easily as people without OCD. I still find it very hard to explain to a non-patient what actually we are going through.

    Oh, and thank you for introducing theoretical science here… I love those neurobiological terms, was still thinking about how to introduce them into future installments here. You broke the ice as it were…

    Cheers, Frank.

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