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.