OCD: an autoimmune disease

An interesting study just published in the journal Cell demonstrates one mechanism by which immunological dysfunction causes obsessive-compulsive disorder (OCD). The authors show that microglia (the immune cells in the brain) when abnormal can cause compulsive behaviors in mice that correspond to OCD in humans:

"Mouse Hoxb8 mutants (with faulty microglia) show unexpected behavior manifested by compulsive grooming and hair removal, similar to behavior in humans with the obsessive-compulsive disorder spectrum disorder trichotillomania."

They then showed that transplanting normal microglia eliminated their pathological OCD behavior."Immunological dysfunctions have been associated with neuropsychiatric disorders...In this mouse, a distinct compulsive behavioral disorder is associated with mutant microglia."The author of a report on this study published in Science Now comments:

"Previous studies have implied a link between the immune system and obsessive-compulsive disorder and other neuropsychiatric conditions, Capecchi says. “Here, we say there is a direct connection.”...The results raise the possibility of treating obsessive-compulsive disorder by targeting the immune system rather than the brain."

What other evidence might there be that OCD in humans is an autoimmune disease? A paper published a year and a half ago in Neuroscience Letters shows how an immune cytokine abnormality also contributes to OCD. The authors begin by observing:

"Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands [affected persons studied in a genetic investigation]. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases...the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD."

They studied two polymorphisms of the genes for TNF-alpha and found that:

"Significant associations were observed between both polymorphisms and OCD."

The theme is carried forward in a paper more recently published in the journal Neuropsychopharmacology that reports the presence of anti-brain autoantibodies that derange excitatory neurotransmitters with OCD. The authors begin by observing:

"...serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive–compulsive disorder (OCD),...We examined this by investigating the presence of autoantibodies directed against the BG or thalamus in the serum as well as CSF of 23 OCD patients compared with 23 matched psychiatrically normal controls."

They also measured several neurotransmitters including the most abundant excitatory neurotransmitter glutamate. What did their data show?

"There was evidence of significantly more binding of CSF autoantibodies to homogenate of BG as well as to homogenate of thalamus among OCD patients compared with controls. ...CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls..."

Thus their conclusion:

"The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission."

This post would not be complete without including the recognized association of OCD with Tourette's disorder (TD). The authors of this clinically useful study published not long ago in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry linked TD and OCD in their investigation of the cytokines promoting the autoimmune attack on brain tissue:

"This study examined the potential role of cytokines, modulators of the immune system. We hypothesized that children with TD would have increased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β and IL-6, and decreased IL-2. We also explored whether comorbid [happening together] obsessive compulsive disorder (OCD) had an effect on the cytokine profile of TD patients."

They found that both TD and OCD had abnormal elevations of cytokines associated with their immune dysfunction, only those who had OCD comorbid with TD had significantly elevated IL-12.

"Findings suggest a role for IL-12 and IL-2 in TD, and that the TD+OCD subgroup may involve different neuroimmunological functions than the TD−OCD subgroup."

Their conclusion confirms both the autoimmune etiology and that each patient must be precisely evaluated and treated as in individual for their autoimmune disorder.