Immune System Blamed in OCD Etiology
Abstract
As researchers seek the etiology of obsessive-compulsive disorder (OCD), new data point to immune-system dysfunction as a potential culprit.
A study that found evidence of immune dysfunction as one likely cause of OCD was published January 31 in Comprehensive Psychiatry and headed by Leonardo Fontenelle, M.D., Ph.D., a professor of psychiatry at the Federal University of Rio de Janeiro in Brazil.
Forty adults who had had OCD for an average of 21 years, as well as 40 age- and gender-matched healthy controls, were evaluated for levels of various proteins in their blood that are part of the body’s immune system.
Compared with the controls, the subjects with OCD showed significantly elevated levels of four such proteins. Two—CCL3 and CXCL8—are cytokines, which have been implicated in conditions as diverse as Alzheimer’s, cancer, depression, and rheumatoid arthritis. The other two—sTNFR1 and sTNFR2—are receptors for a cytokine called tumor necrosis factor.
The researchers also looked to see whether any of these proteins were linked with specific OCD symptoms. They found that one of them—sTNFR1—correlated positively with the severity of hand washing.
The researchers thus suspect that these four immune-system proteins may play a role in adult OCD. Or, as they said in their paper, “Our findings…suggest a putative role for innate immunity in the pathogenesis of OCD.” And they also speculated on how this might be the case. For example, peripherally produced cytokines could access the brain via leaky regions in the blood-brain barrier, and once in the brain, might influence behavior through effects on neurotransmitters. Indeed, cytokines are capable of modulating the neurotransmitters dopamine, noradrenaline, and serotonin, and the cytokine CXCL8 is known to act on a receptor located on neurons in various regions of the brain.
Because almost half the OCD subjects had a current major depression, a condition known to be associated with a pro-inflammatory status, it could be argued that the links found between certain immune chemicals and OCD were due to depression rather than OCD per se. However, depressed and nondepressed OCD subjects did not differ in their immunologic profile.
One might also question whether the link between sTNFR1 and hand washing was due to immune activation resulting from washing-related skin abrasions. The researchers cannot rule out this possibility, they conceded. However, they did examine the OCD subjects’ hands and found no evidence of skin abrasions. They are thus inclined to believe that the increased sTNFR1 levels contributed to subjects’ contamination obsessions.
However, more “studies are required to establish whether our findings truly reflect immunologic dysfunction in obsessive-compulsive disorder or are the result of other hidden confounding factors,” Fontenelle and his team concluded.
The study was funded by the Brazilian Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, the Brazilian Fundacao de Amparo a Pesquisa do Estado de Minas Gerais, and the Brazilian Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro.
An abstract of “A Cytokine Study of Adult Patients With Obsessive-Compulsive Disorder” is posted at www.sciencedirect.com/science/article/pii/S0010440x11002409. 
