Abstract
Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive–compulsive disorder (OCD). The majority of clinical studies focus on the paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections [1]. The neuroimmune hypothesis is supported by the evidence of response to immunomodulatory therapies in children with treatment-refractory OCD [2].
Although various immunological abnormalities have been suggested also in adults with OCD, results are still inconsistent. Indeed, while an altered activity of the immune system is supported by the findings of increased CD8+ (i.e. suppressor T lymphocytes), decreased CD4+ (helper T lymphocytes) [3], and decreased tumour necrosis factor-α and natural killer activity in OCD patients compared with healthy controls [4, 5], the measurement of pro-inflammatory cytokine interleukin-6 levels have shown no difference between OCD patients and healthy controls [5, 6]. Also, the percentage of B cells identified by the monoclonal antibody marker D8/17 have not distinguished adults with OCD from control subjects [7]. Moreover, a serological survey for neuron-specific and other autoantibodies have revealed no humoral evidence of autoimmunity involving the neuron-, organ-, and non-organ-specific antibodies assayed in OCD patients [8].
According to the literature, only few studies have investigated whether other forms of autoimmune diathesis coexist in OCD subjects. Dinn et al. reported that adult OCD patients appear to have an increased rate of immune-related diseases above and beyond that seen in other psychiatric disorders [9]. Likewise, it has been observed that OCD was 10–15-fold more common in a cohort of patients with systemic lupus erythematosus (SLE) compared with those in community-based studies of OCD [10]. Moreover, an association between OCD and multiple sclerosis has been found [11]. Finally, two old studies evaluating the thyroid function in OCD patients, suggested a possible dysregulation of the hypothalamic–pituitary–thyroid axis [12, 13]. Therefore, in clinical practice the issue of an autoimmune diathesis in OCD patients seems to be underestimated.
In the author's personal experience, recruiting 10 consecutive adult OCD patients, according to the DSM-IV criteria [14], in a mental health service of Rome, an autoimmune diathesis was observed in four of them: three of the patients were found to have an association with SLE disorder, while one patient had Grave's syndrome. Thus, conditions suggestive of a compromised immune function should be carefully considered in OCD patients.
Indeed, it is conceivable that the association between an autoimmune diathesis and a subset of OCD may have some significance in terms of reciprocal risk factor. Two hypotheses can be formulated: an altered immune function, such as an autoimmune syndrome, may represent a risk factor for developing OCD due to the prolonged immunological stress (immunological stress may compromise the blood–brain barrier and permit the influx of anti-striatal antibodies into the central nervous system). In contrast, it is conceivable that the stress deriving from the frustrating situation determined by the OCD itself, may trigger an immunological imbalance, representing a risk factor for developing an autoimmune disease.
Therefore, systematic studies of the immune function should be carried out in OCD patients to possibly identify an immunological diathesis in a subset of them.