Systemic autoimmune diseases are associated with an increased risk of obsessive-compulsive disorder: a nationwide population-based cohort study.

PURPOSE: Studies suggested autoimmunity plays a role in the etiology of obsessive-compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD. METHODS: Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41-2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07-2.54) dermatomyositis (3.25, 1.04-10.17), and Sjögren's syndrome (2.38, 1.53-3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD. CONCLUSIONS: This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders.

As prevalence of anxiety, posttraumatic stress, and obsessive compulsive disorders continue to rise worldwide, increasing focus has been placed on immune mediated theories in understanding the underlying mechanisms of these disorders. Associations between the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and these disorders have been recognized in the scientific literature, specifically in regard to cortisol levels, as well as changes in pro- and anti-inflammatory cytokines. The present commentary will systematically assess the scientific literature within the past decade in regard to the psychoneuroimmunology of anxiety, posttraumatic stress, and obsessive compulsive disorders. Understanding the mechanisms of these disorders is essential in order to determine efficacious and targeted treatment strategies, which may lead to substantial improvements in overall functioning, as well as significant decreases in societal and economic burden.

Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder.

Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive-compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood-brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. 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 using western blot. We further investigated CSF amino acid (glutamate, GABA, taurine, and glycine) levels and also examined the extent to which these levels were related to the presence of autoantibodies. 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. There was no significant difference in binding between patient and control sera except for a trend toward more bands to BG and thalamic protein corresponding to 43 kD among OCD patients compared with controls. CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls, and further multivariate analysis of variance showed that CSF glycine levels were higher in those OCD patients who had autoantibodies compared with those without. 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.

Research on psychoimmunology.

Several lines of evidence suggest a role for the immune system in the multifactorial pathogenesis of schizophrenia and other psychiatric and neurodegenerative disease. Later, the role of immune mediators like cytokines became a source of main interest related to the process on inflammation in the CSM. In this article we report the results of our research on cytokines in a different groups of psychiatric patients following their clinical symptomatology and the course of diseases. In particular, we observed a prevalent type 1 cytokine profile in acute multiple sclerosis patients, while IL-10 production predominated in stable multiple sclerosis individuals. The modifications of cytokine profiles observed in schizophrenic patients suggests that clinical improvement is associated with a reduction in the inflammatory-like situation present in those not currently under treatment. Our data on Alzheimer's disease (AD) support the role of the inflammatory process in the pathogenesis of AD and reinforce the hypothesis that the neurodegenerative processes in the AD patients are associated with an abnormal antigen-specific immune response. The activation of immune system mechanisms observed in obsessive compulsive disorders could be due to the combination of endogenous (hormonal alterations associated to the modifications in the hypothalamic-pituitary-adrenal axis) and exogenous (viral or bacterial infections) factors.

Cerebrospinal fluid interleukin-6 in obsessive-compulsive disorder and trichotillomania.

Recent studies have suggested that neuroimmune abnormalities may play an important role in the pathogenesis of obsessive-compulsive disorder (OCD) and related disorders. This study was undertaken to determine whether cerebrospinal fluid (CSF) concentrations of the proinflammatory cytokine interleukin (IL)-6 differ between OCD and trichotillomania patients and healthy control subjects. Lumbar puncture with a standardized procedure was performed on 26 patients with OCD and 9 with trichotillomania. All patients were drug-free and met DSM-IV criteria. Twenty-six age- and sex-matched healthy volunteers underwent the same procedure. CSF was assayed for IL-6 using a quantitative 'sandwich' enzyme immunoassay technique. Mean+/-S.D. CSF IL-6 levels did not differ between OCD patients (n=26) (2.4+/-1.1 pg/ml) and controls (n=26) (2.4+/-1.9 pg/ml) or between trichotillomania patients (n=9) (2.3+/-0.8 pg/ml) and their matched controls (n=14) (1.9+/-0.5 pg/ml). These findings fail to support speculation that ongoing immune activation may be causally involved in the pathogenesis of OCD or trichotillomania.

Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function?

During the last few years, an increased interest in the possibility of immune mediated pathophysiology of obsessive compulsive disorder (OCD) and related disorders has been seen. In the late 1980s, the National Institute of Mental Health reported an increase of obsessive compulsive symptoms in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCD symptoms but no chorea led to the coining of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus). This association has furthered interest in studying immune parameters in non-PANDAS OCD as well. This article will review the neuropsychiatric findings in OCD and Tourette syndrome (TS) with emphasis placed on PANDAS, and its association with SC, and a review of the existing studies that have assessed immunologic measures in patients with OCD and TS.

Obsessive-compulsive disorder and immunocompetence.

OBJECTIVE: A postinfectious, autoimmune response may be associated with the development of pediatric obsessive-compulsive disorder (OCD). According to this model, antistreptococcal antibodies cross-react with basal ganglia neurons following streptococcus infection. This autoimmune reaction disrupts a basal ganglia-thalamocortical circuit and generates obsessive-compulsive symptoms. One implication of this model is that prolonged immunologic stress may be a risk factor for OCD. That is, immunologic stress may compromise the blood-brain barrier and permit the influx of antistriatal antibodies into the central nervous system. This article explores one part of this putative relationship by investigating whether adult OCD patients, compared to members of other psychiatric groups, demonstrate a higher incidence of recurrent infections and other conditions suggestive of compromised immune function. METHOD: To test this hypothesis, we conducted a medical records review of 100 consecutive patients evaluated at a private psychiatric clinic specializing in the treatment of anxiety disorders. Sixty-five patients met diagnostic criteria for an Axis-I syndrome. Primary diagnoses included OCD, posttraumatic stress disorder, social anxiety disorder, generalized anxiety disorder, panic disorder with agoraphobia, and dysthymic disorder. Each medical record was reviewed for the presence of target syndromes or presenting symptoms suggestive of compromised immune function. RESULTS: Chart review revealed an increased rate of immune-related symptoms and syndromes among OCD patients in comparison to other anxiety and mood disorder groups. Groups did not differ significantly in the incidence of non-immune symptoms and syndromes. CONCLUSION: Adult OCD patients appear to have an increased rate of immune-related diseases above and beyond that seen in other psychiatric disorders.

MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection.

OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

Psychoimmune investigation in obsessive-compulsive disorder: assays of plasma transferrin, IL-2 and IL-6 receptor, and IL-1 beta and IL-6 concentrations.

This study was carried out to investigate the immune function in obsessive-compulsive disorder (OCD). Plasma levels of interleukin (IL)-1 beta, IL-6, soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin receptor (TfR), and baseline plasma cortisol levels were measured in 19 OCD patients and 19 normal controls. No significant differences in any of the above immune variables were found between subjects with OCD and normal controls. There was a significant positive correlation between IL-6 or sIL-6R concentrations and severity of compulsive--but not obsessive--symptoms. In subjects with OCD, there was a significant negative relationship between sIL-2R concentrations and plasma cortisol values. In subjects with OCD and in the study group as a whole, there were significant positive relationships between sIL-2R and TfR concentrations.