OCD and autoimmunity


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(Updated 8/9/04)

On Site Link: PANDAS research (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection)

Dinn WM, Harris CL, McGonigal KM, Raynard RC.
Obsessive-compulsive disorder and immunocompetence.
Int J Psychiatry Med. 2001;31(3):311-20.
"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." [Abstract]

Kiessling LS, Marcotte AC, Culpepper L.
Antineuronal antibodies: tics and obsessive-compulsive symptoms.
J Dev Behav Pediatr. 1994 Dec;15(6):421-5.
"Fluorescent serum antibody determinations were used to examine whether children with obsessive-compulsive disorder (OCD) or less pervasive obsessive-compulsive symptoms (OCS) would show evidence of caudate nucleus involvement. Recent studies of OCD have documented smaller caudate nucleus volumes in adults with childhood onset than in normal controls, but not smaller putamen volumes. Thirty-eight cases were recruited from an ongoing study of childhood neurodevelopmental disorders. Nineteen samples from clinical cases had existing or previously documented OCS and attention-deficit hyperactivity disorder (ADHD) with or without concomitant tics. Nineteen additional clinical controls with ADHD, but without tics or OCS, were identified. The sera from clinical cases showed antibodies directed against caudate [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.1], putamen (OR 3.0; 95% CI 1.5 to 5.8), or both (OR 2.9; 95% CI 1.58 to 5.7) at a rate significantly higher than that of clinical controls, providing evidence of basal ganglia involvement in OCS. These preliminary data do not support a differential effect against caudate compared to putamen for these children, but suggest a more generalized central nervous system response." [Abstract]

Roy BF, Benkelfat C, Hill JL, Pierce PF, Dauphin MM, Kelly TM, Sunderland T, Weinberger DR, Breslin N.
Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection.
Biol Psychiatry. 1994 Mar 1;35(5):335-44.
"Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD." [Abstract]

Bodner SM, Morshed SA, Peterson BS.
The question of PANDAS in adults.
Biol Psychiatry. 2001 May 1;49(9):807-10.
"BACKGROUND: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a well-defined cause of obsessive-compulsive disorder in children. However, they have not been described or fully investigated in adults newly diagnosed with obsessive-compulsive disorder. METHODS: We describe an adult with onset of obsessive-compulsive disorder at 25 years of age after a severe antibiotic-responsive pharyngitis. He was evaluated with multiple psychiatric rating scales for obsessive-compulsive disorder and Tourette's syndrome, as well as with serologic assays and radiologic studies. RESULTS: In all respects except age our patient fulfilled established criteria for PANDAS. Assays for antibodies to group A beta-hematolytic streptococci, serum D8,17 lymphocytes, antistriatal (neuronal) antibodies, and anticytoskeletal antibodies all supported the hypothesis that a poststreptococcal process was active. Magnetic resonance imaging was abnormal and is described. CONCLUSIONS: The findings suggest that this patient's illness is similar to PANDAS in presentation and that poststreptococcal disease may result in adult-onset obsessive-compulsive disorder." [Abstract]

Eisen JL, Leonard HL, Swedo SE, Price LH, Zabriskie JB, Chiang SY, Karitani M, Rasmussen SA.
The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder.
Psychiatry Res. 2001 Nov 30;104(3):221-5.
"Compared with healthy control subjects, individuals with childhood-onset obsessive-compulsive disorder (OCD) have been reported to have a higher percentage of B cells that react with the monoclonal antibody D8/17, a marker for rheumatic fever. This study sought to replicate these findings in adults with OCD. Double-blind analyses of blood samples from 29 consecutive adults with primary OCD and 26 healthy control subjects were conducted to determine the percentage of B cells identified by D8/17. Using a standard criterion of > or =12% labeled B cells to denote positivity, rates of D8/17 positive individuals did not significantly differ between the OCD (58.6%) and control (42.3%) groups. Early age of onset was not a predictor of D8/17 positivity in the OCD group. The percentage of B cells identified by the monoclonal antibody marker D8/17 did not distinguish adults with OCD from control subjects, nor did it distinguish a sub-group of adults with OCD who described pre-pubertal onset of their OCD symptoms." [Abstract]

Martino D, Giovannoni G.
Antibasal ganglia antibodies and their relevance to movement disorders.
Curr Opin Neurol. 2004 Aug;17(4):425-432.
"PURPOSE OF REVIEW: Recently, autoaggressive immunological responses were included among the causative agents of basal ganglia dysfunction. Autoaggressive immune-mediated illnesses secondary to group A beta-haemolytic streptococcal infections present with motor and psychiatric symptoms, due to basal ganglia involvement. These disorders have been associated with serum antineuronal antibodies, relatively specific to human basal ganglia tissue. This review summarizes the most recent studies concerning antibasal ganglia antibodies, focusing on the associated phenotypes and the hypotheses concerning their pathogenicity. RECENT FINDINGS: The spectrum of post-streptococcal neuropsychiatric disorders associated with antibasal ganglia antibodies seems broader than previously recognized. Other than chorea, tics and obsessive-compulsive disorder, which constituted the bulk of previously described disorders associated with antibasal ganglia antibodies, post-streptococcal neuropsychiatric disturbances include a wider range of motor and behavioural abnormalities, in keeping with the multifunctional role of the basal ganglia. An encephalitis lethargica-like illness following streptococcal infection was reported, and unusual adult-onset movement disorders associated with antibasal ganglia antibodies were documented. Moreover, investigators provided preliminary evidence for a pathogenic role of autoantibodies in Sydenham's chorea, the prototypic post-streptococcal neuropsychiatric disorder. SUMMARY: Antibasal ganglia antibodies are relatively specific in identifying post-streptococcal neuropsychiatric disorders, which constitute a wider spectrum of movement disorders than previously recognized. Although their sensitivity in diagnosing Sydenham's chorea seems excellent, it is not yet possible to extrapolate this sensitivity to all the recently identified post-streptococcal neuropsychiatric disorders. The antigens targeted by these autoantibodies and their pathogenic importance are currently under investigation. Preliminary evidence suggests that antibasal ganglia antibodies may be pathogenic." [Abstract]

Murphy TK, Petitto JM, Voeller KK, Goodman WK.
Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function?
Semin Clin Neuropsychiatry. 2001 Oct;6(4):266-76.
"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." [Abstract]

Trifiletti RR, Packard AM.
Immune mechanisms in pediatric neuropsychiatric disorders. Tourette's syndrome, OCD, and PANDAS.
Child Adolesc Psychiatr Clin N Am. 1999 Oct;8(4):767-75.
"The authors have reviewed recent data supporting the presence of immune abnormalities in several neuropsychiatric disorders (TS, OCD, and PANDAS). Several groups agree that there is a subset of patients with TS and OCD (perhaps about 10%) for whom there is a clear streptococcal trigger, validating the PANDAS concept. Also, evidence of biochemical markers for TS and OCD have begun to emerge, namely D8/17 and antibrain antibodies, which suggest the presence of similar immune abnormalities, even in idiopathic cases. If this line of research reveals definable, and relatively specific, immune abnormalities in at least some cases of TS and OCD, it will likely have important implications for the diagnosis and treatment of these common neuropsychiatric disorders, particularly in children who respond poorly to conventional therapies. Child psychiatrists are encouraged to stay tuned." [Abstract]

Zai G, Bezchlibnyk YB, Richter MA, Arnold P, Burroughs E, Barr CL, Kennedy JL.
Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder.
Am J Med Genet. 2004 Aug 15;129B(1):64-8.
"Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted." [Abstract]

Denys D, Fluitman S, Kavelaars A, Heijnen C, Westenberg H.
Decreased TNF-alpha and NK activity in obsessive-compulsive disorder.
Psychoneuroendocrinology. 2004 Aug;29(7):945-52.
"BACKGROUND: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls. RESULTS: In OCD patients, we found a significant decrease in production of TNF-alpha (p < 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003). CONCLUSIONS: Changes in TNF-alpha and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder." [Abstract]

Monteleone P, Catapano F, Fabrazzo M, Tortorella A, Maj M.
Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive-compulsive disorder.
Neuropsychobiology. 1998;37(4):182-5.
"To investigate immune system function in obsessive-compulsive disorder (OCD) we measured plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) in 14 drug-free obsessive-compulsive patients and 14 matched healthy controls. No significant differences were observed between patients and controls in plasma levels of IL-1 beta and IL-6, whereas plasma levels of TNF-alpha were significantly lower (p = 0.001) in the former. Blood levels of prolactin did not differ between the two groups, whereas plasma cortisol concentrations were significantly higher in patients than in healthy subjects (p = 0.02). No significant correlation was found between immune parameters, on the one hand, and endocrine or psychopathological measures on the other. These results suggest that OCD is associated with a decreased production in TNF-alpha, but normal synthesis of IL-1 beta and IL-6." [Abstract]

Brambilla F, Perna G, Bellodi L, Arancio C, Bertani A, Perini G, Carraro C, Gava F.
Plasma interleukin-1 beta and tumor necrosis factor concentrations in obsessive-compulsive disorders.
Biol Psychiatry. 1997 Dec 1;42(11):976-81.
"Plasma interleukin-1 beta (Il-1 beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured twice, at a 48-hour interval, in 27 drug-free obsessive-compulsive patients (12 women and 15 men) and in 27 sex-age-matched healthy controls. Il-1 beta and TNF-alpha concentrations were significantly lower in patients than in controls, whereas there were no differences in either group between men and women, between the samples of the two days, or, in the patients, between those who had and those who had not been previously treated with psychopharmacologic drugs." [Abstract]

Ravindran AV, Griffiths J, Merali Z, Anisman H.
Circulating lymphocyte subsets in obsessive compulsive disorder, major depression and normal controls.
J Affect Disord. 1999 Jan-Mar;52(1-3):1-10.
"BACKGROUND: Obsessive compulsive disorder (OCD) shares several features with depressive illness (e.g., comorbidity, early escape from dexamethasone suppression, effectiveness of serotonergic pharmacotherapy). It was of interest to establish whether OCD, like major depression, was also associated with immune alterations, notably elevations of circulating natural killer (NK) cells. METHOD: Circulating lymphocytes were determined from morning blood samples taken from OCD and major depressive patients, as well as from age- and sex-matched controls. Stress perception and coping styles were evaluated in order to assess whether such variables accompanied the NK alterations. Finally, in a subset of patients, symptoms of the illness, stress/coping, and circulating lymphocytes, were also evaluated following 12 weeks of antidepressant medication (serotonergic reuptake inhibitor). RESULTS: The major depressive and OCD patients reported increased perception of day-to-day stresses, coupled with reliance on emotion focused coping styles. Moreover, circulating NK cells were elevated among male OCD and major depressive patients, whereas only a modest increase of NK cells was seen in female major depressives. Twelve weeks of medication alleviated depressive and OCD symptoms, and resulted in normalization of NK cells in the major depressives. However, in OCD patients the reduction of symptoms was not accompanied by significant variations of circulating NK cells. CONCLUSIONS: Although major depression and OCD are both accompanied by elevated circulating NK cells, at least in males, normalization of NK cells following treatment was only evident in depression. The persistent elevations of NK cells among male OCD patients may reflect either a trait characteristic of the illness, or symptom reduction and not true remission. LIMITATIONS: Although elevations of lymphocyte subsets in major depressive and OCD patients were observed, conclusions concerning immune status in OCD ought to be held in abeyance pending assessment of other indices of immune and cytokine functioning." [Abstract]

Maes M, Meltzer HY, Bosmans E.
Psychoimmune investigation in obsessive-compulsive disorder: assays of plasma transferrin, IL-2 and IL-6 receptor, and IL-1 beta and IL-6 concentrations.
Neuropsychobiology. 1994;30(2-3):57-60.
"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." [Abstract]

Carpenter LL, Heninger GR, McDougle CJ, Tyrka AR, Epperson CN, Price LH.
Cerebrospinal fluid interleukin-6 in obsessive-compulsive disorder and trichotillomania.
Psychiatry Res. 2002 Nov 15;112(3):257-62.
"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." [Abstract]

Black JL, Lamke GT, Walikonis JE.
Serologic survey of adult patients with obsessive-compulsive disorder for neuron-specific and other autoantibodies.
Psychiatry Res. 1998 Dec 14;81(3):371-80.
"A subset of patients with pediatric onset obsessive-compulsive disorder (OCD) and tic syndromes (e.g. Tourette's syndrome) have symptom onset or exacerbation associated with infection. Some of these patients have been demonstrated to have antineuronal antibodies reactive with nuclei of the basal ganglion. It has been hypothesized that these patients have an immune process initiated by infection that affects the basal ganglion and causes obsessive-compulsive symptoms. The term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) has been coined to describe those patients with evidence of recent group A beta hemolytic streptococcal infection. We tested the serum from 13 adult patients with obsessive-compulsive disorder for panels of autoantibodies that serve as markers of autoimmunity in the practice of neurology and internal medicine. We investigated the frequency of neuron-specific autoantibodies [N-type and P/Q-type voltage-gated calcium channel antibodies, type 1 Purkinje cell antibodies, types 1 and 2 antineuronal nuclear antibodies, amphiphysin antibodies, and glutamic acid decarboxylase (65 kDa) antibodies], other organ-specific autoantibodies (muscle acetylcholine receptor-binding antibodies, striated muscle antibodies, thyroid microsomal and thyroglobulin antibodies), and non-organ-specific autoantibodies (antinuclear antibodies, antimitochondrial antibodies, and smooth muscle antibodies) to determine if any of these antibodies might serve as a serological marker for adult OCD or yield evidence of an autoimmune diathesis. Although most of our subjects had onset of OCD before 19 years of age (N=8) or before puberty (N=4), the study revealed no humoral evidence of autoimmunity involving the neuron-, organ-, and non-organ-specific antibodies that we assayed." [Abstract]


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Recent Obsessive-Compulsive Autoimmunity Research

1) Dale RC, Brilot F
Autoimmune Basal Ganglia Disorders.
J Child Neurol. 2012 Jul 25;
The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. [PubMed Citation] [Order full text from Infotrieve]

2) Taub AH, Hogri R, Magal A, Mintz M, Shacham-Diamand Y
Bioactive anti-inflammatory coating for chronic neural electrodes.
J Biomed Mater Res A. 2012 Jul;100(7):1854-8.
Chronic electrodes are widely used for brain degenerative and psychiatric daises such as Parkinson's diseases, major depression, and obsessive-compulsive disorder, and for neuronal prosthesis. Brain immune reaction to electrodes in the form of glial scar encapsulates the electrode and reduces the efficacy of deep brain stimulation and neuronal prosthesis. State-of-the-art strategies for improving brain-electrode interface use passive protein coating to "camouflage" the electrode from the immune system. In this study, we actively reduced the brain immune reaction to the chronic electrodes using immune suppressing protein, that is, interleukin (IL)-1 receptor antagonist. IL-1 receptor antagonist-coated electrodes and noncoated electrodes were chronically implanted in rats. An additional group of rats was chronically implanted with IL-1 receptor antagonist- and laminin-coated electrodes (as passive protein). Examination of glial scaring 1ne and 4 weeks after implantation indicated a significant reduction in the amount of glial scar in the vicinity of the IL-1 receptor antagonist-coated electrode in comparison to both noncoated electrode and laminin-coated electrodes. The results strongly suggest that active immune suppressing protein reduces the level of immune reaction to chronic electrodes already after 1 week after implantation and generates less immune reaction then passive protein coating. [PubMed Citation] [Order full text from Infotrieve]

3) Gray SM, Bloch MH
Systematic review of proinflammatory cytokines in obsessive-compulsive disorder.
Curr Psychiatry Rep. 2012 Jun;14(3):220-8.
Several studies have examined levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-?, interleukin (IL)-1?, and IL-6. This meta-analysis was conducted to examine the association between obsessive-compulsive disorder (OCD) and plasma serum levels of proinflammatory cytokines. Twelve studies met inclusion criteria. The meta-analysis demonstrated a significant reduction in IL-1? levels in OCD. No significant difference in plasma levels of IL-6 or TNF-? was demonstrated. Stratified subgroup analysis revealed possible moderating effects of age and medication use on IL-6 levels. Studies including children on psychotropic medication had lower plasma IL-6 levels. Stratified subgroup analysis revealed a moderating effect of comorbid depression on TNF-? levels. Elevated TNF-? levels were reported in studies that included individuals with comorbid depression. Future studies examining immune function in OCD should adjust for potential confounding due to medication use and comorbid depression. Further studies assessing cerebrospinal fluid cytokine levels in OCD are also needed. [PubMed Citation] [Order full text from Infotrieve]

4) Cappi C, Muniz RK, Sampaio AS, Cordeiro Q, Brentani H, Palácios SA, Marques AH, Vallada H, Miguel EC, Guilherme L, Hounie AG
Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder.
Arq Neuropsiquiatr. 2012 Feb;70(2):87-90.
Obsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK(®) software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic ?(2) association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the role of the immune system in its pathogenesis. [PubMed Citation] [Order full text from Infotrieve]

5) Fontenelle LF, Barbosa IG, Luna JV, de Sousa LP, Abreu MN, Teixeira AL
A cytokine study of adult patients with obsessive-compulsive disorder.
Compr Psychiatry. 2012 Aug;53(6):797-804.
[PubMed Citation] [Order full text from Infotrieve]

6) Martino D, Chiarotti F, Buttiglione M, Cardona F, Creti R, Nardocci N, Orefici G, Veneselli E, Rizzo R
The relationship between group A streptococcal infections and Tourette syndrome: a study on a large service-based cohort.
Dev Med Child Neurol. 2011 Oct;53(10):951-7.
[PubMed Citation] [Order full text from Infotrieve]

7) Brunberg E, Jensen P, Isaksson A, Keeling L
Feather pecking behavior in laying hens: hypothalamic gene expression in birds performing and receiving pecks.
Poult Sci. 2011 Jun;90(6):1145-52.
Feather pecking (FP) is a welfare and economic problem in the egg production sector. Beak trimming, the current method used to reduce FP, is also criticized. The present study used gene expression to explore the biological mechanisms underlying this behavior, which could lead to a greater understanding of the cause and a tool to mitigate the problem. White Leghorn hens performing and receiving FP, as well as neutral control birds, were identified on a commercial farm. Hypothalamic RNA from 11 peckers, 10 victims, and 10 controls was hybridized onto GeneChip Chicken Genome Arrays (Affymetrix Inc., Santa Clara, CA) to compare gene expression profiles in the different groups. Eleven transcripts corresponding to 10 genes differed significantly between the 3 groups (adjusted P < 0.05). Eight of these transcripts differed in the peckers compared with the controls, 1 was upregulated in the victims compared with the controls, and 6 differed significantly in the peckers compared with the victims. Additionally, 5 transcripts showed a trend (adjusted P < 0.1) to differ in the pecker-victim comparison. Some of the products of the differently expressed genes are involved in disorders, such as intestinal inflammation and insulin resistance, which fit well with the previously proposed hypothesis that FP is an abnormal foraging behavior. Other findings may also support the proposal that FP is linked to immune mechanisms and may serve as an animal model for obsessive compulsive disorder in humans. In conclusion, this study provides a gene list that may be useful in further research on the mechanisms behind FP. [PubMed Citation] [Order full text from Infotrieve]

8) Antony JM
Grooming and growing with microglia.
Sci Signal. 2010;3(147):jc8.
Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-expressing microglia in modulating behavior, a finding that is interesting from both the pathology and developmental biology perspectives. [PubMed Citation] [Order full text from Infotrieve]

9) Murphy TK, Kurlan R, Leckman J
The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward.
J Child Adolesc Psychopharmacol. 2010 Aug;20(4):317-31.
Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas--the basal ganglia of the brain and the related cortical and thalamic sites--adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS. [PubMed Citation] [Order full text from Infotrieve]

10) Mancuso E, Faro A, Joshi G, Geller DA
Treatment of pediatric obsessive-compulsive disorder: a review.
J Child Adolesc Psychopharmacol. 2010 Aug;20(4):299-308.
Recently, research in pediatric obsessive-compulsive disorder (OCD) has expanded to include large family genetic studies, elaboration of phenotypic dimensions, description of co-morbid disorders and their moderating effects on treatment response and outcome, research on immune-based neuropsychiatric causes, randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs), randomized controlled trials of cognitive behavioral therapy (CBT), comparative treatment trials; new approaches in behavior therapy, and increased awareness of newer approaches to treatment. The purpose of this article is to review assessment and treatment strategies to include current advances in research. [PubMed Citation] [Order full text from Infotrieve]

11) Weiss D, Infante-Duarte C, Salbach-Andrae H, Burghardt R, Hamann I, Pfeiffer E, Lehmkuhl U, Ehrlich S
Preproenkephalin expression in peripheral blood mononuclear cells of acutely underweight and recovered patients with anorexia nervosa.
Neuropsychobiology. 2010 Aug;62(3):151-7.
[PubMed Citation] [Order full text from Infotrieve]

12) Bos-Veneman NG, Bijzet J, Limburg PC, Minderaa RB, Kallenberg CG, Hoekstra PJ
Cytokines and soluble adhesion molecules in children and adolescents with a tic disorder.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1390-5.
[PubMed Citation] [Order full text from Infotrieve]

13) Podsevatkin VG, Kiriukhina SV
[Possibilities of the application of antioxidants and antihypoxants in a complex therapy of obsessive conditions in different mental disorders].
Zh Nevrol Psikhiatr Im S S Korsakova. 2010;110(3):56-61.
Based on the study of 84 patients with a syndrome of persistence within obsessive-compulsive neurosis (OCN) and generalized tic disease (GTD), we found the dysfunction of humoral and cellular immune reactions with the disturbance of regulation of hypophysis-adrenal and hypophysis-thyroid systems. The complex psychopharmacological effect of mexidol, thymogen and hyperbaric oxygenation was significantly higher compared to traditional therapy (neuroleptics and benzodiazepine anxiolytics) applied to patients with OCN and GTD. [PubMed Citation] [Order full text from Infotrieve]

14) Fluitman S, Denys D, Vulink N, Schutters S, Heijnen C, Westenberg H
Lipopolysaccharide-induced cytokine production in obsessive-compulsive disorder and generalized social anxiety disorder.
Psychiatry Res. 2010 Jul 30;178(2):313-6.
The immune system is implicated in the pathophysiology of various psychiatric disorders. In anxiety disorders such as obsessive-compulsive disorder (OCD) and generalized social anxiety disorder (GSAD), immunological findings are equivocal and sparse. In this study, we investigated the lipopolysaccharide (LPS)- stimulated cytokine levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) by peripheral blood leukocytes in 26 OCD patients, 26 GSAD patients, and 52 healthy controls. We found that leukocytes of OCD patients produced less IL-6 compared with matched controls, whereas no cytokine differences were found between GSAD patients and matched controls. When both patient groups were compared, a trend toward lower IL-6 levels in OCD patients was observed. This supports the idea of immunological involvement in the pathophysiology of OCD and suggests that GSAD and OCD might be different in immunological respect. [PubMed Citation] [Order full text from Infotrieve]

15) Cleveland WL, DeLaPaz RL, Fawwaz RA, Challop RS
High-dose glycine treatment of refractory obsessive-compulsive disorder and body dysmorphic disorder in a 5-year period.
Neural Plast. 2009;2009:768398.
This paper describes an individual who was diagnosed with obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) at age 17 when education was discontinued. By age 19, he was housebound without social contacts except for parents. Adequate trials of three selective serotonin reuptake inhibitors, two with atypical neuroleptics, were ineffective. Major exacerbations following ear infections involving Group A beta-hemolytic streptococcus at ages 19 and 20 led to intravenous immune globulin therapy, which was also ineffective. At age 22, another severe exacerbation followed antibiotic treatment for H. pylori. This led to a hypothesis that postulates deficient signal transduction by the N-methyl-D-aspartate receptor (NMDAR). Treatment with glycine, an NMDAR coagonist, over 5 years led to robust reduction of OCD/BDD signs and symptoms except for partial relapses during treatment cessation. Education and social life were resumed and evidence suggests improved cognition. Our findings motivate further study of glycine treatment of OCD and BDD. [PubMed Citation] [Order full text from Infotrieve]

16) Fluitman SB, Denys DA, Heijnen CJ, Westenberg HG
Disgust affects TNF-alpha, IL-6 and noradrenalin levels in patients with obsessive-compulsive disorder.
Psychoneuroendocrinology. 2010 Jul;35(6):906-11.
Neurobiological research of obsessive-compulsive disorder (OCD) has rarely taken in account the context dependent evocation of obsessive-compulsive symptoms. To bypass this obstacle, this study investigated neurobiological parameters during a standardized disgust provocation paradigm in patients with OCD and healthy controls. Ten OCD patients and 10 healthy controls were exposed to 9 disgust related items using a standardized provocation paradigm. Catecholamines and cortisol in plasma and lipopolysaccharide (LPS) stimulated levels of TNF-alpha and IL-6 by peripheral leucocytes were assessed along with severity of obsessive-compulsive symptoms, disgust, and anxiety levels using Visual Analogue Scales prior, during and after a provocation paradigm. Noradrenalin levels increased, while LPS stimulated TNF-alpha and IL-6 by peripheral leucocytes decreased during exposure to disgust related objects in OCD patients but not in healthy controls. Cortisol levels were not affected by exposure neither in patients nor in controls, but overall cortisol levels of OCD patients were increased compared to controls. In conclusion, our data suggests that symptom provocation in OCD patients with contamination fear is accompanied by alterations in the immune and neuroendocrine systems but does not affect cortisol levels. [PubMed Citation] [Order full text from Infotrieve]

17) Kawikova I, Grady BP, Tobiasova Z, Zhang Y, Vojdani A, Katsovich L, Richmand BJ, Park TW, Bothwell AL, Leckman JF
Children with Tourette's syndrome may suffer immunoglobulin A dysgammaglobulinemia: preliminary report.
Biol Psychiatry. 2010 Apr 1;67(7):679-83.
[PubMed Citation] [Order full text from Infotrieve]

18) Steinmetz OM, Turner JE, Panzer U
Staying on top of things right from the start: the obsessive-compulsive disorder of regulatory T cells.
J Am Soc Nephrol. 2010 Jan;21(1):6-7.
[PubMed Citation] [Order full text from Infotrieve]

19) Martino D, Defazio G, Giovannoni G
The PANDAS subgroup of tic disorders and childhood-onset obsessive-compulsive disorder.
J Psychosom Res. 2009 Dec;67(6):547-57.
Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive-compulsive disorder (OCD) are still controversial issues. Most cross-sectional studies confirm a significant association between GTS and the development of an immune response against group A beta-hemolytic streptococcus (GABHS). Moreover, longitudinal retrospective studies suggest that a recent exposure to GABHS might be a risk factor for the onset of tics and obsessive-compulsive symptoms. However, further evidence from longitudinal prospective research is needed to verify whether a temporal association between GABHS infections and symptom exacerbations is a useful and reliable criterion for the diagnosis of PANDAS. In addition, preliminary results suggest that the PANDAS spectrum might be enlarged to include attention deficit/hyperactivity disorder. Although a number of immunological biomarkers have been proposed as markers of the PANDAS variant, at present, none of these has been conclusively proved useful to diagnose and monitor disease course in children with a suspicion of PANDAS. Finally, despite their empirical use in community settings, we still lack conclusive, evidence-based data regarding the usefulness of antibiotic and immunomodulatory treatments in children with PANDAS. Given the relevance of this topic for general pediatric health, additional research efforts to solve all the pending issues and the hottest points of debate are warranted. [PubMed Citation] [Order full text from Infotrieve]

20) Rotge JY, Aouizerate B, Tignol J, Bioulac B, Burbaud P, Guehl D
The glutamate-based genetic immune hypothesis in obsessive-compulsive disorder. An integrative approach from genes to symptoms.
Neuroscience. 2010 Jan 20;165(2):408-17.
Recent advances in multiple areas of research have contributed to the identification of several pathophysiological factors underlying obsessive-compulsive disorder (OCD). In particular, the glutamate transporter gene SLC1A1 has been associated with the diagnosis of OCD. Immunological and infectious studies have reported alterations of the immune system and the presence of immune complexes directed against the Borna disease virus in OCD patients. In addition, neuroimaging of OCD patients has demonstrated abnormalities in the anterior cingulate cortex, orbitofrontal cortex, thalamus, and the basal ganglia. Neuropsychological assessments have found several cognitive disruptions that have been identified in OCD, especially impairments in cognitive flexibility. Here, we attempt to bridge the gap between these remarkable findings through several previously unpredicted pathophysiological mechanisms. We propose an integrative hypothesis that indicates how genetic and environmental factors may contribute to the structural and functional alterations of cortico-subcortical circuits, leading to the characteristic cognitive disruptions underlying OCD symptoms. [PubMed Citation] [Order full text from Infotrieve]