Plasma IL-6 levels in unmedicated, comorbidity free obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is increasingly being evaluated for a neuro-immune basis. Interleukin-6 (IL-6) is the most widely studied cytokine with a potential role in altering neurotransmission. The evidence for plasma IL-6 alterations in OCD has yielded mixed results. Psychotropic medications are known to modulate inflammatory processes and cytokine levels. METHODS: In this study, we recruited unmedicated, co-morbidity-free adult OCD patients (n = 49) and sex-matched healthy controls HC (n = 47) and compared their plasma IL-6 levels and their correlation with age at onset, duration of illness, and severity. RESULTS: IL-6 plasma level (ng/ml) in unmedicated OCD patients (1.31 ± 0.67) was significantly greater compared to HC (1.03 ± 0.47) [t = 2.33 (p = 0.02)]. The group differences persisted even after controlling for age and sex [F(1, 91) = 4.57, p = 0.035, η2 = 0.05]. Plasma IL-6 did not correlate significantly with any clinical variables. CONCLUSIONS: This study adds to the existing literature on immune alterations in OCD. Alterations in plasma IL-6 might have implications in the neurotransmitter alterations and stress-response in OCD. The current study results in unmedicated and comorbidity-free OCD patients give us a better understanding of the immune alterations in OCD. Future studies in such a population will probably help in reducing the heterogeneity of findings.

Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome.

BACKGROUND: Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study. METHODS: In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored. RESULTS: Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3-8% in the PANS cohort, 1.4-2.0-fold higher than in the age- and sex-matched U.S. POPULATION: More stringent ferritin level cut-offs than the comparison CDC dataset were used. CONCLUSION: Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association. IMPACT: Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population. Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss. Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.

Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis.

Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 years) diagnosed with mental disorders, including a relevant marker of intestinal permeability, were included. Five studies were selected, with the risk of bias assessed according to the Newcastle-Ottawa scale (NOS). Four articles were identified as strong and one as moderate, representing altogether 402 participants providing evidence on IP in children diagnosed with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). In ADHD, elevated serum zonulin levels were associated with impaired social functioning compared to controls. Children with ASD may be predisposed to impair intestinal barrier function, which may contribute to their symptoms and clinical outcome compared to controls. Children with ASD, who experience gastro-intestinal (GI) symptoms, seem to have an imbalance in their immune response. However, in children with OCD, serum zonulin levels were not significantly different compared to controls, but serum claudin-5, a transmembrane tight-junction protein, was significantly higher. A meta-analysis of mean zonulin plasma levels of patients and control groups revealed a significant difference between groups (p = 0.001), including the four studies evaluating the full spectrum of the zonulin peptide family. Therefore, further studies are required to better understand the complex role of barrier function, i.e., intestinal and blood-brain barrier, and of inflammation, to the pathophysiology in mental and neurodevelopmental disorders. This review was PROSPERO preregistered, (162208).

Associations Between Subclinical Inflammatory Markers and OCD: A Retrospective Study.

Obsessive-compulsive disorder (OCD) is characterized by unwanted, intrusive and disturbing thoughts or images that cause anxiety and repetitive behaviours or mental acts to relieve these thoughts or images. Considering controversial aetiology of OCD and growing evidence for the role of inflammation in OCD, the aim of this study was to examine the association between OCD and subclinical inflammatory markers, namely neutrophil-to-lymphocyte ratio(NLR) and platelet-to-lymphocyte ratio(PLR) in adult patients and to investigate the association between antidepressant medications and NLR, PLR. Electronic medical records(EMR) of 24,635 patients aged 18-64 were reviewed and after exclusion of comorbid psychiatric and medical diagnosis 135 EMR of OCD patients were included into final analyses and compared with the healthy control group (n=133). Blood cell counts were noted to calculate NLR and PLR. Medications of patients were gathered from all patients to calculate fluoxetine-equivalent-dose(FED) to examine the effects of antidepressants on NLR and PLR. NLR and PLR were significantly higher in OCD. Contrary to the correlation of FED with NLR, PLR was found to not correlate with FED. Hence, PLR would be considered as a robust biomarker to medication effect contrary to NLR. OCD was significantly predicted by both NLR and PLR in logistic regression analyzes.

Serum zonulin and claudin-5 levels in children with obsessive-compulsive disorder.

Background: Obsessive-compulsive disorder (OCD), a chronically debilitating neuropsychiatric disorder, is characterized by distinctive and recurrent obsessions and/or compulsions. An increasing number of evidence indicates that sophisticated interactions between different neurobiological factors play a part in OCD etiology, but the certain underlying mechanisms are still mainly unknown. The present research aimed to explore whether the concentrations of serum zonulin and claudin-5 vary between OCD patients and healthy controls. The present research also intended to explore whether there is an association between zonulin and claudin-5 concentrations and OCD severity.Methods: Twenty-four (13 boys and 11 girls) OCD patients and 24 (13 boys and 11 girls) healthy controls were included in this study. The clinical severity of the OCD symptoms was evaluated by the Children's Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. Participants also filled out the Revised Child Anxiety and Depression Scales-Child Version to determine the anxiety and depression levels of the children. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured.Results: Serum claudin-5 levels were found to be significantly higher in OCD patient whereas serum zonulin levels were not significantly different between the groups.Conclusions: Taken together with our results, our study suggests that dysregulation of the blood-brain barrier, especially claudin-5, may be involved in the etiology of OCD.

Effect of Escitalopram on Serum GDNF and BDNF Levels and 5-HT Level of Brain Tissue of Obsessive-Compulsive Disorder Rats.

The present study aims to discuss the effect of escitalopram in glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) levels, and 5-Hydroxytryptamine (5-HT) in obsessive-compulsive disorder rats. A total of 42 rats were divided into three groups randomly: control group (n = 14), model group (n = 14) (obsessive-compulsive disorder group), and escitalopram group (n = 14) (model + obsessive-compulsive disorder group + escitalopram treatment). The open-field method was used to test the rat behavior, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum GDNF and BDNF levels. In addition, Western blot was used to determine the brain tissue protein levels of GDNF and BDNF and high-performance liquid chromatography + electrochemistry method to determine the 5-HT level of brain tissue. Visiting place was changed, rotational frequency and fixed duration enhanced in escitalopram group compared to model group (P < 0.05). Besides, GDNF and BDNF levels of serum and brain tissue were decreased in model group and escitalopram group compared to control group (P < 0.05), while GDNF and BDNF levels of serum and brain tissue were increased in escitalopram group compared to model group (P < 0.05). Moreover, the 5-HT level of brain tissue in escitalopram group was higher than that in model group (P < 0.05). Escitalopram could increase GDNF and BDNF levels and 5-HT content in serum and brain tissue in obsessive-compulsive disorder rats, which contributes to a function on the treatment of obsessive-compulsive disorder.

Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms.

OBJECTIVE: This retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). METHODS: In an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as "Improved/Resolved" (n = 34) or "Not-Improved/Worsened" (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability. RESULTS: Comparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10-6) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays. CONCLUSION: This study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.

Relationship between obsessive compulsive disorder and cortisol: Systematic review and meta-analysis.

Altered stress response and consequent elevated levels of circulating glucocorticoids have been found in neuropsychiatric disorders such as depression or anxiety disorders and proposed to also play a role in the pathophysiology of obsessive-compulsive disorder (OCD). Despite the observation that stressful events may precede the disease onset or even exacerbate its symptoms, studies in this field do not always report consistent results regarding the cortisol profile of OCD patients. As such, a systematic review and meta-analysis was developed to clarify this issue. This systematic review and meta-analysis was elaborated according to the PRISMA method. The analytical procedures were implemented using Metafor package in R software. Nineteen studies were included in the systematic review and 18 were included in the meta-analysis. The meta-analytic results demonstrated that OCD patients had significantly higher cortisol levels compared to controls (d = 0.76, SE = 0.146, p < 0.001). For studies using the average of multiple assessments, the standardized coefficient was significantly higher when compared to studies focusing on single measurements. Both the systematic review and meta-analysis suggest that cortisol levels are significantly higher in OCD patients than healthy individuals.

Oxidative and nitrosative stress markers in obsessive-compulsive disorder: a systematic review and meta-analysis.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. Although the pathophysiology of OCD remains unknown, pathways involved in oxidative and nitrosative stress (O&NS) have been implicated. The present study aims to systematically review the literature for quantitative evidence that patients with OCD have altered measures of blood O&NS markers. METHODS: Independent random-effects meta-analyses using standardized mean differences were conducted to assess each marker separately. Additionally, data from multiple markers were pooled together in a meta-analysis for measures of oxidant activity and another for measures of antioxidant activity. RESULTS: Thirteen studies met inclusion criteria, involving 433 OCD patients and 459 controls. Eleven blood O&NS markers were eligible for independent quantitative analyses. We found that, in OCD patients, the oxidant markers 8-hydroxydeoxyguanosine and malondialdehyde, and the antioxidants glutathione peroxidase and superoxide dismutase, were significantly increased while total antioxidant status, vitamin C, and vitamin E were significantly decreased, when comparing with controls. Regarding pooled meta-analyses, we found a statistically significant increase in oxidant markers, but non-significant results regarding antioxidant markers. CONCLUSIONS: Our meta-analysis suggests that OCD patients have a systemic oxidative imbalance that is not adequately buffered by the antioxidant system. Additional studies are needed in order to support this association.

Biological and psychosocial predictors of anxiety worsening in the postpartum period: A longitudinal study.

BACKGROUND: As many as 20% of women will experience an anxiety disorder during the perinatal period. Women with pre-existing anxiety disorders are at increased risk of worsening during this time, yet little is known about its predictors. STUDY AIM: To investigate the psychosocial and biological risk factors for anxiety worsening in the postpartum in women with pre-existing anxiety disorders. METHODS: Thirty-five (n = 35) pregnant women with pre-existing DSM-5 anxiety disorders were enrolled in this prospective study investigating the psychosocial (e.g., childhood trauma, intolerance of uncertainty, depression) and biological risk factors (e.g. C-reactive protein, interleukin-6, tumor necrosis factor-α) for anxiety worsening in the postpartum period. Anxiety worsening was defined as an increase of ≥50% or greater on Hamilton Anxiety Rating Scale scores from the third trimester of pregnancy (32.94 ± 3.35 weeks) to six weeks postpartum. RESULTS: Intolerance of uncertainty, depressive symptom severity, and obsessive-compulsive disorder symptoms present in pregnancy were significant predictors of anxiety worsening in the postpartum. LIMITATIONS: Sample heterogeneity and limited sample size may affect study generalizability. CONCLUSIONS: To our knowledge, this is the first longitudinal study to investigate psychosocial and biological risk factors for anxiety worsening in the postpartum in women with pre-existing anxiety disorders. Continued research investigating these risk factors is needed to elucidate whether they differ from women experiencing new-onset anxiety disorders in the perinatal period, and those in non-puerperal groups. Identifying these risk factors can guide the development of screening measures for early and accurate symptom detection. This can lead to the implementation of appropriate interventions aimed at decreasing the risk of perinatal anxiety worsening.

The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescent obsessive-compulsive disorder: Does comorbid anxiety disorder affect inflammatory response?

Recent adult etiologic studies indicated evidence linking increased inflammatory parameters with psychiatric disorders. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are easily obtainable clinical markers of inflammation and have been found to be increased in various medical and mental disorders. In this study, we aimed to investigate the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescents with obsessive-compulsive disorder (OCD). Secondarily, the effect of comorbid anxiety disorder with OCD on the inflammatory response was investigated. Sixty drug-naïve adolescents with OCD aged 12 to 18 years were enrolled in the patient group. Twenty-three of the OCD group had comorbid anxiety disorder (AD) and 37 had no comorbidities. One hundred twenty-eight adolescents in the same age range with no psychiatric disorders were recruited as the healthy control group. The severity of OCD symptoms was evaluated using the Children's Yale-Brown Obsessive Compulsive Scale. There were statistically significant differences in the neutrophil-lymphocyte ratio, white blood cell, neutrophil, and platelet counts among the three groups, even after adjusting for age and sex. The adolescents with OCD and AD had the highest neutrophil-lymphocyte ratio and white blood cell counts. A comorbid anxiety disorder diagnosis in addition to obsessive-compulsive disorder may increase the inflammatory response.

Adiponectin and resistin in acutely ill and weight-recovered adolescent anorexia nervosa: Association with psychiatric symptoms.

Objectives: Anorexia nervosa (AN) is a chronic illness where restriction of food intake results in decreased adipose tissue. The aim of this study was to measure the concentration of adiponectin and resistin in acute and partially weight-recovered anorectic inpatients. The associations of their levels with eating disorder symptoms were also assessed.Methods: A longitudinal study was conducted on 76 adolescent patients (ANG) and 30 age-matched healthy girls (CG). Selected adipokines serum levels, as well as the severity of depressive, obsessive-compulsive and disturbed eating behaviours, were analysed in the group of anorectic patients before (accAN) and after weight gain (recAN) and compared with the CG.Results: The concentration of adiponectin in the accAN was higher than in the CG (P = 0.05) and increased in recAN (P = 0.01). Resistin concentrations were lower in accAN and recAN than in the CG (P = 0.00). A negative correlation between adiponectin and the scores in Yale-Brown Obsessive Compulsive Scale as well as positive between resistin and Beck Depression Inventory were found.Conclusions: In the acute AN, adiponectin and resistin levels are impaired and partial weight recovery fails to normalise them thus we suggest that they can be involved in the chronicity of certain symptoms. The level of adiponectin is associated with obsessive and compulsive symptoms and resistin with depressive symptoms, which indicates their potential contribution to the regulation of emotions and behaviours in AN.

Blood levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha and cognitive functions in patients with obsessive compulsive disorder.

BACKGROUND: Cognitive dysfunction and immune system disorders are two actual issues for the patients with Obsessive Compulsive Disorder (OCD). The cognitive dysfunctions have been considered to substantial part of clinical phenomenon of OCD but exploration of various etiopathogenesis of cognitive dysfunction is needed. Immune dysfuncion has been implicated to be important part of pathopysiology of OCD and different lines of evidence suggests immune abnormalities in OCD. But whether these immune changes are traits of disease or secondary to clinical burden of the disease such as cognitive dysfunctions has not been determined. Data regarding relation between the cognitive dysfunctions and immune system disorders in OCD is unsatisfied. In this study we aimed to investigate the relation of blood levels of interleukin 1-beta (IL-1ß), interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) with various neurocognitive functions in patients with OCD in comparison with its autogenous/reactive subtypes and healthy controls. Further exploration of the effects of various clinical variables on cognitive functioning in patients with OCD and additional investigation of whether the cognitive dysfunction associated with this disorder differs from or overlap with that in other anxiety disorders are needed. METHODS: Forty-two patient with OCD and 45 age, sex and educational level matched healthy control were enrolled in the study. The diagnosis of OCD was made with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Yale- Brown Obsessive-Compulsive Scale, Beck Anxiety and Depression Inventory Scales were administered. Neuropsychological test battery including Wisconsin Card Sorting Test (WCST), Trail Making Test A and B (TMT-A, TMT-B) were used for evaluation of the patients and healthy control. The plasma of interleukin-1beta (IL-1ß), interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α) of both groups were measured with ELISA kits. RESULTS: Blood levels of IL-1ß, IL-6 and TNF-α were significantly higher in patients with OCD than the healthy control. There was significant difference in IL-1ß, IL-6 but not in TNF-α between autogenous/reactive subtypes and healthy controls. TNF-α is positively correlated with TMT-A, TMT-B and Stroop Test Part 5, negatively correlated with immediate memory, verbal learning, interference effect, immediate recall, delayed recall and recognition in RAVLT. IL-1ß was positively correlated with TMT-A score. IL-6 was positively correlated with scores of TMT-A, TMT-B. IL-6 was negatively correlated with immediate memory, verbal learning, interference effect, immediate recall and delayed recall in RAVLT, positively correlated with number of perseverative error and negatively correlated with the number of categories completed in WCST. CONCLUSION: This is the first study that investigates the relation of IL- 1ß, IL-6 and TNF-α levels with cognitive functions in OCD. There may be a contribution to pathogenesis of OCD and subtypes then new choices for treatment might be developed. Moreover, uncovering the effect of cytokine blood levels on cognitive function of OCD, new data concerning etiopathogenesis and further treatment choices can be gained.

Role of sleep deprivation in the causation of postpartum obsessive-compulsive disorder.

First-onset or recurrence of obsessive-compulsive disorder (OCD) is common after childbirth. Postpartum OCD can occur alone or in combination with other psychiatric disorders such as mood and anxiety disorders. Putative etiological mechanisms involve consideration of genetic factors, alterations in the serotonin system secondary to changes in levels of gonadal hormones, rise in oxytocin, hypothalamic-pituitaryadrenal axis hyperactivity, and neuroinflammation. Sleep deprivation arising from a host of diverse factors is common after delivery in women with postpartum OCD. The author suggests that sleep deprivation may play a critical role in the etiology of postpartum OCD. Clinical and research implications of this hypothesis are discussed.

Toxoplasma gondii - obsessive -compulsive disorder relationship: is it different in children?

BACKGROUND AND AIM: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric illness. Although the etiology of OCD is still unknown, recent investigations have associated development of OCD with infectious illness. Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite that causes infection of the central nervous system. In the last decade, a lot of researches have focused on the possible relationship between exposure to T. gondii and neuropsychiatric disorders such as schizophrenia. Therefore, in this study, it was aimed to investigate a possible association between Toxoplasma infection and OCD in children and adolescents. METHODS: We selected 55 patients with OCD (aged between 7 and 16 years) and 59 healthy children and adolescents (aged between 7 and 16 years), and investigated the seropositivity rate for anti-Toxoplasma IgG antibodies by enzyme-linked immunosorbent assay. RESULTS: The seropositivity rate for anti-T. gondii IgG antibodies among OCD patients (21.82%) was found to be higher than the rate in control group (15.25%). However, the difference between the OCD group and the control group was not statistically significant (p > .05). CONCLUSION: In contrast to studies in adult patients, the results of this study do not support the relationship between T. gondii and OCD children and adolescents.

Blood-based dynamic genomic signature for obsessive-compulsive disorder.

No biologically based diagnostic criteria are in clinical use today for obsessive-compulsive disorder (OCD), schizophrenia, and major depressive disorder (MDD), which are defined with reference to Diagnostic and Statistical Manual clinical symptoms alone. However, these disorders cannot always be well distinguished on clinical grounds and may also be comorbid. A biological blood-based dynamic genomic signature that can differentiate among OCD, MDD, and schizophrenia would therefore be of great utility. This study enrolled 77 patients with OCD, 67 controls with no psychiatric illness, 39 patients with MDD, and 40 with schizophrenia. An OCD-specific gene signature was identified using blood gene expression analysis to construct a predictive model of OCD that can differentiate this disorder from healthy controls, MDD, and schizophrenia using a logistic regression algorithm. To verify that the genes selected were not derived as a result of chance, the algorithm was tested twice. First, the algorithm was used to predict the cohort with true disease/control status and second, the algorithm predicted the cohort with disease/control status randomly reassigned (null set). A six-gene panel (COPS7A, FKBP1A, FIBP, TP73-AS1, SDF4, and GOLGA8A) discriminated patients with OCD from healthy controls, MDD, and schizophrenia in the training set (with an area under the receiver-operating-characteristic curve of 0.938; accuracy, 86%; sensitivity, 88%; and specificity, 85%). Our findings indicate that a blood transcriptomic signature can distinguish OCD from healthy controls, MDD, and schizophrenia. This finding further confirms the feasibility of using dynamic blood-based genomic signatures in psychiatric disorders and may provide a useful tool for clinical staff engaged in OCD diagnosis and decision making.

Genome-wide mRNA expression analysis of peripheral blood from patients with obsessive-compulsive disorder.

The onset of obsessive-compulsive disorder (OCD) involves the interaction of heritability and environment. The aim of this study is to identify the global messenger RNA (mRNA) expressed in peripheral blood from 30 patients with OCD and 30 paired healthy controls. We generated whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) from all the subjects using microarrays. The expression of the top 10 mRNAs was verified by real-time quantitative PCR (qRT-PCR) analysis. We also performed an enrichment analysis of the gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotations of the differentially expressed mRNAs. We identified 51 mRNAs that were significantly differentially expressed between the subjects with OCD and the controls (fold change ≥1.5; false discovery rate <0.05); 45 mRNAs were down-regulated and 6 mRNAs were up-regulated. The qRT-PCR analysis of 10 selected genes showed that they were all up-regulated, which was opposite to the results obtained from the microarrays. The GO and KEGG enrichment analysis showed that ribosomal pathway was the most enriched pathway among the differentially expressed mRNAs. Our findings support the idea that altered genome expression profiles may underlie the development of OCD.

Neonatal corticosterone mitigates autoimmune neuropsychiatric disorders associated with streptococcus in mice.

Increased glucocorticoid concentrations have been shown to favor resilience towards autoimmune phenomena. Here, we addressed whether experimentally induced elevations in circulating glucocorticoids mitigate the abnormalities exhibited by an experimental model of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS). This is a pathogenic hypothesis linking repeated exposures to Group-A-beta-hemolytic streptococcus (GAS), autoantibodies targeting selected brain nuclei and neurobehavioral abnormalities. To persistently elevate glucocorticoid concentrations, we supplemented lactating SJL/J mice with corticosterone (CORT; 80 mg/L) in the drinking water. Starting in adolescence (postnatal day 28), developing offspring were exposed to four injections - at bi-weekly intervals - of a GAS homogenate and tested for behavioral, immunological, neurochemical and molecular alterations. GAS mice showed increased perseverative behavior, impaired sensorimotor gating, reduced reactivity to a serotonergic agonist and inflammatory infiltrates in the anterior diencephalon. Neonatal CORT persistently increased circulating glucocorticoids concentrations and counteracted these alterations. Additionally, neonatal CORT increased peripheral and CNS concentrations of the anti-inflammatory cytokine IL-9. Further, upstream regulator analysis of differentially expressed genes in the striatum showed that the regulatory effect of estradiol is inhibited in GAS-treated mice and activated in GAS-treated mice exposed to CORT. These data support the hypothesis that elevations in glucocorticoids may promote central immunomodulatory processes.

8-F2-isoprostane, thioredoxin and thioredoxin reductase levels in children with obsessive-compulsive disorder.

PURPOSE: Accumulating data demonstrate that oxidative stress may play a crucial role in obsessive-compulsive disorder (OCD). This study aimed to investigate the role of 8-F2-isoprostane, thioredoxin (Trx), and thioredoxin reductase (TrxR) in children with OCD. MATERIALS AND METHODS: Thirty-three drug-free children with OCD and 35 healthy controls were included in this study. The severity of OCD symptoms was assessed via the Children's Yale Brown Obsessive-Compulsive Scale. The severity of anxiety levels was determined through the Screen for Child Anxiety-Related Emotional Disorders. Plasma levels of 8-F2-isoprostane, Trx, and TrxR were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: Plasma 8-F2-isoprostane, Trx, and TrxR levels did not show any significant differences between patient and control groups. There were no significant correlations between plasma levels of these antioxidants and severity of OCD. CONCLUSIONS: Findings of this study did not support the involvement of oxidative stress in the etiology of childhood OCD.