Pathogenesis Of Obsessive-compulsive Disorder Research Articles

Integrative analysis of shared genetic pathogenesis by obsessive‑compulsive and eating disorders.

A number of common pathological features have been observed in obsessive‑compulsive disorder (OCD) and eating disorders (EDs). The present study examined the association between OCD and EDs at the genetic level in order to gain an improved understanding of the shared genetic basis of the diseases and identify novel potential risk genes for the two diseases. An integrated analysis using large‑scale disease‑gene association data and gene expression data was conducted. Disease‑gene association data were acquired from the Pathway Studio Mammalian database. Gene expression data were acquired from samples of 133 subjects, including 15 ED cases, 16 OCD cases and 102 normal controls. Genes associated with OCD and ED presented significant overlap (21genes, P=6.70x10‑34), serving roles within multiple common genetic pathways (top 10 pathway enrichment P<4.30x10‑7) that were implicated in the two diseases. A genetic network of 17genes was constructed, through which OCD and ED were observed to influence each other. Expression analysis revealed four novel common significant genes for OCD and ED (oxytocin receptor, glutamate decarboxylase 2, neuropeptide Y and glutamate ionotropic receptor kainate type subunit 3). These genes demonstrated a strong functional association with the two diseases. The results of the present study supported the presence of complex genetic associations between OCD and ED. Genes associated with one disease are worthy of further investigation as potential risk factors for the other. The findings of the present study may provide novel insights into the understanding of the pathogenesis of OCD and ED.

Relationship Between Neuroanatomical and Serotonergic Hypotheses of Obsessive-Compulsive Disorder: A Combined Functional Magnetic Resonance Imaging-Evoked Potential Study.

The so-called neuroanatomical hypothesis (with an increased activity of orbitofrontal cortex [OFC]) and the serotonergic hypothesis (with low activity in this system) have been discussed regarding the pathogenesis of obsessive-compulsive disorder (OCD) for decades. This study aimed to look for a relationship between the 2 pathogenetic concepts. Nineteen OCD patients (8 female, 11 male, mean ± SD age = 33.37 ± 11.73 years, Yale-Brown Obsessive Compulsive Scale: 21.79 ± 6.59; diagnosed by ICD-10/DSM-IV-TR) were compared to 19 matched healthy controls (8 female, 11 male, mean ± SD age = 31.63 ± 10.79 years) and investigated (2012-2014) with the loudness dependence of auditory-evoked potentials (LDAEP) as a marker of the synaptic serotonergic activity and functional magnetic resonance imaging (fMRI) during the delay discounting paradigm, inducing OFC blood-oxygen level-dependent activity in the 2 groups. There were significant correlation coefficients between LDAEP (eLORETA right side) and fMRI OFC activities (anatomic region of interest) within the delay discounting paradigm (immediate vs control) in patients with OCD (r = -0.554; P = .014). LDAEP differed between the 2 groups with larger LDAEP at Cz in OCD patients indicating low serotonergic activity (0.28 ± 0.14 vs 0.20 ± 0.10 µV/10 dB, F₂,₃₅ = 4.66, P = .016). fMRI activations of dorsolateral and medial prefrontal cortex as well as ventral striatum (functional region of interest) were different between OCD and healthy volunteers. The 2 main pathophysiologic hypotheses of OCD seem to be related to each other as measured by LDAEP and fMRI OFC activity during the delay discounting task. This could be interpreted as a further hint that low serotonergic activity induces altered OFC responsivity, which has to be treated in each patient with OCD by a serotonin agonist.

N-Acetyl Cysteine and Vitamin D Supplementation in Treatment Resistant Obsessive-compulsive Disorder Patients: A General Review.

Obsessive-compulsive Disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. This demonstrates the need for more targeted therapeutics. Recent preclinical and clinical studies have implicated the dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. Moreover, there are studies suggesting that neuroimmune abnormalities may play an important role in the pathogenesis of OCD. N-acetyl cysteine (NAC) is a safe and readily available agent that would modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. The modulation of inflammatory pathways may also play a role in the benefits seen following NAC treatment. Therefore NAC can be considered a neuroprotective agent. This paper explores the role of NAC in the treatment of OCD conditions refractory to first-line pharmacological interventions, reviewing the clinical studies published in the last decade. The possible benefit mechanisms of NAC for this disorder will be discussed, as well as the role of vitamin D supplementation, given its specific property of stimulating the formation of glutathione in the brain. Nutraceutical supplementation in treatment resistance OCD may be important not only for improving obsessive-compulsive symptomatology, but also from a psychological perspective, given its better acceptance by the patients compared to pharmacological treatment.

Role of IL-6/IL-10 ratio in the diagnosis and in the assessment of the severity of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) has a genetic and environmental pathogenesis. The immunologic changes in OCD have been proven in many studies, but those tackling cytokine in OCD are still limited. The present study aims to evaluate the diagnostic performance of IL-6, IL-10, and the IL-6/IL-10 ratio in the OCD patient group, and to show their correlation with the clinical parameters of OCD. Eighty subjects (60 OCD patients and 20 matched controls) were participating in this study. The enzyme-linked immunosorbent assay was run to quantify the IL-6 and IL-10. Serum IL-6 exhibited a higher result in OCD patients than controls (p = 0.002) but serum IL-10 levels had no significant difference (p > 0.05). IL-6/IL-10 ratio showed significantly higher values in OCD patients than controls (p < 0.0001). Serum IL-6 and IL-6/IL-10 ratio were negatively correlated with age of onset but were directly correlated with disease duration and disease severity. IL-6/IL-10 ratio showed 86.7% sensitivity and 90% specificity in OCD diagnosis. An immune activation is implicated in the OCD pathogenesis. This was confirmed by the high serum levels of IL-6 in OCD patients. IL-6/IL-10 ratio showed a considerable sensitivity and specificity in the OCD diagnosis. IL-6 and IL-6/IL-10 ratio are correlated positively with the OCD intensity.

Associations of Observed Performance Monitoring During Preschool With Obsessive-Compulsive Disorder and Anterior Cingulate Cortex Volume Over 12 Years

Monitoring one's performance is necessary for learning and adaptive behavior; however, heightened performance monitoring is a purported endophenotype of obsessive-compulsive disorder (OCD). The anterior cingulate cortex (ACC), a brain region implicated in the pathogenesis of OCD, is associated with performance monitoring. Whether performance monitoring early in development is an identifiable risk factor for OCD and whether early childhood performance monitoring is associated with later alterations in ACC volume are unknown. To determine whether an observed indicator of heightened performance monitoring during the preschool age is associated with later onset of OCD and altered dorsal ACC (dACC) volume through adolescence. This longitudinal observational cohort study was performed at an academic medical center as part of the Preschool Depression Study. A sample of 292 children oversampled for depression from September 22, 2003, through May 12, 2005, completed a performance-based observational task during which they received persistent negative evaluation. Blind raters behaviorally coded child performance monitoring. During the next 12 years, children completed annual diagnostic assessments; 133 completed the final behavioral follow-up and 152 contributed 1 to 3 magnetic resonance imaging scans. Follow-up was completed on August 14, 2017. Onset of DSM-5 diagnosis of OCD from baseline to the final behavioral assessment and whole-brain-adjusted dACC volume at the 3 waves of scanning. Among the 292 preschool children who completed the baseline evaluation (51.4% boys; mean [SD] age, 4.5 [0.8] years), when controlling for demographic and clinical indicators, those who exhibited observed heightened performance monitoring were 2 times more likely to develop OCD (n = 35) during the next 12 years (odds ratio, 2.00; 95% CI, 1.06-3.78; P = .03). Multilevel modeling of dACC volume across the 3 scan waves (n = 152) demonstrated that heightened performance monitoring was associated with smaller right dACC volume (intercept estimate, -0.14; SE, 0.07; t = -2.17; P = .03). An ecologically valid indicator of performance monitoring in early childhood was associated with onset of OCD and smaller dACC volumes in later childhood and adolescence. Early childhood observed performance monitoring is a readily observed risk factor of OCD that can be identified in preschool-aged children.

The detection of white matter alterations in obsessive-compulsive disorder revealed by TRActs Constrained by UnderLying Anatomy (TRACULA).

PurposeIn recent years, a large number of studies have investigated obsessive–compulsive disorder (OCD) using diffusion-weighted images (DWIs) and have reported microstructural abnormalities in various regions, mainly the corpus callosum and cingulum. In the present study, we aimed to detect microstructural changes in the white matter using whole-brain tractography.Patients and methodsWe obtained MRI data from 25 adult non-medicated OCD patients and 27 healthy controls. DWI data from MRI scans were analyzed by the automated probabilistic tractography method referred to as TRActs Constrained by UnderLying Anatomy (TRACULA). We investigated diffusivity parameters: fractional anisotropy, radial diffusivity (RD), axial diffusivity, and mean diffusivity in 18 major white matter tracts and examined indices to know which measurements in which fibers can predict the diagnosis of OCD.ResultsCompared to healthy controls, OCD patients had significantly increased RD in the forceps major and a reduction of RD in the right cingulum angular (infracallosal) bundle. There was no correlation between these values and the clinical features.ConclusionWe found RD alterations in the forceps major and the right cingulum angular (infracallosal) bundle, which might be associated with myelination changes in the temporal and occipital regions in OCD. Our results suggest that the pathogenesis of OCD may include abonormality of myelination status in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions.

Anterior thalamic radiation structural and metabolic changes in obsessive-compulsive disorder: A combined DTI-MRS study

Numerous studies indicate the cortico-striato-thalamo-cortical (CSTC) circuit plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD). The anterior thalamic radiation (ATR), as a major fiber in the fronto-thalamic circuitry, contributes to symptomology of OCD. However, the underlying biochemical mechanism in relation with its structural alteration remains not understood. This study investigated the structural abnormality of ATR and its correlation with thalamic metabolic alteration in OCD, using diffusion tensor image (DTI) and proton magnetic resonance spectroscopy (1H-MRS). Twenty-six unmedicated adult OCD patients and twenty-six matched healthy controls participated in DTI study. Thirteen OCD patients and thirteen healthy controls, a subset of DTI participants, took part in MRS study. The results showed that mean fiber length of right ATR negatively correlated with ipsilateral thalamic choline (Cho) level in OCD patients. Additionally, significantly higher Cho concentration was detected in right thalamus of OCD patients compared to healthy controls. Moreover, the mean fractional anisotropy (FA) value of right ATR positively correlated with patients Yale–Brown Obsessive Compulsive Scale (YBOCS) total score, as well as YBOCS compulsion score. These results suggested the coupling of structural and metabolic changes in right ATR, which might serve as a multi-modal biomarker contributing to the pathogenesis of OCD.

Cortical thickness and white matter integrity abnormalities in obsessive-compulsive disorder: A combined multimodal surface-based morphometry and tract-based spatial statistics study.

Cerebral morphological abnormalities may play a key role in pathogenesis of obsessive-compulsive disorder (OCD). However, few studies have used multimodal imaging strategies to investigate alterations of cortical morphometry and white matter (WM) integrity. This study aimed to evaluate cortical thickness, cortical and subcortical volume, and WM integrity characteristics in OCD patients comprehensively. We acquired magnetic resonance imaging (MRI) scans from 52 OCD patients and 46 well-matched healthy controls (HCs). Cortical thickness and cortical and subcortical volume were measured using the surface-based morphometry (SBM) approach. We also evaluated fractional anisotropy (FA) and mean diffusivity (MD) derived from diffusion tensor imaging (DTI) using tract-based spatial statistics (TBSS). The disease severity was evaluated by score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). For those brain regions exhibiting altered structure, correlations between alterations and clinical symptoms severity were analyzed in all patients and medication-naïve patients, respectively. Compared with controls, OCD patients exhibited cortical thinning in right posterior cingulate cortex (PCC), as well as significantly decreased FA values in the genu and body of corpus callosum (CC). In medication-naïve patients group, the total Y-BOCS score and obsession score were significantly negative correlated with right PCC cortical thickness. OCD patients demonstrated symptom-related reduced cortical thickness structural alteration of the right PCC, and altered WM integrity in the genu and body of CC. Medication seems could alleviate the alteration of cortical thickness but not WM integrity. Combined multimodal neuroimaging methods may provide a more comprehensive perspective to clarify the pathological mechanism of OCD.

Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40-60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).

NEURO-HEMODYNAMIC ENDOPHENOTYPES OF EMOTIONAL INTERFERENCE IN OCD: FMRI STUDY USING EMOTION COUNTING STROOP TASK

Background Patients with obsessive compulsive disorder (OCD) have bias toward threat-related information as evidenced through emotional interference tasks, for which fronto-striatal and fronto-limbic regions have been proposed as substrates. In this study, we sought to examine the endophenotype pattern of neuro-hemodynamic substrates of emotion counting stroop (ecStroop) paradigm in patients with OCD, their unaffected siblings [first degree relatives-FDR] and healthy controls. Methods OCD patients (medication naive)[N=16], their unaffected siblings(FDR)[N=16] and healthy controls [N=24] were compared using an established ecStroop paradigm in a 3-Tesla fMRI. The relative BOLD signals corresponding to the three types of conditions (neural words-N, words with negative emotional salience-E and words with salience for OCD-O) were examined in the apriori hypothesized brain regions with age, sex and years of education as covariates. The regions with uncorrected p Results Both in O minus N contrast (F=10.9) and O minus E contrast (F=10.5), the groups demonstrated significant differential activation of right insula (BA 13,p=0.02). The post-hoc analyses showed in patients and FDRs relative to HC the following: significant hyperactivation of insula in O minus E contrast; significant hyperactivation of right insula and right DLPFC (BA 9) in O minus N contrast. Conclusions The neuro-hemodynamic responses corresponding to the obsessive words in insula and DLPFC could be potential endophenotypes. “Threat relatedness” might thus have a vulnerability meaning in the pathogenesis and neurobiological basis of OCD.

L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study.

Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment. Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial. Patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10weeks. The Yale- Brown Obsessive Compulsive Scale (Y-BOCS) was used for assessing the severity of symptoms at baseline and at weeks 4, 8, and 10. General linear model repeated measure showed significant effects for Time×Treatment interaction on total Y-BOCS [F (2.10, 88.42)=8.66, p<0.001], obsession [F (1.88, 79.34)=4.96, p=0.01] and compulsion [F (1.88, 79.11)=4.57, p=0.01]. At week 10, the change from baseline in Y-BOCS scores was 8.86±2.89 (mean±SD) in the L-carnosine group compared to 5.86±2.88 in the placebo group. L-carnosine results in significant reduction of obsessive-compulsive symptoms when used as an adjuvant to fluvoxamine.

Associations between rumination and obsessive-compulsive symptom dimensions

In recent years there has been increased interest in understanding cognitive processes that play a role in the pathogenesis of obsessive-compulsive disorder (OCD). One cognitive factor that has received little attention is rumination. Rumination, defined as the tendency to repetitively analyze ones problems and feelings of distress, has been implicated in the development and maintenance of several mood and anxiety-related disorders. Thus, the primary aim of the current study was to examine the role of rumination in OCD symptoms using an unselected treatment-seeking sample (N=105). Multiple regression analyses revealed a significant association between rumination and the unacceptable thoughts/neutralizing domain of OCD. These findings remained significant even after accounting for a relevant and related construct, in particular negative affect. These findings support a growing body of literature establishing rumination as a transdiagnostic risk factor. Further clinical and experimental research is needed to confirm these findings and expand our knowledge of metacognitive models of OCD.

Abnormal resting-state brain activities in patients with first-episode obsessive-compulsive disorder.

ObjectiveThis paper attempts to explore the brain activity of patients with obsessive-compulsive disorder (OCD) and its correlation with the disease at resting duration in patients with first-episode OCD, providing a forceful imaging basis for clinic diagnosis and pathogenesis of OCD.MethodsTwenty-six patients with first-episode OCD and 25 healthy controls (HC group; matched for age, sex, and education level) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Statistical parametric mapping 8, data processing assistant for resting-state fMRI analysis toolkit, and resting state fMRI data analysis toolkit packages were used to process the fMRI data on Matlab 2012a platform, and the difference of regional homogeneity (ReHo) values between the OCD group and HC group was detected with independent two-sample t-test. With age as a concomitant variable, the Pearson correlation analysis was adopted to study the correlation between the disease duration and ReHo value of whole brain.ResultsCompared with HC group, the ReHo values in OCD group were decreased in brain regions, including left thalamus, right thalamus, right paracentral lobule, right postcentral gyrus, and the ReHo value was increased in the left angular gyrus region. There was a negative correlation between disease duration and ReHo value in the bilateral orbitofrontal cortex (OFC).ConclusionOCD is a multifactorial disease generally caused by abnormal activities of many brain regions at resting state. Worse brain activity of the OFC is related to the OCD duration, which provides a new insight to the pathogenesis of OCD.

OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD.

Early-onset versus late-onset obsessive–compulsive disorder: an immunological comparative study

Objectives This study was conducted to investigate the possible role of streptococcal infection in obsessive–compulsive disorder (OCD) and to clarify whether the age of onset could affect its clinical presentation and immunological results. Participants and methods The study was carried on 96 participants. They were divided into 46 OCD patients with a mean age of 30.76 years and 50 healthy controls with a mean age of 28.94 years. The patients group was subdivided according to the age of onset into the early-onset group include 21 patients with onset age of 18 years or less and the late-onset group include 25 patients with onset age above 18 years. All participants were subjected to psychometric and serological assessments of serum antibasal ganglia autoantibodies (ABGA) and antistreptolysin O titer (ASOT). Results Rates of ABGA positivity were 26.1% in the OCD group compared with 30% in the control group, with no significant difference (P=0.670). ASOT positivity were 6.5% in the OCD group, whereas none of the controls had positive ASOT (P=0.160). Positivity for ASOT and ABGA was not associated with the age of onset as 95.2 and 71.4% of the early-onset group had positive ASOT and ABGA results against 92 and 76% in the late-onset group, respectively, with no significant differences (P≥0.05) or clinical variables. Positivity for ASOT was not associated with ABGA positivity. Conclusion The negative results of this study do not exclude the role of autoimmunity in OCD pathogenesis. Further investigations are needed to establish this role.

Serum Proteomic Profiling of Obsessive-Compulsive Disorder, Washing Subtype: A Preliminary Study.

Introduction:Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD.Methods:Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile of females with washing subtype of OCD was performed. Serum samples were obtained from females with washing subtype of OCD. Following the protein extraction from the serum with acetone perception, the samples were subjected to 2DE for separation based on pI and molecular weight (MW) with triple replications. Finally, the protein spots were visualized using Coomassie blue staining method and analyzed by Progenesis SameSpots software. Furthermore, protein-protein interaction (PPI) network analysis was handled by the application of Cytoscape software.Results:The results suggested that 41 matched spots demonstrated significant expression alterations among which 5 proteins including immunoglobulin heavy constant alpha-1 (IGHA1), apolipoprotein A-4 (APOA4), haptoglobin (HP), protein α-1-antitrypsin (SERPINA1), and component 3 (C3) were identified by database query. Additionally, PPI network analysis indicated the central role of SERPINA1 and C3 in the network integrity. However, albumin (ALB), amyloid precursor protein (APP), and protein α-1-antitrypsin (APOA1) proteins were important in OCD PPI network as well. The identified proteins were related to 3 processes: acute-phase response, hydrogen peroxide catabolic process, and regulation of triglyceride metabolic process.Conclusion:It was concluded that these proteins may have a fundamental role in OCD pathogenesis. Moreover, the dysregulation of inflammatory and antioxidant systems in OCD risk was suggested by the current study. However, evaluation of bigger sample sizes and application of mass spectrometry are essential requirements to confirm this preliminary evaluation.

Hypogyrification in obsessive-compulsive disorder.

Previous studies hypothesized that neurodevelopmental risk factors may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Cortical folding has been shown to be a reliable indicator for normal and altered neurodevelopment, but in OCD it has barely been investigated up to now. The present study investigates whether alterations in gyrification are detectable in OCD and, if so, how these are associated with clinical characteristics. We compared the local Gyrification Index (lGI) between 75 OCD patients and 75 matched healthy subjects across the whole brain. In addition, for those regions exhibiting an altered lGI in patients we explored a potential relationship to symptom severity, age of onset, and influence of medication. OCD patients had a significantly decreased lGI in right parietal, precentral but also insula, temporal, pars triangularis and rostral middle frontal regions compared to healthy subjects. A positive association with age of onset was found but no association with symptom severity. There was no effect of co-morbidity or medication. The reduced gyrification found in OCD confirms previous findings in other psychiatric disorders and suggests that alterations may already occur during early stages of brain development. Our findings support the idea that altered cortical folding might represent a trait characteristic of the disorder although longitudinal studies are needed to clarify the trajectory of this morphological measure in OCD.

Neuronal nitric oxide synthase polymorphisms in obsessive-compulsive disorder

Background: Obsessive-compulsive disorder (OCD) is a mental disease characterized by recurrent and intrusive thoughts and repetitive behaviours that negatively affect the quality-of-life of the patients. Recent studies have implicated the participation of neuronal nitric oxide in OCD pathogenesis as a neurotransmitter modulator.Aims: To identify whether variations in neuronal nitric oxide synthase (nNOS) genes may render individuals susceptible to OCD development.Methods: This study examined nNOS polymorphisms in 100 OCD patients and 121 unrelated healthy controls by polymerase chain reaction and restriction enzyme digestion methods.Results: nNOS 276 C + genotype incidence was significantly higher in OCD patients than controls and conferred a 2-fold increased risk for OCD. No significant differences were observed in frequencies of nNOS 84 genotypes between patients and controls.Conclusion: This study shows an association between nNOS gene polymorphism and OCD. Exact mechanisms by which nNOS gene variants contribute to OCD pathogenesis need to be further investigated.

Magnetic Resonance Spectroscopy of Brain Circuits in Patients with First-Episode Obsessive-Compulsive Disorder

Background: Obsessive-compulsive disorder (OCD) is considered neurodevelopmental disorder that shares the feature of dysfunctional frontal-subcortical circuitry, yet the relationship between structural abnormalities or neurobiochemistrical changes and OCD pathogenesis is still unknown. Objectives: This study aims to use magnetic resonance spectroscopy (MRS) to discover substance-metabolism abnormalities of brain circuits in patients with first-episode OCD, and to study the mechanism of OCD. Patients and Methods: Twenty patients with first-episode OCD and twenty gender- and age-matched normal controls were studied. Neurochemical abnormalities, including ratios of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were measured in the prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, caudate nucleus, and thalamus with three-dimensional 1H-proton MRS (3D 1H-MRS). The data of the ratios in the two groups were analyzed with a independent samples t-test. Results: Cho/Cr ratios in the thalamus were significantly higher in the first-episode OCD patients than in the controls (P < 0.01), and the NAA/Cr ratios in the caudate nucleus and thalamus were significantly lower in the first-episode OCD patients than in the controls (P < 0.01). However, NAA/Cr ratios in the anterior cingulate cortex and orbitofrontal cortex were higher in the first-episode OCD patients than in the controls (P < 0.01). Conclusion: Distinct neurochemical and histological structure changes (cortico-striatal-thalamic-cortical cycle) exist in patients with first-episode OCD. 1H-MRS is capable of identifying these changes by assessing metabolic abnormalities.

DNA damage and antioxidants in treatment naïve children with obsessive–compulsive disorder

The current study aimed to investigate whether serum antioxidant levels and DNA damage differ between the children and adolescents with Obsessive Compulsive Disorder (OCD) and healthy controls. The study included 31 children (Male/Female, 22/9; age range 7–17 years), with treatment naïve OCD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) and 28 age- and gender-matched healthy control subjects. Children's Yale Brown Obsession Compulsion Scale (CY-BOC) was applied to the children. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all measured by the enzyme-linked immunosorbent assay method. GPx, CoQ and 8-OHdG levels were found to be significantly higher in the OCD group, compared to the control group (p=0.010, p=0.034, p=0.010, respectively); however, no significant difference was found in the SOD levels between two groups (p=0.10). There were no correlations between the CY-BOC scores, depression scores, duration of the disease and biochemical parameters (p>0.05, for all). Children with OCD were found to have higher antioxidant levels and oxidative DNA damage. The findings of this study support the role of oxidative stress in the pathogenesis of OCD. In this regard, any possible effect of adding antioxidants to conventional treatment can be investigated.