Pathophysiology Of Obsessive-compulsive Disorder Research Articles

Functional and Structural Neural Changes in Obsessive-compulsive Disorder after Pharmacotherapy.

Obsessive-compulsive disorder (OCD) is an important disorder which is disturbing the quality of life and is charac-terized by repetitive thoughts and behaviors, now in a different category in the Diagnostic and Statistical Manual for Mental Disorders Fifth Edition (DSM 5). Neuroimaging investigations are very useful to reveal a neurobiological model of the OCD. Studies conducted in the last quarter century have shown clear results and revealed that specific cortico-subcortical circuits could be involved in the occurrence of OCD symptomatology. These neuroimaging studies pointed out some im-portant findings for OCD patients. Our present information implicates some problems in some cortico-subcortical in the pathophysiology of OCD. In the present paper, final information on the neuroanatomy and neurochemistry of OCD was re-viewed, revising the effects of anti-obsessional drugs on the structural and functional neuroimaging studies. As can be seen in the review, drug treatments can generally affect the brain structurally and functionally, suggesting that brain of OCD tends to neuroplasticity. However, it is not clear that these effects of pharmacotherapy are related to anti-obsessional drugs per se or impact on the improvement of the disorder.

Altered Functional Connectivity Between the Cerebellum and the Cortico-Striato-Thalamo-Cortical Circuit in Obsessive-Compulsive Disorder.

Background: Altered resting-state functional connectivity of the cerebellum in obsessive-compulsive disorder (OCD) has been previously reported. However, the previous study investigating cerebellar–cerebral functional connectivity relied on a priori–defined seeds from specific networks. In this study, we aimed to explore the connectivity alterations of the cerebellum in OCD under resting-state conditions with a hypothesis-free approach. Methods: Thirty patients with OCD and 26 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Regional cerebral function was evaluated by measuring the fraction of amplitude of low-frequency fluctuation (fALFF). Regions with mean fALFF (mfALFF) alterations were used as seeds in seed correlation analysis (SCA). An independent samples t test was used to compare the differences in mfALFF and functional connection (FC) between the two groups. Pearson correlation analysis was performed to identify the association between functional neural correlates and OCD symptom severity evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Compared with the HC group, the OCD group showed significantly increased mfALFF values in bilateral cerebellar. The results of FC analysis showed weakened connectivity among the left Crus II, lobule VIII, and right striatum and between the right lobule VIII and the right striatum, and cingulate in the OCD group compared with the HC group. Some of the abovementioned results were associated with symptom severity. Conclusions: OCD patients showed abnormal spontaneous cerebellar activity and weakened functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical (CSTC) circuit (striatum and cingulate), suggesting that the cerebellum may play an essential role in the pathophysiology of OCD.

An MRI Study of the Metabolic and Structural Abnormalities in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric illness characterized by obsessions and/or compulsions. Its pathophysiology is still not well understood but it is known that the cortico-striatal-thalamic-cortical (CSTC) circuitry plays an important role. Here, we used a multi-method MRI approach combining proton magnetic resonance spectroscopy (H1-MRS) and diffusion tensor imaging (DTI) techniques to investigate both the metabolic and the microstructural white matter (WM) changes of the anterior cingulate cortex (ACC) in OCD patients as compared to healthy controls. Twenty-three OCD patients and 21 age-, sex-, and education-matched healthy volunteers participated in the study. Our 1H-MRS findings show increased levels of Glx in ACC in OCD. Further, significantly lower fractional anisotropy (FA) values were observed in OCD patients’ left cingulate bundle (CB) as compared to healthy controls. Finally, there was a negative correlation between FA in the left CB and level of obsessions, as well as the duration of the illness. Our findings reinforce the involvement of CSTC bundles in pathophysiology of OCD, pointing to a specific role of glutamate (glutamine) and WM integrity.

Localized Connectivity in Obsessive-Compulsive Disorder: An Investigation Combining Univariate and Multivariate Pattern Analyses.

Recent developments in psychoradiological researches have highlighted the disrupted organization of large-scale functional brain networks in obsessive-compulsive disorder (OCD). However, whether abnormal activation of localized brain areas would affect network dysfunction remains to be fully characterized. We applied both univariate analysis and multivariate pattern analysis (MVPA) approaches to investigate the abnormalities of regional homogeneity (ReHo), an index to measure the localized connectivity, in 88 medication-free patients with OCD and 88 healthy control subjects (HCS). Resting-state functional magnetic resonance imaging (RS-fMRI) data of all the participants were acquired in a 3.0-T scanner. First, we adopted a traditional univariate analysis to explore ReHo alterations between the patient group and the control group. Subsequently, we utilized a support vector machine (SVM) to examine whether ReHo could be further used to differentiate patients with OCD from HCS at the individual level. Relative to HCS, OCD patients showed lower ReHo in the bilateral cerebellum and higher ReHo in the bilateral superior frontal gyri (SFG), right inferior parietal gyrus (IPG), and precuneus [P < 0.05, family-wise error (FWE) correction]. ReHo value in the left SFG positively correlated with Yale–Brown Obsessive Compulsive Scale (Y-BOCS) total score (r = 0 0.241, P = 0.024) and obsessive subscale (r = 0.224, P = 0.036). The SVM classification regarding ReHo yielded an accuracy of 78.98% (sensitivity = 78.41%, specificity = 79.55%) with P < 0.001 after permutation testing. The most discriminative regions contributing to the SVM classification were mainly located in the frontal, temporal, and parietal regions as well as in the cerebellum while the right orbital frontal cortex was identified with the highest discriminative power. Our findings not only suggested that the localized activation disequilibrium between the prefrontal cortex (PFC) and the cerebellum appeared to be associated with the pathophysiology of OCD but also indicated the translational role of the localized connectivity as a potential discriminative pattern to detect OCD at the individual level.

Validating a dimension of doubt in decision-making: A proposed endophenotype for obsessive-compulsive disorder.

Doubt is subjective uncertainty about one’s perceptions and recall. It can impair decision-making and is a prominent feature of obsessive-compulsive disorder (OCD). We propose that evaluation of doubt during decision-making provides a useful endophenotype with which to study the underlying pathophysiology of OCD and potentially other psychopathologies. For the current study, we developed a new instrument, the Doubt Questionnaire, to clinically assess doubt. The random dot motion task was used to measure reaction time and subjective certainty, at varying levels of perceptual difficulty, in individuals who scored high and low on doubt, and in individuals with and without OCD. We found that doubt scores were significantly higher in OCD cases than controls. Drift diffusion modeling revealed that high doubt scores predicted slower evidence accumulation than did low doubt scores; and OCD diagnosis lower than controls. At higher levels of dot coherence, OCD participants exhibited significantly slower drift rates than did controls (q<0.05 for 30%, and 45% coherence; q<0.01 for 70% coherence). In addition, at higher levels of coherence, high doubt subjects exhibited even slower drift rates and reaction times than low doubt subjects (q<0.01 for 70% coherence). Moreover, under high coherence conditions, individuals with high doubt scores reported lower certainty in their decisions than did those with low doubt scores. We conclude that the Doubt Questionnaire is a useful instrument for measuring doubt. Compared to those with low doubt, those with high doubt accumulate evidence more slowly and report lower certainty when making decisions under conditions of low uncertainty. High doubt may affect the decision-making process in individuals with OCD. The dimensional doubt measure is a useful endophenotype for OCD research and could enable computationally rigorous and neurally valid understanding of decision-making and its pathological expression in OCD and other disorders.

Abnormal functional network of the thalamic subregions in adult patients with obsessive-compulsive disorder

The thalamus plays an important role in pathological mechanisms underlying obsessive-compulsive disorder (OCD). As the thalamus is a heterogeneous brain region, functional connectivity (FC) between thalamic subregions and other brain regions is worth investigating in OCD. In addition, the relationship between abnormal FC and clinical symptoms is still unclear. In this study, we used resting-state functional magnetic resonance imaging to scan 45 OCD patients and 43 well-matched healthy controls (HCs). Thalamic subregions were defined according to the Human Brainnetome Atlas. The fractional amplitude of low-frequency fluctuations (fALFF) and FC seeding-based connectivity were compared using a two-sample t-test. Correlations between abnormal FC and clinical symptoms were analyzed in OCD patients. Compared with HCs, increased fALFF was found in the bilateral thalamus, and increased FC was observed between the right posterior parietal thalamus (PPtha) and left middle occipital gyrus (LMOG) and between the right occipital thalamus (Otha) and right middle occipital gyrus (RMOG) in OCD patients. In addition, OCD patients had reduced FC between the left sensory thalamus (Stha) and left orbital inferior frontal gyrus, right PPtha and left prefrontal cortex, and between the right Otha and left inferior parietal gyrus (LIPG), respectively. Within the OCD group, the FC between right PPtha-LMOG was correlated with severity of clinical symptoms. These results revealed that the FC between the thalamus and occipital lobe is related to obsessive-compulsive symptoms in OCD patients. This finding provides more accurate information about the involvement of the thalamus in the pathophysiology of OCD.

Altered Cortico-Striatal Functional Connectivity During Resting State in Obsessive-Compulsive Disorder.

Background: Neuroimaging studies show that obsessive–compulsive disorder (OCD) is characterized by an alteration of the cortico–striato–thalamo–cortical (CSTC) system in terms of an imbalance of activity between the direct and the indirect loop of the CSTC. As resting-state functional connectivity (FC) studies investigated only specific parts of the CSTC in patients with OCD up to now, the present study aimed at exploring FC in the CSTC as a whole. Methods: We investigated potential alterations in resting-state FC within the CSTC system in 44 OCD patients and 40 healthy controls by taking into consideration all relevant nodes of the direct and indirect CSTC loop. Results: Compared to healthy controls, OCD patients showed an increased FC between the left subthalamic nucleus (STN) and the left external globus pallidus (GPe), as well as an increased FC between the left GPe and the left internal globus pallidus (GPi). Conclusion: These findings may contribute to a better understanding of the OCD pathophysiology by providing further information on the connectivity alterations within specific regions of the CSTC system. In particular, increased FC between the STN and the left GPe may play a major role in OCD pathology. This assumption is consistent with the fact that these regions are also the main target sites of therapeutic deep brain stimulation in OCD.

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

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. 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. 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. 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.

Altered network homogeneity of the default-mode network in drug-naive obsessive−compulsive disorder

BackgroundDefault-mode network (DMN) plays a key role in the pathophysiology of obsessive−compulsive disorder (OCD). However, the network homogeneity (NH) of DMN in OCD remains equivocal. ObjectiveThis study aimed to investigate abnormalities in the NH of the DMN at rest and the correlation between the NH of DMN and clinical variables in patients with OCD. MethodsThis study used the independent component analysis and unbiased hypothesis-driven NH method to analyze the resting-state functional magnetic resonance imaging data of 40 drug-naive patients with OCD and 40 age-, gender-, and education-matched healthy controls (HCs). ResultsPatients with OCD exhibited decreased NH values in the left ventral medial prefrontal cortex and bilateral posterior cingulate cortex (PCC)/precuneus (PCu) compared with HCs. Furthermore, analyses of receiver operating characteristic curves indicated that the decreased NH values in the right PCC/PCu may be used as a candidate neuroimaging marker to distinguish patients with OCD from HCs. ConclusionThese findings contribute new evidence of the participation of the altered NH of the DMN in the pathophysiology of OCD. Trial RegistrationStudy on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (ChiCTR-COC-17013301).

Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.

Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive-Compulsive Disorder.

We mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive-compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.

The Glutamate and the Immune Systems: New Targets for the Pharmacological Treatment of OCD.

In the last decades the pharmacological treatment of obsessivecompulsive disorder (OCD) has been significantly promoted by the effectiveness of selective serotonin (5-HT) reuptake inhibitors (SSRIs) and the subsequent development of the 5-HT hypothesis of OCD. However, since a large majority of patients (between 40% and 60 %) do not respond to SSRIs or strategies based on the modulation of the 5-HT system, it is now essential to search for other possible therapeutic targets. The aim of this paper was to review current literature through a PubMed and Google Scholar search of novel hypotheses and related compounds for the treatment of OCD, with a special focus on the glutammate and the immune systems. The literature indicates that glutamate, the main excitatory neurotransmitter, might play an important role in the pathophysiology of OCD. In addition, a series of clinical studies also supports the potential efficacy of drugs modulating the glutamate system. The role of the immune system alterations in OCD in both children and adults needs to be more deeply elucidated. In children, a subtype of OCD has been widely described resulting from infections driven by group A streptococcus β-hemolitic and belonging to the so-called "pediatric autoimmune neuropsychiatric disorders associated with streptococcus" (PANDAS). In adults, available findings are meager and controversial, although interesting. The glutamate and the immune systems represent two intriguing topics of research that hold promise for the development of open novel treatment strategies in OCD.

Deep Brain Stimulation for Obsessive Compulsive Disorder: Evolution of Surgical Stimulation Target Parallels Changing Model of Dysfunctional Brain Circuits.

Obsessive compulsive disorder (OCD) is a common, disabling psychiatric disease characterized by persistent, intrusive thoughts and ritualistic, repetitive behaviors. Deep brain stimulation (DBS) is thought to alleviate OCD symptoms by modulating underlying disturbances in normal cortico-striato-thalamo-cortical (CSTC) circuitry. Stimulation of the ventral portion of the anterior limb of the internal capsule (ALIC) and underlying ventral striatum (“ventral capsule/ventral striatum” or “VC/VS” target) received U.S. FDA approval in 2009 for patients with severe, treatment-refractory OCD. Over the decades, DBS surgical outcome studies have led to an evolution in the electrical stimulation target. In parallel, advancements in neuroimaging techniques have allowed investigators to better visualize and define CSTC circuits underlying the pathophysiology of OCD. A critical analysis of these new data suggests that the therapeutic mechanism of DBS for OCD likely involves neuromodulation of a widespread cortical/subcortical network, accessible by targeting fiber bundles in the ventral ALIC that connect broad network regions. Future studies will include advances in structural and functional imaging, analysis of physiological recordings, and utilization of next-generation DBS devices. These tools will enable patient-specific optimization of DBS therapy, which will hopefully further improve outcomes.

Memantine as an augmentation therapy in obsessive–Compulsive disorder

Obsessive Compulsive Disorders a mental illness, which is long lasting and the person has recurrent thoughts or mental images and compulsive acts, which the person is unable to resist. SSRI and TCA are primarily used drugs for obsessive-compulsive disorder (OCD), but in few patients these lead to less response and some other augmenting drugs have to be added along with them. A role for glutamatergic dysfunction in the pathophysiology of OCD has been found. We report 2 cases with a diagnosis of OCD where the patients did not show good response on YBOCS with SSRI and other adjunctive drugs like venlafaxine, resperidone in adequate dose and duration. When memantine was added (20 mg) the patient showed improvement on YBOCS where score reduced within the 6 weeks of augmentation.

Roles of 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in early- and late-onset obsessive-compulsive disorder.

Background:The C677T and A1298C mutations of 5,10-methylenetetrahydrofolate reductase (MTHFR) have been linked with conditions such as depression, bipolar disorder, and schizophrenia, but there are not clear the relationship between MTHFR polymorphisms and obsessive-compulsive disorder (OCD).Aim:The current study was planned to investigate the link between the MTHFR polymorphisms and OCD in patients to reveal any potential correlations that may be used as a novel marker in diagnosis of people who are in high-risk group of developing OCD.Materials and Methods:Blood samples from 64 highly characterized symptomatic cases and 64 gender- and age-matched control participants were analyzed for MTHFR C677T and A1298C gene variants. The MTHFR gene polymorphisms were detected through real-time polymerase chain reaction, followed by melting curve analysis. The results were tested with analysis of variance test and the differences with P < 0.05 were reported as statistically significant.Results:A statistically significant difference in age, education level, and marital status was found in the comparison of all groups in sociodemographic findings (P = 0.004, P = 0.001, and P = 0.001, respectively). A statistically significant difference was found in the comparison of the tic story of early- and late-onset OCD patients (P = 0.002). There was no significant difference in the genotype frequencies and allele distributions of MTHFR polymorphisms between the patients and controls (P > 0.05).Conclusion:The results suggest that MTHFR polymorphisms are unlikely to play a major role in the pathogenesis of OCD. Further studies are needed in biochemical data on folate metabolism to clarify the effect of the MTHFR polymorphisms in OCD pathophysiology.

Investigating the predictive value of different resting-state functional MRI parameters in obsessive-compulsive disorder

Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies of obsessive-compulsive disorder (OCD) have facilitated our understanding of OCD pathophysiology based on its intrinsic activity. However, whether the group difference derived from univariate analysis could be useful for informing the diagnosis of individual OCD patients remains unclear. We aimed to apply multivariate pattern analysis of different rs-fMRI parameters to distinguish drug-naive patients with OCD from healthy control subjects (HCS). Fifty-four drug-naive OCD patients and 54 well-matched HCS were recruited. Four different rs-fMRI parameter maps, including the amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo) and functional connectivity strength (FCS), were calculated. Training of a support vector machine (SVM) classifier using rs-fMRI maps produced voxelwise discrimination maps. Overall, the classification accuracies were acceptable for the four rs-fMRI parameters. Excellent performance was achieved when ALFF maps were employed (accuracy, 95.37%, p < 0.01), good performance was achieved by using ReHo maps, weaker performance was achieved by using fALFF maps, and fair performance was achieved by using FCS maps. The brain regions showing the greatest discriminative power included the prefrontal cortex, anterior cingulate cortex, precentral gyrus, and occipital lobes. The application of SVM to rs-fMRI features may provide potential power for OCD classification.

Obsessive Compulsive Disorder and Its Care - A Review

Actually 14 to 16th century in Europe some people have experienced that sexual or other thoughts were by devil then the journey start. 1910, Sigmund Freud said that obsessions and compulsive behaviours are symptoms of OCD. Obsessive compulsory disorder (OCD) is an anxiety disorder. Obsessive compulsive disorder causes the brain stuck on a particular thought or urge. Actually these patients are having a obsessive thoughts means they always occurring of images, several thoughts or pictures over and over in the mind. These thoughts or rituals can triggered more anxiety. These OCD patients can find out by the facts like washing, cleaning, checking and repeating. The American psychiatric association said that the females are more affected then the men. The OCD is a common , chronic (long lasting disorder) the people with OCD can feel the temporary relief from the anxiety if the person can untreated then they cause the more stress and the effects seen on the work, school and lead to serious effects on personal relationships. Actually obsessive compulsive disorder is a brain injury , it involves basal ganglion (Eg: encephalitis or trauma) usually there is no neurologic precipitant. The evidence suggesting a selective and potent serotonin(5-HT) reuptake blocker drugs are successful treatment in biological basis of OCD. The drugs with the other mechanism of action have not been effective more. The neurotransmitter plays an important role in pathophysiology of obsessive compulsive disorder.

Reduced prefrontal-temporal cortical activation during verbal fluency task in obsessive-compulsive disorder: A multi-channel near-infrared spectroscopy study

Functional neuroimaging studies by near-infrared spectroscopy (NIRS) have focused on the role of the prefrontal cortex (PFC) in the pathophysiology of obsessive-compulsive disorder (OCD). However, the reported areas in the PFC were inconsistent in OCD, and correlations between hemodynamic response and clinical symptoms have not been investigated. This study aimed to evaluate the hemodynamic response related to the verbal fluency task (VFT) and assess the relationship between activation and clinical status in OCD patients using a 52-channel NIRS with a wide coverage over the prefrontal and temporal cortices. Seventy patients with OCD and 70 age-, gender- and education level-matched healthy control subjects were examined by NIRS. The relative concentration changes of oxygenated hemoglobin ([oxy-Hb]) were measured. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to evaluate the severity of OCD symptoms. Compared to healthy controls group, OCD patients showed smaller [oxy-Hb] changes in most areas of the prefrontal and temporal cortex, including the bilateral orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), bilateral inferior prefrontal cortex (IPFC), bilateral frontopolar cortex (FPC), left superior temporal gyrus (STG), and bilateral middle temporal gyrus (MTG). Furthermore, the [oxy-Hb] changes in the right FPC were negatively correlated with the Y-BOCS obsessions score and Y-BOCS total score, and the [oxy-Hb] changes in the left OFC were negatively correlated with the Y-BOCS compulsions score. These results suggest that patients with OCD have reduced prefrontal-temporal cortex hemodynamic responses, and that the abnormalities of brain activation were associated with the severity of OCD symptoms.

Immune Aberrations in Obsessive-Compulsive Disorder: a Systematic Review and Meta-analysis.

Some lines of evidence have indicated that immune dysregulation could play a role in the pathophysiology of obsessive-compulsive disorder (OCD). However, results have been inconsistent across studies. Thus, a systematic review and meta-analysis of studies measuring immune mediators in participants with OCD compared to healthy controls (HC) was conducted. The PubMed/MEDLINE, PsycINFO, and EMBASE electronic databases were systematically searched from inception through June 21, 2018. Sixteen studies met inclusion criteria comprising data from 1001 participants (538 with OCD and 463 were HCs). Levels of TNF-α, IL-6, IL-1β, IL-4, IL-10, and interferon-γ did not significantly differ between participants with OCD and healthy controls. In addition, the ex vivo production of TNF-α and IL-6 by isolated macrophages did not significantly differ between participants with OCD and HCs. Nevertheless, included studies have varied in methodological quality with the enrollment of samples that differed regarding medication status, the proper matching of OCD participants and HCs, age groups, and the presence of psychiatric comorbidities. In conclusion, an association between immune dysregulation and OCD remains unproven. Future studies should consider enrolling larger and more homogeneous samples with OCD.

Genetic Associations of Serotoninergic and GABAergic Genes in an Extended Collection of Early-Onset Obsessive-Compulsive Disorder Trios.

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder whose etiology includes important genetic contributions. In a previous transmission disequilibrium study in which 75 complete trios were included, single-nucleotide polymorphisms (SNPs) in serotoninergic and GABAergic genes were associated with early-onset OCD. Our aim was to assess those findings in an extended collection of early-onset OCD trios. A transmission disequilibrium test for SNPs in HTR1B (rs2000292), SLC18A1 (rs6586896), GAD1 (rs3791860), and GAD2 (rs8190748) was performed in a total of 101 early-onset OCD trios, from which 26 trios were newly recruited for the purpose of the present analysis. All the SNPs were overtransmitted from parents to OCD probands (p < 0.012, significant after Bonferroni correction). These results are consistent with the previous findings and constitute more evidence of the role of genetic factors related to serotoninergic and GABAergic pathways in the pathophysiology of early-onset OCD.