Etiology Of Obsessive-compulsive Disorder Research Articles

The role of immunity and inflammation in obsessive-compulsive disorder and related conditions

Introduction In recent years, there has been a growing interest in the potential consequences of disruptions in the inflammatory and immune systems on the onset of obsessive-compulsive disorder (OCD) and associated conditions, such as Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) and Tourette syndrome (TS). While this area of inquiry is undeniably captivating, the available data remain somewhat controversial and limited in scope.ObjectivesThe aim of this paper is to conduct an exhaustive examination and evaluation of the existing body of literature concerning aberrations in inflammatory and immune system processes within the context of OCD, PANDAS, and TS.MethodsThis narrative review entailed a comprehensive search of English language papers on PubMed and Google Scholar from January 1985 to July 31, 2023.Results The data collected up to this point suggest that the underlying mechanisms at play may differ depending on the age of the patients and the specific disorder being investigated. Notably, PANDAS seems to have a stronger connection with infections that trigger autoimmunity, which may not necessarily be limited to those resulting from Group A beta-haemolytic streptococcal (GABHS) infections, as previously assumed. In the case of TS, autoimmunity appears to play a significant role, especially when combined with individual susceptibilities stemming from both genetic and environmental factors. As for adult OCD, while the available data are somewhat scattered and occasionally based on relatively small groups of patients, they do indicate that the immune system and inflammatory processes are involved in the disorder’s pathophysiology. However, it remains uncertain whether these processes are primary driving forces or secondary reactions.ConclusionsIn summary, when viewed collectively, the current research findings unveil promising avenues for exploring the underlying causes of OCD and related disorders. They also hold the potential for the development of innovative therapeutic approaches that go beyond the current pharmacological paradigms.Disclosure of InterestNone Declared

Establishing an OCD Model in BALB/c Mice Using RU24969: A Molecular and Behavioural Study of Optimal Dose Selection.

Obsessive-compulsive disorder (OCD) is a disabling disease characterized by distressing obsessions and repetitive compulsions. The etiology of OCD is poorly known, and mouse modeling allows to clarify the genetic and neurochemical basis of this disorder and to investigate potential treatments. This study evaluates the impact of the 5-HT1B agonist RU24969 on the induction of OCD-like behaviours in female BALB/c mice (n = 30), distributed across five groups receiving varying doses of RU24969. Behavioural assessments, including marble test, tail suspension test, sucrose preference test, forced swim test, and nestlet shredding test, were conducted. Gene expression and protein quantitation of Gabra1 and serotonin transporter in mouse brain were also performed. Marble-burying behaviour increased significantly at high doses of RU24969 (15-20 mg/kg). The forced swimming test consistently showed elevated values at the same high concentrations, compared to the control. Altered reward-seeking behaviour was indicated by the sucrose preference test, notably at 15 and 20 mg/kg doses of RU24969. Nestlet shredding results did not show statistical significance among the tested animal groups. Gene expression analysis revealed reduced Gabra1 expression with increasing doses of RU, while serotonin transporter was not related to varying doses of RU24969. Western blotting corroborated these trends. The results underscore complex interactions between the serotonin system, GABAergic signaling, and OCD-relevant behaviours and suggest the use of intraperitoneal injection of 15 mg/kg of RU24969 to induce OCD-like behaviour in BALB/c mouse models.

Temporal dynamics of autonomic nervous system responses under cognitive-emotional workload in obsessive-compulsive disorder.

Dysregulation of the autonomic nervous system (ANS) is commonly observed in various mental disorders, particularly when individuals engage in prolonged cognitive-emotional tasks that require ANS adjustment to workload. Although the understanding of the temporal dynamics of sympathetic and parasympathetic tones in obsessive-compulsive disorder (OCD) is limited, analyzing ANS reactions to cognitive-emotional workload could provide valuable insights into one of the underlying causes of OCD. This study investigated the temporal dynamics of heart rate (HR) and pupil area (PA) while participants with OCD and healthy volunteers solved antisaccade tasks, with affective pictures serving as central fixation stimuli. The data of 31 individuals with OCD and 30 healthy volunteers were included in the study, comprising three separate blocks, each lasting approximately 8 min. The results revealed an increase in sympathetic tone in the OCD group, with the most noticeable rise occurring during the middle part of each block, particularly during the presentation of negative stimuli. Healthy volunteers demonstrated adaptive temporal dynamics of HR and PA from the first block to the last block of tasks, whereas individuals with OCD exhibited fewer changes over time, suggesting a reduced adaptation of the ANS sympathetic tone to cognitive-emotional workload in OCD.

A closer look to neural pathways and psychopharmacology of obsessive compulsive disorder.

The intricate neural pathways involved in obsessive-compulsive disorder (OCD) affect areas of our brain that control executive functioning, organization, and planning. OCD is a chronic condition that can be debilitating, afflicting millions of people worldwide. The lifetime prevalence of OCD in the US is 2.3%. OCD is predominantly characterized by obsessions consisting of intrusive and unwanted thoughts, often with impulses that are strongly associated with anxiety. Compulsions with OCD encompass repetitive behaviors or mental acts to satisfy their afflicted obsessions or impulses. While these factors can be unique to each individual, it has been widely established that the etiology of OCD is complex as it relates to neuronal pathways, psychopharmacology, and brain chemistry involved and warrants further exploration.

Gender differences in the symptoms and physiological basis of Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is an anxiety disorder related to repetitive behaviors and intrusive thoughts. Individuals with OCD experience conscious, self-imposed compulsions and counter-compulsions, which result in high levels of anxiety and difficulties in social interactions. OCD is a common mental disorder with onset often in adolescence. Gender differences in OCD exist, with males reporting earlier symptom onset, and females experiencing symptoms during adolescence, pregnancy, or postpartum, particularly related to contamination and/or aggressive obsessions. Neurobiological factors play a role in OCD etiology. Genetic studies show hereditary tendencies, with gender differences observed. Brain structure research identifies differences between male and female patients. Dopamine and plasma norepinephrine are implicated in OCD pathogenesis. Understanding gender differences is crucial for OCD diagnosis and treatment. Further research is needed to validate and explain these differences in order to inform advancements in OCD treatment approaches. This paper summarizes and discusses the relationship between OCD and gender, focusing on epidemiological characteristics, symptoms, and physiological basis of OCD, emphasizing gender differences. Future research directions in the field of OCD are presented.

Microbial Reprogramming in Obsessive-Compulsive Disorders: A Review of Gut-Brain Communication and Emerging Evidence.

Obsessive-compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches.

Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction.

This review provides an overview of obsessive-compulsive disorder (OCD) symptoms, including the four partially distinct subtypes of the disorder, current diagnostic criteria, and common comorbidities. Critically, it focuses on the etiology of OCD, including its underlying neuropathology, and examines cognitive dysfunction in OCD. This review study was conducted by library method. We show how dysfunction in cortico-striato-thalamo-cortical (CSTC) circuits may underpin symptoms; and shed light on the putative neurochemistry within these loops such as the role of serotonin, dopamine, and glutamate systems. We also show how OCD is characterized by cognitive dysfunction including problems in cognitive flexibility, visuospatial memory, response inhibition, and goal-directed behavior, linked to aberrant activity within CSTC circuits. In brief, research questions we shed light on include (1) what are the symptoms in OCD; (2) what is the etiology of the disorder and do existing models explain OCD; and (3) what are key cognitive deficits in OCD and do these improve with treatment?

Early Identification and Intervention in Pediatric Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by persistent thoughts with subsequent repetitive behaviors. Interventions that are effective for adult OCD cannot simply be generalized to pediatric OCD, since OCD in children and adolescents usually has a different clinical presentation, etiology and course from adult OCD. Delayed and inadequate treatment is associated with a worse prognosis, making the need for early identification and intervention in pediatric OCD very urgent. In this paper, we reflected on the current constraints that make early interventions for pediatric OCD unpromoted and reviewed the approaches with potential application for early identification and early intervention in pediatric OCD, categorized by three-level prevention stages corresponding to a clinical staging model. Since the etiology of pediatric OCD is still unclear, primary prevention is most lacking, and early interventions for pediatric OCD are currently focused on the secondary prevention stage, which aims to prevent the conversion of obsessive-compulsive symptoms into full-blown OCD; tertiary prevention mostly focuses on the alleviation of mild to moderate OCD, while interventions for co-morbidities are still in their infancy. We closed by considering the important research questions on this topic.

Investigation of the Relationship of Serotonin, Dopamine and Their Metabolites with α -Synuclein in Obsessive Compulsive Disorder

Objectives: Obsessive compulsive disorder (OCD) is a mental disorder characterized by obsessions and/or compulsions. Impulsive features play a role in the etiology, symptomatology and clinical presentation of OCD. α-synuclein which plays a role in dopaminergic and serotonergic neurotransmission has been shown to be effective in impulse control. The aim of this study is to examine the levels of α-synuclein, serotonin (5-hydroxytryptamine; 5-HT), dopamine, dopamine β-hydroxylase (DBH), 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA) and heat shock protein 70 (HSP70) in OCD. Methods: Twenty-six OCD patients and age-gender matched 23 healthy volunteers were included in this study. Biochemical parameters were analyzed by enzyme-linked immunosorbent assay method. Patients were evaluated with Barratt Impulsivity Scale (BIS) and Dimensional Obsession Compulsion Scale (DOCS). Results: Compared with the controls, significant reduction of 5-HT, dopamine and DBH levels while significant increase of α-synuclein, HVA and HSP70 levels was found in patients with OCD. Moreover, α-synuclein levels were significantly negatively correlated with 5-HT, dopamine and DBH, while significantly positively correlated with HVA, 5-HIAA and HSP70. HTR and dopamine levels were found to be associated with the subscale of BIS. Dopamine and DBH levels were found to be associated with the subscale of DOCS. Conclusions: It may be suggested that α-synuclein is associated with dopaminergic and serotinergic pathways, and may provide important contributions for elucidating the etiology of OCD. It can be suggested that the effect of dopamine is more than 5-HT, based on the fact that not only dopamine but also DBH is correlated with OCD symptoms.

Identifying organic causes of obsessive-compulsive disorder (OCD): The Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD)

Identifying organic causes of obsessive-compulsive disorder (OCD): The Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD)

A computational network dynamical modeling for abnormal oscillation and deep brain stimulation control of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is associated with multi-nodal abnormalities in brain networks, characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviours or mental acts (compulsions), which might manifest as pathological low-frequency oscillations in the frontal EEG and low-frequency bursting firing patterns in the subthalamus nucleus (STN). Abnormalities in the cortical-striatal-thalamic-cortical (CSTC) loop, including dysregulation of serotonin, dopamine, and glutamate systems, are considered to contribute to certain types of OCD. Here, we extend a biophysical computational model to investigate the effect of orbitofronto-subcortical loop abnormalities on network oscillations. Particularly, the OCD lesion process is simulated by the loss of connectivity from striatal parvalbumin interneurons (PV) to medium spiny neurons (MSNs), excessive activation to the hyperdirect pathway, and high dopamine concentrations. By calculatinglow-frequency oscillation power in the STN, STN burst index, and average firing rates levels of the cortex and thalamus, we demonstrate that the model can explain the pathology of glutamatergic and dopamine system dysregulation, the effects of pathway imbalance, and neuropsychiatric treatment in OCD. In addition, results indicate the abnormal brain rhythms caused by the dysregulation of orbitofronto-subcortical loop may serve as a biomarker of OCD. Our studies can help to understand the cause of OCD, thereby facilitating the diagnosis of OCD and the development of new therapeutics.

Prenatal and Early Childhood Infections and Subsequent Risk of Obsessive-Compulsive Disorder and Tic Disorders: A Nationwide, Sibling-Controlled Study

BackgroundPostinfectious autoimmune processes are hypothesized to be causally related to both obsessive-compulsive disorder (OCD) and tic disorders, but current evidence is conflicting. This study examined whether prenatal maternal (and paternal, as an internal control) infections and early childhood infections in the offspring (i.e., during the first 3 years of life) were associated with a subsequent risk of OCD and Tourette syndrome or chronic tic disorder (TS/CTD). MethodsIndividuals exposed to any prenatal maternal infection (n = 16,743) and early childhood infection (n = 264,346) were identified from a population-based birth cohort consisting of 2,949,080 singletons born in Sweden between 1973 and 2003 and were followed through 2013. Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Sibling analyses were performed to control for familial confounding. ResultsAt the population level, and after adjusting for parental psychiatric history and autoimmune diseases, a significantly increased risk of OCD and TS/CTD was found in individuals exposed to prenatal maternal (but not paternal) infections (OCD: HR, 1.33; 95% CI, 1.12–1.57; TS/CTD: HR, 1.60; 95% CI, 1.23–2.09) and early childhood infections (OCD: HR, 1.19; 95% CI, 1.14–1.25; TS/CTD: HR, 1.34; 95% CI, 1.24–1.44). However, these associations were no longer significant in the sibling analyses. ConclusionsThe results do not support the hypothesis that prenatal maternal or early-life infections play a direct causal role in the etiology of either OCD or TS/CTD. Instead, familial factors (e.g., genetic pleiotropy) may explain both the propensity to infections and the liability to OCD and TS/CTD.

Altered Regional Activity and Network Homogeneity within the Fronto-Limbic Network at Rest in Medicine-Free Obsessive-Compulsive Disorder.

Functional abnormalities in brain areas within the fronto-limbic network have been widely reported in obsessive–compulsive disorder (OCD). However, region- and network-level brain activities of the fronto-limbic network at rest have not been simultaneously investigated in OCD. In this study, 40 medicine-free and non-comorbidity patients with OCD and 38 age-, education-, and gender-matched healthy controls (HCs) underwent a resting-state functional magnetic-resonance-imaging scan. Fractional amplitude of low-frequency fluctuations (fALFF), network homogeneity (NH), and support vector machine were used to analyze the data. Patients with OCD showed increased fALFF in the right orbital frontal cortex (OFC), increased NH in the left OFC, and decreased NH in the right putamen. Decreased NH of the right putamen was negatively correlated with the Y-BOCS total and compulsive behavior scores. Furthermore, a combination of NH in the left OFC and right putamen could be applied to differentiate OCD from HCs with optimum specificity and sensitivity. The current findings emphasize the crucial role of the fronto-limbic network in the etiology of OCD.

STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive-Compulsive Disorder.

Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in the pathogenesis of OCD in MS. Methods: To obtain gene–gene interactions for MS and OCD, the STRING database was used. Cytoscape was then used to reconstruct and visualize graphs. Then, ToppGene and Enrichr were used to identify the main pathological processes and pathways involved in MS-OCD novel genes. Additionally, to predict transcription factors and microRNAs (miRNAs), the Enrichr database and miRDB database were used, respectively. Results: Our bioinformatics analysis showed that the signal transducer and the activator of transcription 3 (STAT3) and neurotrophic receptor tyrosine kinase 2 (NTRK2) genes had connections with 32 shared genes between MS and OCD. Furthermore, STAT3 and NTRK2 had the greatest enrichment parameters (i.e., molecular function, cellular components, and signaling pathways) among ten hub genes. Conclusions: To summarize, data from our bioinformatics analysis showed that there was a significant overlap in the genetic components of MS and OCD. The findings from this study make two contributions to future studies. First, predicted mechanisms related to STAT3 and NTRK2 in the context of MS and OCD can be investigated for pharmacological interventions. Second, predicted miRNAs related to STAT3 and NTRK2 can be tested as biomarkers in MS with OCD comorbidity. However, our study involved bioinformatics research; therefore, considerable experimental work (e.g., postmortem studies, case–control studies, and cohort studies) will need to be conducted to determine the etiology of OCD in MS from a mechanistic view.

Perceived traumatic and stressful etiology of obsessive-compulsive disorder

A growing body of research has highlighted connections between obsessive-compulsive disorder (OCD) symptoms and traumatic and stressful life events. However, findings regarding the impact of traumatic and stressful events on posttraumatic stress symptoms are mixed, with some studies suggesting that the perception of an event as traumatic—regardless of the strict definition of trauma—may be most predictive of outcomes. Despite this, research has yet to ask individuals with OCD, themselves, why they believe their OCD developed; instead, findings linking trauma exposure and OCD are largely causally extrapolated. The current study examined the perceptions of OCD etiology in 45 individuals with OCD enrolled in residential treatment and qualitative responses were coded as traumatic, stressful, or other (i.e., non-event) etiologies. Nearly half of the sample (44.4%) believed their OCD developed following an identifiable event, six of whom identified a distinguishable traumatic event (13.3% overall). Individuals with perceived traumatic etiologies consistently endorsed engagement in more types of obsessions and compulsions, particularly in the past, and implicated themes of symmetry/exactness, repeating, checking, scrupulosity, pathological doubt, and hoarding. Findings suggest that events that occur pre-OCD onset may be likely to be perceived as the catalyst for OCD and may ultimately impact the theme and severity of symptoms in intuitive ways. • This study examined individual's subjective perceptions of why their OCD developed. • Nearly half of the sample attribute their OCD etiology to an identifiable event. • Traumatic etiology is more strongly related to symptoms than stressful etiology. • Traumatic etiology is related to obsessions and compulsions, especially in the past. • Traumatic etiology is consistently related to symmetry obsessions and compulsions.

The Possible Role of Vitamin D and Autoimmunity in the Etiology of Obsessive-Compulsive Disorder.

The Possible Role of Vitamin D and Autoimmunity in the Etiology of Obsessive-Compulsive Disorder.

Left Amygdala Functional Connectivity Decreased after Fear of Negative Events was Disregarded in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a chronic and debilitating mental disorder that affects patients throughout their lives, leading to a diminished quality of life for patients and families, reduced productivity, and higher health care costs. It is of clinical and theoretical importance to investigate a more efficacious therapeutic approach for OCD and the neurophysiological mechanism underlying the efficacy of treatment, potentially associated with the etiology of OCD. Recently, a novel psychotherapy designated cognitive-coping therapy (CCT) has been reported to have a large effect size in OCD treatment. CCT hypothesizes that fear of negative events plays a crucial role in OCD. The study entitled “Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder” attempted to investigate the potential neurophysiological mechanism underlying the efficacy of CCT for OCD. The study provides crystal evidence showing that 4-week pharmacotherapy plus CCT decreases the left amygdala seed-based functional connectivity (LA-FC) with the right anterior cingulate gyrus and the left paracentral lobule/the left superior parietal/left inferior parietal, and 4-week CCT decreases the LA-FC with the left middle occipital gyrus/the left superior parietal. The alteration of the LA-FC with the right anterior cingulate gyrus positively correlates to the reduction of the Yale-Brown obsessive-compulsive scale (Y-BOCS) score. Therefore, it provides new insights into understanding the neurophysiology and neuropsychology behind the onset and treatment of OCD.

The use of esketamine in comorbid treatment resistant depression and obsessive compulsive disorder following extensive pharmacogenomic testing: a case report

BackgroundMajor depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive–compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal–thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms.Case presentationWe present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient’s treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine.ConclusionThis case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD.

Cognitive Beliefs Across the Symptom Dimensions of Pediatric Obsessive-Compulsive Disorder: Type of Symptom Matters

The cognitive model of obsessive-compulsive disorder (OCD) posits that dysfunctional cognitive beliefs are crucial to the onset and maintenance of OCD; however, the relationship between these cognitive beliefs and the heterogeneity of OCD symptoms in children and adolescents remains unknown. We examined how the major belief domains of the cognitive model (inflated responsibility/threat estimation, perfectionism/intolerance of uncertainty, importance/control of thoughts) and dysfunctional metacognitions were related to OCD symptoms across the following dimensions: doubting/checking, obsessing, hoarding, washing, ordering, and neutralization. Self-report ratings from 137 treatment-seeking youth with OCD were analyzed. When cognitive beliefs and symptom dimensions were analyzed in tandem, inflated responsibility/threat estimation and dysfunctional metacognitions were uniquely related to doubting/checking, obsessing, and hoarding and perfectionism/intolerance of uncertainty to ordering. Cognitive beliefs explained a large proportion of variation in doubting/checking (61%) and obsessing (46%), but much less so in ordering (15%), hoarding (14%), neutralization (8%), and washing (3%). Similar relations between cognitive beliefs and symptom dimensions were present in children and adolescents. Cognitive beliefs appear to be relevant for pediatric OCD related to harm, responsibility, and checking, but they do not map clearly onto contamination and symmetry-related symptoms. Implications for OCD etiology and treatment are discussed.

GENETICS OF OBSESSIVE-COMPULSIVE DISORDER

Obsessive-compulsive disorder (OCD) is characterized by recurrent episodes of obsessive thoughts, fears, and actions, which, in the opinion of the patient, can defuse frightening events. A patient himself is aware of his condition, but cannot prevent it by a simple effort of will. The prevalence of OCD in the general population varies between 0.7% and 3.0%. Patients with OCD often can have a lifetime diagnosis of other psychopathology – an anxiety disorder, depressive disorder, tic disorder and others. In addition, the OCD symptoms often accompany other mental disorders, such as schizophrenia, bipolar disorder, eating disorder and others.
 Family studies in OCD showed that the disorder risk of first-degree relatives of individuals with OCD were approximately 15%, that more likely to develop OCD than its prevalence in the general population. This indicates the presence of a genetic component in the OCD development, that is also confirmed by the significant reliable value of the heritability of OCD (42-53%). Males have an earlier age at onset of OCD than females. Moreover, males more likely to have symptoms in the forbidden thoughts and symmetry dimensions and females more likely to have symptoms in the cleaning dimension. In addition, geographical and cultural factors may shape the content of obsessions and compulsions.
 There are four publications that have shown OCD genetic linkage with defined regions of three chromosomes: 9p24, 3q27-28 and 14q23-32. It was also found that the region of chromosome 3q27-28 contains three genes of serotonin receptor subunits – HTR3C (5HT3C), HTR3D (5HT3D) and HTR3E (5HT3E). These genes can be candidate genes for OCD. In addition, the HTR3C gene (3q27.1) is expressed in the brain cells, where it produces the serotonin receptor 3 subunit, which is a very important neurotransmitter. All three genes involved in the pathogenesis of not only OCD, but also of schizophrenia.
 Now, according to scientific reviews and «MalaCard: The Human Disease Database» above 40 OCD candidate genes were offered by various researchers. But almost all these studies were conducted on statistically insignificant samples (mostly from several dozens to several hundred individuals), which gave discrepant findings. In addition, not fully used methodological possibilities, for example, case-control samples were used, but family studies were not used. For this reason, the Canadian researcher S. Taylor (2013) conducted a meta-analysis of the findings of 113 studies and obtained high reliable confirmation of an assumption that variants of several genes are involved in the risk of OCD. Two of these genes associated with metabolism of serotonin (SLC6A4 and HTR2A) and two genes, in males only, are involved in catecholamine modulation (COMT and MAOA). Some more three genes have moderate reliability, two of which are associated with the dopamine system (DRD3 and DAT1) and one is associated with the glutamate system (SLC1A1). In addition, in S. Taylor’s opinion, 13 candidate genes attract an attention and merit further investigation.
 The results of genetic studies showed that OCD has a polygenic nature, because it is associated with multiple genes, everyone of them makes small contributions to a risk for the disorder. To reveal of these small effects, further studies of fairly large samples are needed. In addition, environmental factors may be involved in the OCD etiology that further exploration of gene–gene and gene–environment interactions is needed. To identify reliable OCD candidate genes all comorbidities must take into account. The OCD picture is extremely various not only in a lifetime of one patient, but between patients within the same family that indicates genetic heterogeneity of the disorder, which complicates the study in addition. These problems induce to study the genetic nature and environmental risk factors of OCD to ensure an earliest and most accurate diagnosis of OCD with due regard for environmental factors.