Etiology Of Obsessive-compulsive Disorder Research Articles

Deep Brain Stimulation for Obsessive-Compulsive Disorder

CME Educational Objectives 1. Provide an overview of the history and origins of deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD). 2. Describe the various neuroanatomic targets of DBS implant for OCD as well as the neurocircuitry involved. 3. Explain the effects of DBS for OCD, both intended and unintended, as well as the promise the treatment holds for select treatment-resistant OCD patients. Obsessive-compulsive disorder (OCD) is a chronic anxiety disorder that affects approximately 2% to 3% of the population. 1 OCD is characterized by persistent, intrusive, and distressing thoughts (obsessions) and ritualistic behaviors (compulsions), such as counting, organizing, or cleaning, which are used to lessen anxiety caused by the obsessive thoughts. The symptoms of OCD generally manifest in childhood or adolescence and may result in significant impairment in everyday functioning. The etiology of OCD is hypothesized to involve a combination of genetic and environmental factors.

Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive–compulsive symptoms

Clinical observations indicate that atypical antipsychotics, especially clozapine, induce obsessive-compulsive (OC) symptoms in schizophrenia patients. Recent data from neuroimaging and clinical trials suggest a role for altered glutamate neurotransmission in the etiology of OC disorder (OCD), and SLC1A1, GRIN2B, and GRIK2 have all been reported to regulate glutamate transmission and affect OCD pathophysiology. This study aimed to determine whether SLC1A1, GRIN2B, and GRIK2 are associated with clozapine-induced OC symptoms. A total of 250 clinically stable schizophrenia patients receiving clozapine treatment were recruited. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to evaluate the severity of OC symptoms. Based on their Y-BOCS scores, 250 patients were divided into the OC and non-OC groups (patients with or without OC symptoms, respectively). Additionally, three reported OCD susceptibility polymorphisms, SLC1A1 (rs2228622), GRIN2B (rs890), and GRIK2 (rs1556995), were genotyped. Trends of association with OC symptoms were observed in rs2228622A and rs890T alleles. SLC1A1 and GRIN2B interaction was found in the significant two-locus gene-gene interaction model (p = 0.0021), using the multifactor dimensionality reduction method. Further analysis showed a significant interaction between SLC1A1 and GRIN2B on the Y-BOCS score (F 6, 137 = 7.650, p < 0.001), and individuals with AA/TT genotypes had a significantly higher mean Y-BOCS score than those with other genotypes, except AG/TT. These results suggest that SLC1A1, GRIN2B, and interactions between the two may potentially confer a susceptibility to OC symptoms in schizophrenia patients receiving clozapine.

Meta‐analysis of association between obsessive‐compulsive disorder and the 3′ region of neuronal glutamate transporter gene SLC1A1

The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3' end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P = 0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N = 358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P = 0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD.

A review of metacognition in psychological models of obsessive–compulsive disorder

Cognitive–behavioural models and interventions for obsessive–compulsive disorder (OCD) have always included some metacognitive elements but until recently these have been predominantly construed of as cognitive as opposed to metacognitive processes. Increasingly, psychological models of OCD are now recognising the importance of metacognitive constructs in the maintenance and treatment of the disorder. Metacognitive models emphasise the importance of thinking processes, and thus represent a step away from traditional cognitive approaches which focused on the content of thoughts. This article reviews the current literature on metacognition in psychological models of OCD with an emphasis on: the role of metacognition in theoretical models of OCD and evidence to support this role; measures of metacognition in OCD; and, metacognitive treatment approaches for OCD and the evidence to support these approaches. The evidence indicates that metacognition has a key role in the aetiology of OCD. Treatment outcome research has indicated promising results, with several trials indicating clinically and statistically significant improvements using metacognitive‐based approaches. However, there is a need for larger, controlled trials with longer follow‐up periods to improve upon the methodological limitations of studies conducted to date.

Genome-wide association study of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

Reduction of N-acetylaspartate in the medial prefrontal cortex correlated with symptom severity in obsessive-compulsive disorder: meta-analyses of (1)H-MRS studies.

Structural and functional neuroimaging findings suggest that disturbance of the cortico–striato–thalamo–cortical (CSTC) circuits may underlie obsessive-compulsive disorder (OCD). However, some studies with 1H-magnetic resonance spectroscopy (1H-MRS) reported altered level of N-acetylaspartate (NAA), they yielded inconsistency in direction and location of abnormality within CSTC circuits. We conducted a comprehensive literature search and a meta-analysis of 1H-MRS studies in OCD. Seventeen met the inclusion criteria for a meta-analysis. Data were separated by frontal cortex region: medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex, orbitofrontal cortex, basal ganglia and thalamus. The mean and s.d. of the NAA measure were calculated for each region. A random effects model integrating 16 separate datasets with 225 OCD patients and 233 healthy comparison subjects demonstrated that OCD patients exhibit decreased NAA levels in the frontal cortex (P=0.025), but no significant changes in the basal ganglia (P=0.770) or thalamus (P=0.466). Sensitivity analysis in an anatomically specified subgroup consisting of datasets examining the mPFC demonstrated marginally significant reduction of NAA (P=0.061). Meta-regression revealed that NAA reduction in the mPFC was positively correlated with symptom severity measured by Yale–Brown Obsessive Compulsive Scale (P=0.011). The specific reduction of NAA in the mPFC and significant relationship between neurochemical alteration in the mPFC and symptom severity indicate that the mPFC is one of the brain regions that directly related to abnormal behavior in the pathophysiology of OCD. The current meta-analysis indicates that cortices and sub-cortices contribute in different ways to the etiology of OCD.

The predictive value of interpersonal schemas, perfectionism, and thought action-fusion in obsessive-compulsive disorder / Obsesif-kompulsif bozuklukta kişilerarası şemalar, mükemmeliyetçilik ve düşünce-eylem kaynaşmasının yordayıcı rolü

The predictive value of interpersonal schemas, perfectionism, and thought action-fusion in obsessive-compulsive disorder Objective: Cognitive vulnerability factors are central in the etiology of obsessive-compulsive disorder. Nosological classifications among symptom clusters have been developed to enable the understanding of possible mechanisms underlying obsessive compulsive symptoms. Previous researchers have emphasized that perfectionist attitudes and thought action-fusion link to increase in obsessive compulsive symptom severity in clinical and nonclinical samples. However, multi-dimensional relations between obsessive compulsive symptoms and vulnerability factors such as interpersonal schemas have received little attention. This study examined connections between cognitive vulnerability factors and obsessive-compulsive symptoms. Method: The data collected from 263 university students. Associations between variables were analyzed by using structural equation modeling. Results: The results of the study indicated that dysfunctional interpersonal schemas were the most hazardous factors that predict perfectionist attitudes, thought action-fusion, and symptom severity in obsessive compulsive disorder. Washing and precision were the final manifestation symptoms mediated by checking. Maladaptive interpersonal schemas, perfectionist attitudes, and thought action-fusion were all vulnerability agents in the development of obsessive compulsive symptoms. Checking played a prominent role in exacerbation of obsessive –compulsive symptoms. Conclusion: Onset and maintenance of obsessive-compulsive disorder is a multidimensional process. Negativistic interpersonal beliefs seem to be an important risk factor. Findings are discussed in the light of current theoretical considerations.

Genome-Wide Linkage Analysis of Obsessive-Compulsive Disorder Implicates Chromosome 1p36

Obsessive-compulsive disorder (OCD) has a complex etiology involving both genetic and environmental factors. However, the genetic causes of OCD are largely unknown, despite the identification of several promising candidate genes and linkage regions. Our objective was to conduct genetic linkage studies of the type of OCD thought to have the strongest genetic etiology (i.e., childhood-onset OCD), in 33 Caucasian families with ≥2 childhood-onset OCD-affected individuals from the United States (n = 245 individuals with genotype data). Parametric and nonparametric genome-wide linkage analyses were conducted with Morgan and Merlin in these families using a selected panel of single nucleotide repeat polymorphisms from the Illumina 610-Quad Bead Chip. The initial analyses were followed by fine-mapping analyses in genomic regions with initial heterogeneity logarithm of odds (HLOD) scores of ≥2.0. We identified five areas of interest (HLOD score ≥2) on chromosomes 1p36, 2p14, 5q13, 6p25, and 10p13. The strongest result was on chromosome 1p36.33-p36.32 (HLOD = 3.77, suggestive evidence for linkage after fine mapping). At this location, several of the families showed haplotypes co-segregating with OCD. The results of this study represent the strongest linkage finding for OCD in a primary analysis to date and suggest that chromosome 1p36, and possibly several other genomic regions, may harbor susceptibility loci for OCD. Multiple brain-expressed genes lie under the primary linkage peak (approximately 4 megabases in size). Follow-up studies, including replication in additional samples and targeted sequencing of the areas of interest, are needed to confirm these findings and to identify specific OCD risk variants.

Disgust mediates the relation between attentional shifting and contamination aversion

Background and objectivesAversion of contaminants is important for several psychiatric disorders, particularly contamination-based obsessive-compulsive disorder (OCD). Recent theoretical models have proposed that the ability to control one's attention, especially when processing affectively laden information, is important in the etiology of pathological anxiety. The present study tested the relations between attentional control, affective arousal, and behavioral approach toward contaminants (contamination aversion). MethodsThirty-three non-selected (undergraduate university students) participants completed a measure of trait attentional control and three behavioral approach tasks, which measured emotional reactivity and approach toward contaminants. ResultsPreliminary analyses showed that poorer attentional control and greater affective arousal predicted less behavioral approach toward contaminants. Modeling of direct and indirect relations showed that poor attentional shifting ability and greater subjective disgust were related to less behavioral approach. Moreover, disgust fully mediated the relation between attentional shifting and behavioral approach. LimitationsThe present study used a convenience sample, which is not representative of the general population or individuals with OCD; therefore, research using clinical samples is necessary before making clinical interpretations. Moreover, the present study utilized subjective measures of attentional control and affective arousal. The use of objective measures of attention and affective arousal would provide a more valid test of the role of attentional control in contamination aversion. ConclusionsThese findings suggest that attentional shifting abilities may serve as a vulnerability to affective arousal/regulation and behavioral avoidance of contaminants, but the latter relation only operated indirectly via disgust. These findings have clear implications for the etiology of contamination-related OCD.

The Nature, Assessment, and Treatment of Obsessive–Compulsive Disorder

Obsessive–compulsive disorder (OCD) is an anxiety disorder that affects between 1% to 2% of individuals and causes considerable impairment and disability. Although > 50% of individuals experience symptom onset in childhood, symptoms can continue to develop throughout adulthood. Accurate and timely assessment of clinical presentation is critical to limit impairment and improve prognosis. Presently, there are 2 empirically supported treatments available for OCD in children and adults, namely cognitive–behavioral therapy and pharmacotherapy with serotonin reuptake inhibitors. This article provides an introduction to the phenomenology, etiology, and clinical course of OCD. Assessment practices used to evaluate symptom severity are described, and evidence–based treatment options are reviewed, with appropriate distinctions drawn between children and adults. Finally, recommendations for assessment and treatment practices for OCD are explicated.

P-808 - The interaction between comt and BDNF variants influences obsessive-compulsive-related dysfunctional beliefs

Contemporary cognitive models emphasize the importance of certain dysfunctional beliefs in the development and maintenance of Obsessive-Compulsive Disorder (OCD): overimportance of thoughts, need to control thoughts, perfectionism, intolerance of uncertainty, inflated responsibility, and overestimation of threat. Although a recent twin study suggests that these dysfunctional beliefs are significantly heritable, there have been no previous attempts to analyze candidate genes associated with them. Our study aimed to investigate the possible association between OC-related dysfunctional beliefs and variants of two functional polymorphisms of the COMT (Val158Met) and BDNF (Val66Met) genes in 141 OCD patients. The non-synonymous mutation Val158Met (rs4680) in the COMT gene and the Val66Met functional variant (rs6265) in the BDNF gene were genotyped with the KASPar assay system. The validated Spanish short version of the Obsessive Beliefs Questionnaire, (OBQ-44), was used to assess dysfunctional beliefs. Multivariate analysis of covariance (MANCOVA) and a post hoc one-way analysis of covariance (ANCOVA) were perfomed. Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype when examining the two genes in isolation, but we detected a significant COMT x BDNF interaction effect on responsibility and overestimation of threat scores. These cognitive distortions were significantly higher among OCD subjects with the BDNF Met-present genotype who were also carriers of the COMT Val/Met and Met/Met genotypes. Our data suggest that an interaction between dopaminergic and neurotrophic functional gene variants influences some of the dysfunctional belief domains hypothesized to contribute to the etiology of OCD.

Postpartum Obsessive‐Compulsive Disorder

To synthesize the extant literature on the prevalence, phenomenology, etiology and treatment of postpartum obsessive-compulsive disorder (OCD). A discussion of differential diagnosis between postpartum OCD and other postpartum psychiatric conditions (e.g., depression, psychosis) and nonpostpartum-onset OCD is provided. All studies addressing postpartum OCD between the years 1950 and 2011 were reviewed. Data from all pertinent studies was explored as it related to postpartum OCD. Studies were organized based on their empirical technique (e.g., retrospective, prospective), population studied (e.g., clinical OCD, nonclinical populations, males), and etiological or treatment theory (e.g., cognitive-behavioral). The prevalence, phenomenology, etiology, and treatment of postpartum OCD are reviewed. The limited data on treatment approaches and outcomes for postpartum OCD are highlighted with a discussion of the role of nurses in the prevention and identification of postpartum OCD.

The role of glutamate signaling in the pathogenesis and treatment of obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is a common and often debilitating neuropsychiatric condition characterized by persistent intrusive thoughts (obsessions), repetitive ritualistic behaviors (compulsions) and excessive anxiety. While the neurobiology and etiology of OCD has not been fully elucidated, there is growing evidence that disrupted neurotransmission of glutamate within corticalstriatal–thalamocortical (CSTC) circuitry plays a role in OCD pathogenesis. This review summarizes the findings from neuroimaging, animal model, candidate gene and treatment studies in the context of glutamate signaling dysfunction in OCD. First, studies using magnetic resonance spectroscopy are reviewed demonstrating altered glutamate concentrations in the caudate and anterior cingulate cortex of patients with OCD. Second, knockout mouse models, particularly the DLGAP3 and Sltrk5 knockout mouse models, display remarkably similar phenotypes of compulsive grooming behavior associated with glutamate signaling dysfunction. Third, candidate gene studies have identified associations between variants in glutamate system genes and OCD, particularly for SLC1A1 which has been shown to be associated with OCD in five independent studies. This converging evidence for a role of glutamate in OCD has led to the development of novel treatment strategies involving glutamatergic compounds, particularly riluzole and memantine. We conclude the review by outlining a glutamate hypothesis for OCD, which we hope will inform further research into etiology and treatment for this severe neuropsychiatric condition.

Obsessive-Compulsive Disorder After Right Temporal-Lobe Hemorrhage

Back to table of contents Previous article Next article LettersFull AccessObsessive-Compulsive Disorder After Right Temporal-Lobe HemorrhageAbhishek Rai, MBBS, Amit Chopra, M.D., and Piyush Das, M.D.Abhishek RaiSearch for more papers by this author, MBBS, Amit ChopraSearch for more papers by this author, M.D., and Piyush DasSearch for more papers by this author, M.D.Published Online:1 Oct 2011https://doi.org/10.1176/jnp.23.4.jnpe13AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Obsessive-compulsive disorder (OCD) is a psychiatric illness characterized by persistent, intrusive, and senseless thoughts (obsessions) and urges to perform repetitive behaviors (compulsions) that interfere with functioning and/or cause distress. Although OCD secondary to various neurological lesions has been described, cerebral hemorrhage has rarely been associated with OCD. We present the first reported patient; this was a 40-year-old woman who developed OCD that responded successfully to high-dose selective serotonin reuptake inhibitor (SSRI) treatment after right temporal-lobe hemorrhage.Case Report“Mrs. X” was a 40-year-old woman with a medical history significant for frontoparietal hematoma resection during infancy, centroparietal epilepsy (stable on Depakote and levetiracetam), and depression, who presented to psychiatric clinic for gradually worsening obsessions and compulsion to shop (of 7 months' duration), with onset after right temporal-lobe hemorrhage (confirmed by brain imaging). Her depression, previously well controlled on citalopram 20 mg/day, had worsened to a moderately severe depression (Patient Health Questionnaire-9/PHQ-9 Score: 15), and her mild obsessive traits had worsened to distressing obsessions and compulsions to shop, meeting DSM-IV criteria for diagnosis of OCD. The compulsive shopping significantly reduced her anxiety. Other potential causes of her presentation, including worsening of seizure disorder, psychotic disorder, impulse-control disorder, mania, and substance abuse were ruled out. Although a citalopram dose increase to 40 mg daily led to remission of her depression (PHQ-9 score: 3), she continued to endorse compulsions to shop, to the extent that she ended up calling a realtor to buy a house. A gradual increase in citalopram dosage to 80 mg/day led to a 90% improvement in her OCD symptoms, and a further increase, to 100 mg/day, resulted in complete remission at 1-year follow-up. She had regular follow-up with her neurologist in the interim, with no suggestion of worsening of her seizure disorder by high-dose citalopram.DiscussionOCD has been associated with various neurological lesions, including traumatic brain injury, tumors, and infarcts, localized mainly to the frontal cortex and basal ganglia.1 The association of OCD with temporal-lobe epilepsy (TLE) seems strong, as 10%–20% of TLE patients suffer from OCD.2 Our case suggests temporal-lobe hemorrhage as a novel putative cause of OCD. Although there is no known overt locus of neuronal degeneration in OCD, functional-imaging studies suggest an abnormal metabolic activity in orbitofrontal cortex (OFC), anterior cingulate/caudal medial prefrontal cortex, and caudate nucleus.3 The OFC–subcortical circuit, referred to as the “OCD circuit,” projects from OFC to the ventral portion of caudate nucleus. OFC receives both afferent and efferent projections from the temporal lobe,4 which may underlie temporal lobe involvement in causation of OCD. Our patient's response to high-dose SSRI is plausible, considering the fact that serotonin acts on the “OCD circuit” by modulating 5HT3 receptors predominantly present in ventral striatum.5 Besides highlighting a novel mechanism of causation of OCD, we suggest that OCD associated with temporal lobe hemorrhage may be responsive to high-dose SSRI treatment.Dept. of Psychiatry and Psychology Mayo Clinic Rochester, MNCorrespondence: das.[email protected]edu; gen.[email protected]com1. Etcharry-Bouyx F , Dubas F : Obsessive-compulsive disorders associated with focal brain lesions, in: Behaviours and Mood Disorders in Focal Brain Lesions. Edited by Bogousslavsky JCummings J. Cambridge, UK, Cambridge University Press, 2000, pp 304–326Crossref, Google Scholar2. Kaplan PW : Epilepsy and obsessive-compulsive disorder. Dial Clin Neurosci 2010; 12:241–248Medline, Google Scholar3. Graybiel A , Rauch S : Toward a neurobiology of obsessive-compulsive disorder. Neuron 2000; 28:343–347Crossref, Medline, Google Scholar4. Cummings JL : Anatomic and behavioral aspects of frontal-subcortical circuits. Ann N Y Acad Sci 1995; 769:1–13Crossref, Medline, Google Scholar5. Marsden CA : The neuropharmacology of serotonin in central nervous system, in Selective Serotonin Reuptake Inhibitors. Edited by Feighner JPBoyer WF. New York, Wiley, 1991, pp 11–35Google Scholar FiguresReferencesCited byDetailsCited By“Need to Know” or the Strong Urge to Find Names of Unique Entities in Acquired Obsessive-Compulsive DisorderCognitive and Behavioral Neurology, Vol. 32, No. 2Journal of Stroke and Cerebrovascular Diseases, Vol. 28, No. 4Psychiatry and Clinical Psychopharmacology, Vol. 28, No. 3Journal of Neurotrauma, Vol. 32, No. 7Multivariate pattern analysis of DTI reveals differential white matter in individuals with obsessive‐compulsive disorder18 September 2013 | Human Brain Mapping, Vol. 35, No. 6Neuroscience & Biobehavioral Reviews, Vol. 37, No. 3 Volume 23Issue 4 Fall 2011Pages E13-E13 Metrics PDF download History Published online 1 October 2011 Published in print 1 October 2011

Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD

Obsessive compulsive disorder (OCD) has a complex etiology that encompasses both genetic and environmental factors. However, to date, despite the identification of several promising candidate genes and linkage regions, the genetic causes of OCD are largely unknown. The objective of this study was to conduct linkage studies of childhood-onset OCD, which is thought to have the strongest genetic etiology, in several OCD-affected families from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The authors used parametric and non-parametric approaches to conduct genome-wide linkage analyses using 5,786 single nucleotide repeat polymorphisms (SNPs) in three CVCR families with multiple childhood-onset OCD-affected individuals. We identified areas of suggestive linkage (LOD score ≥ 2) on chromosomes 1p21, 15q14, 16q24, and 17p12. The strongest evidence for linkage was on chromosome 15q14 (LOD = 3.13), identified using parametric linkage analysis with a recessive model, and overlapping a region identified in a prior linkage study using a Caucasian population. Each CVCR family had a haplotype that co-segregated with OCD across a ~7 Mbp interval within this region, which contains 18 identified brain expressed genes, several of which are potentially relevant to OCD. Exonic sequencing of the strongest candidate gene in this region, the ryanodine receptor 3 (RYR3), identified several genetic variants of potential interest, although none co-segregated with OCD in all three families. These findings provide evidence that chromosome 15q14 is linked to OCD in families from the CVCR, and supports previous findings to suggest that this region may contain one or more OCD susceptibility loci.

Trastorno obsesivo-compulsivo secundario a lesión frontal en traumatismo craneoencefálico

Introduction Traumatic brain injuries have been documented as a cause of obsessive-compulsive disorder (OCD). The risk of developing OCD may be slightly higher among people who suffer a traumatic brain injury (TBI). Case report We describe the case of a 23 year-old man who 12 months after TBI suffers from cognitive impairment, lack of impulse control, emotional psychopathology, obsessive, and specially compulsive symptoms. He meets criteria for ICD-10 diagnosis of OCD. Discussion Compulsive symptoms in this patient are consistent with those most frequently documented after TBI in previous literature. As in the present case, the frontal cortex, temporal and occipital lobes have been described as some of the involved damaged areas. There is high likelihood that the lesions we can see in the computerized tomography are responsible for the OCD we describe.

Association of catechol‐O‐methyl transferase (COMT) gene −287A/G polymorphism with susceptibility to obsessive–compulsive disorder in Chinese Han population

Several studies suggested a genetic component in the etiology of obsessive-compulsive disorder (OCD). COMT involves in the degradation of dopamine and norepinephrin. As another functional SNP locus, COMT -287A/G polymorphism showed an effect on enzyme activity, suggesting that it may influence brain dopamine levels. To identify association of COMT -287A/G polymorphism with susceptibility to OCD in Chinese Han population. We evaluate the genetic contribution of the COMT -287A/G polymorphism in 200 OCD patients and 403 OCD-free control of Chinese Han population by PCR-RFLP. In addition, we investigate whether COMT -287A/G polymorphism is associated with one or more of these symptom dimensions or other characteristics such as sex, age of onset, and tic-relatedness and evaluate the association of the factorial structure of OCD symptoms from the Y-BOCS checklist with the COMT -287A/G polymorphism. A statistical difference was found in the genotypic frequencies of COMT -287A/G between the OCD and control groups (χ(2) = 13.99, DF = 2, P = 0.00091) and in the genotypic frequencies of GG genotype versus AA and AG genotypes of COMT -287 (χ(2) = 13.49, DF = 1, P = 0.00024, OR = 3.43, 95% CI = 1.78-6.62). There was a trend for an association in the genotypic distributions of COMT -287A/G polymorphism of males (χ(2) = 27.81; DF = 2; P < 0.001) and females (χ(2) = 7.31; DF = 2; P = 0.026) between the OCD patients and the controls. Using principal component analysis, we derived 5 factors from 12 main contents of OCD symptoms from the Y-BOCS checklist and found no association with COMT -287A/G polymorphism. Our study supports the involvement of the COMT -287A/G polymorphism in the genetic susceptibility to OCD in Chinese Han population.

Obsessive-Compulsive Disorder After Right Temporal-Lobe Hemorrhage

Back to table of contents Previous article Next article LettersFull AccessObsessive-Compulsive Disorder After Right Temporal-Lobe HemorrhageAbhishek Rai, MBBS, Amit Chopra, M.D., and Piyush Das, M.D.Abhishek RaiSearch for more papers by this author, MBBS, Amit ChopraSearch for more papers by this author, M.D., and Piyush DasSearch for more papers by this author, M.D.Published Online:1 Oct 2011https://doi.org/10.1176/jnp.23.4.jnpe13AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Obsessive-compulsive disorder (OCD) is a psychiatric illness characterized by persistent, intrusive, and senseless thoughts (obsessions) and urges to perform repetitive behaviors (compulsions) that interfere with functioning and/or cause distress. Although OCD secondary to various neurological lesions has been described, cerebral hemorrhage has rarely been associated with OCD. We present the first reported patient; this was a 40-year-old woman who developed OCD that responded successfully to high-dose selective serotonin reuptake inhibitor (SSRI) treatment after right temporal-lobe hemorrhage.Case Report“Mrs. X” was a 40-year-old woman with a medical history significant for frontoparietal hematoma resection during infancy, centroparietal epilepsy (stable on Depakote and levetiracetam), and depression, who presented to psychiatric clinic for gradually worsening obsessions and compulsion to shop (of 7 months' duration), with onset after right temporal-lobe hemorrhage (confirmed by brain imaging). Her depression, previously well controlled on citalopram 20 mg/day, had worsened to a moderately severe depression (Patient Health Questionnaire-9/PHQ-9 Score: 15), and her mild obsessive traits had worsened to distressing obsessions and compulsions to shop, meeting DSM-IV criteria for diagnosis of OCD. The compulsive shopping significantly reduced her anxiety. Other potential causes of her presentation, including worsening of seizure disorder, psychotic disorder, impulse-control disorder, mania, and substance abuse were ruled out. Although a citalopram dose increase to 40 mg daily led to remission of her depression (PHQ-9 score: 3), she continued to endorse compulsions to shop, to the extent that she ended up calling a realtor to buy a house. A gradual increase in citalopram dosage to 80 mg/day led to a 90% improvement in her OCD symptoms, and a further increase, to 100 mg/day, resulted in complete remission at 1-year follow-up. She had regular follow-up with her neurologist in the interim, with no suggestion of worsening of her seizure disorder by high-dose citalopram.DiscussionOCD has been associated with various neurological lesions, including traumatic brain injury, tumors, and infarcts, localized mainly to the frontal cortex and basal ganglia.1 The association of OCD with temporal-lobe epilepsy (TLE) seems strong, as 10%–20% of TLE patients suffer from OCD.2 Our case suggests temporal-lobe hemorrhage as a novel putative cause of OCD. Although there is no known overt locus of neuronal degeneration in OCD, functional-imaging studies suggest an abnormal metabolic activity in orbitofrontal cortex (OFC), anterior cingulate/caudal medial prefrontal cortex, and caudate nucleus.3 The OFC–subcortical circuit, referred to as the “OCD circuit,” projects from OFC to the ventral portion of caudate nucleus. OFC receives both afferent and efferent projections from the temporal lobe,4 which may underlie temporal lobe involvement in causation of OCD. Our patient's response to high-dose SSRI is plausible, considering the fact that serotonin acts on the “OCD circuit” by modulating 5HT3 receptors predominantly present in ventral striatum.5 Besides highlighting a novel mechanism of causation of OCD, we suggest that OCD associated with temporal lobe hemorrhage may be responsive to high-dose SSRI treatment.Dept. of Psychiatry and Psychology Mayo Clinic Rochester, MNCorrespondence: das.[email protected]edu; gen.[email protected]com1. Etcharry-Bouyx F , Dubas F : Obsessive-compulsive disorders associated with focal brain lesions, in: Behaviours and Mood Disorders in Focal Brain Lesions. Edited by Bogousslavsky JCummings J. Cambridge, UK, Cambridge University Press, 2000, pp 304–326Crossref, Google Scholar2. Kaplan PW : Epilepsy and obsessive-compulsive disorder. Dial Clin Neurosci 2010; 12:241–248Medline, Google Scholar3. Graybiel A , Rauch S : Toward a neurobiology of obsessive-compulsive disorder. Neuron 2000; 28:343–347Crossref, Medline, Google Scholar4. Cummings JL : Anatomic and behavioral aspects of frontal-subcortical circuits. Ann N Y Acad Sci 1995; 769:1–13Crossref, Medline, Google Scholar5. Marsden CA : The neuropharmacology of serotonin in central nervous system, in Selective Serotonin Reuptake Inhibitors. Edited by Feighner JPBoyer WF. New York, Wiley, 1991, pp 11–35Google Scholar FiguresReferencesCited byDetailsCited by“Need to Know” or the Strong Urge to Find Names of Unique Entities in Acquired Obsessive-Compulsive DisorderCognitive and Behavioral Neurology, Vol. 32, No. 2Journal of Stroke and Cerebrovascular Diseases, Vol. 28, No. 4Psychiatry and Clinical Psychopharmacology, Vol. 28, No. 3Journal of Neurotrauma, Vol. 32, No. 7Multivariate pattern analysis of DTI reveals differential white matter in individuals with obsessive‐compulsive disorder18 September 2013 | Human Brain Mapping, Vol. 35, No. 6Neuroscience & Biobehavioral Reviews, Vol. 37, No. 3 Volume 23Issue 4 Fall 2011Pages E13-E13 Metrics PDF download History Published online 1 October 2011 Published in print 1 October 2011

Investigating SAPAP3 variants in the etiology of obsessive-compulsive disorder and trichotillomania in the South African white population

Background Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by repeated obsessions and compulsions. Trichotillomania (TTM), a psychiatric disorder characterized by repetitive hairpulling, is presently classified as an impulse control disorder, but has also been viewed as an obsessive-compulsive spectrum disorder. Both conditions are complex disorders, with evidence from family and twin studies indicating that their etiology includes a genetic component. Results from a recent knockout animal model suggest that SAP90/PSD95-associated protein 3 (SAPAP3) may be involved in the pathophysiology of both disorders. Methods Seven polymorphic variants distributed across the gene encoding SAPAP3 were genotyped in South African white OCD (n = 172), TTM (n = 45), and control (n = 153) subjects. Single-locus and haplotype analyses were conducted to determine association between genetic variants and subjects with OCD, TTM, and controls. Results Although single-locus analysis revealed a significant association between rs11583978 in SAPAP3 and TTM, this association was nonsignificant after correction for multiple testing. In the OCD group, a significant association was observed between earlier age at onset and the A-T-A-T (rs11583978-rs7541937-rs6662980-rs4652867) haplotype compared with the C-G-G-G haplotype. Conclusions This study generated preliminary evidence to link SAPAP3 variants to the development of earlier onset OCD. Future studies should concentrate on locating the susceptibility variant(s) by focusing on functional polymorphisms within SAPAP3.

Development and initial validation of the obsessive belief questionnaire-child version (OBQ-CV)

Cognitive models of obsessive-compulsive disorder (OCD) propose that beliefs are important in the etiology and maintenance of OCD and that these beliefs develop during childhood [Neal et al., 1991: Psychol Bull 109:400-410; Rachman, 1997: Behav Res Ther 35:793-802; Cronbach, 1951: Psychometrika 16:297-334]. However, the ability to test these predictions has been hampered by the lack of a standardized measure of OCD-related beliefs for youth. Therefore, this article presents initial data on a youth version of the widely used Obsessive Belief Questionnaire (OBQ) [Bonett, 2002: J Educ Behav Stat 27:335-340]. Data examining the psychometric properties of the Obsessive Belief Questionnaire-Child Version (OBQ-CV) are presented from two pediatric OCD samples: a North American (n=29, aged 9-17 years) and a Dutch sample (n=48, aged 8-18 years). Preliminary findings from both samples support the internal consistency, retest reliability, and convergent validity of the OBQ-CV. Results of this study suggest that the OBQ-CV is a promising tool for examining the role of cognitions in pediatric OCD. Development of the OBQ-CV to augment the existing adult version of the scale creates unique opportunities for investigating the role of cognitions in OCD across the lifespan.