Genetic meta‐analysis of obsessive–compulsive disorder and self‐report compulsive symptoms

We investigated whether obsessive–compulsive (OC) symptoms from a population‐based sample could be analyzed to detect genetic variants influencing obsessive–compulsive disorder (OCD). We performed a genome‐wide association studies (GWAS) on the obsession (rumination and impulsions) and compulsion (checking, washing, and ordering/precision) subscales of an abbreviated version of the Padua Inventory (N = 8,267 with genome‐wide genotyping and phenotyping). The compulsion subscale showed a substantial and significant positive genetic correlation with an OCD case–control GWAS (r _G = 0.61, p = .017) previously published by the Psychiatric Genomics Consortium (PGC‐OCD). The obsession subscale and the total Padua score showed no significant genetic correlations (r _G = ?0.02 and r _G = 0.42, respectively). A meta‐analysis of the compulsive symptoms GWAS with the PGC‐OCD revealed no genome‐wide significant Single‐Nucleotide Polymorphisms (SNPs combined N = 17,992, indicating that the power is still low for individual SNP effects). A gene‐based association analysis, however, yielded two novel genes (WDR7 and ADCK1). The top 250 genes in the gene‐based test also showed a significant increase in enrichment for psychiatric and brain‐expressed genes. S‐Predixcan testing showed that for genes expressed in hippocampus, amygdala, and caudate nucleus significance increased in the meta‐analysis with compulsive symptoms compared to the original PGC‐OCD GWAS. Thus, the inclusion of dimensional symptom data in genome‐wide association on clinical case–control GWAS of OCD may be useful to find genes for OCD if the data are based on quantitative indices of compulsive behavior. SNP‐level power increases were limited, but aggregate, gene‐level analyses showed increased enrichment for brain‐expressed genes related to psychiatric disorders, and increased association with gene expression in brain tissues with known emotional, reward processing, memory, and fear‐formation functions.     

Obsessive‐Compulsive Disorder in the DSM‐5

Whereas the specific diagnostic criteria for obsessive‐compulsive disorder (OCD) have changed in only minor ways in the transition from DSM‐IV to DSM‐5, a more substantial change is that OCD is no longer classified as an anxiety disorder. Rather, it is now the flagship diagnosis of a new diagnostic category: the obsessive‐compulsive and related disorders (OCRDs). In this article, we describe the nature of obsessional problems as determined through empirical research before turning to a consideration of how OCD is defined in previous editions of the DSM and in DSM‐5. We then critically consider the DSM criteria, as well as the basis for removing OCD from the anxiety disorders and creating the new OCRD category. Finally, we consider the implications of these changes for clinical practice and research on OCD.     

Association of the tumor necrosis factor ‐308 A/G promoter polymorphism with Tourette syndrome

Several lines of evidence suggest that certain subtypes of obsessive‐compulsive and tic disorders might be paediatric manifestations of post‐streptococcal autoimmunity caused by cross‐reactive autoantibodies. As tumor necrosis factor (TNF) is known to play a seminal role in coordinating the humoral immune response, TNF gene polymorphisms have been proposed as genetic risk factors both in obsessive‐compulsive disorder (OCD) and Tourette syndrome (TS). The aim of this study was to investigate two TNF promoter polymorphisms (‐238 A/G: rs361525 and ‐308 A/G: rs1800629) on the genetic susceptibility to OCD and TS in a child psychiatric sample (102 patients with OCD and 117 patients with TS). In the case–control set‐up, the genotype and allele frequencies were compared to a control group from the general population (n = 405). As a control child psychiatric sample, 194 children with attention‐deficit hyperactivity disorder were also genotyped. Our results revealed that the TNF ‐308 G‐allele was more frequent in children with TS compared to controls (90.2% vs 84.8%, P = 0.037). For confirmation of this genetic association, a family‐based analysis, the transmission disequilibrium test was used, which showed preferential transmission of the G‐allele to patients with TS (nominal P‐value 0.011). Moreover, this allele was also transmitted more frequently to children with tic symptoms (nominal P‐value 0.039). No association was found between OCD or obsessive‐compulsive symptoms and the studied TNF polymorphisms. Based on these findings, the TNF ‐308 G‐allele can be associated with Tourette syndrome, highlighting the potential pathophysiological role of TNF dysregulation.     

Compulsive behaviours and levels of belief in obsessive–compulsive disorder: a case‐series analysis of their interrelationships

This study examined interrelationships of changes in compulsive behaviours and two levels of belief over treatment of obsessive–compulsive disorder (OCD). Levels were individual‐specific obsessive beliefs (termed here manifest beliefs) and OCD‐relevant general beliefs. If OCD‐relevant general beliefs are functionally linked to manifest beliefs and compulsive behaviours, changes in compulsive behaviours and both belief types should occur mostly in tandem, even if only one or two of these three elements are explicitly targeted. Baselines consisting of time performing compulsive behaviours, strength of manifest belief and strength of OCD‐relevant general beliefs were monitored daily by six participants over three phases in an A/B/B + C design. (A = no treatment, B = exposure/response prevention and C = cognitive therapy targeting only OCD‐relevant general beliefs.) Changes in compulsive behaviours, manifest beliefs and OCD‐relevant general beliefs moved primarily in tandem over treatment phases, suggesting functional links between these elements. Copyright © 2006 John Wiley & Sons, Ltd.     

Obsessive beliefs and their relation to obsessive–compulsive symptoms

Relationships between obsessive–compulsive symptoms and beliefs identified as relevant to obsessive–compulsive disorder (OCD) are investigated among university students and a small clinical sample. One hundred and fifty‐four participants completed measures of OCD‐related beliefs, OCD symptoms, and anxiety and depression symptoms. Results showed that belief domains were strongly interrelated and were not sufficiently separate to use individually in further analysis. The summed obsessive beliefs score was significantly correlated with all measured obsessional symptom subtypes, after controlling for anxiety and depression. Possible explanations and clinical implications of the results are discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

Not just thinking,but believing: Obsessive beliefs and domains of cognitive fusion in the prediction of OCD symptom dimensions

Cognitive fusion (CF) involves the tendency to “buy in” to thoughts and feelings and consists of three empirically established domains: somatic concerns, emotion regulation, and negative evaluation. CF is hypothesized to play a role in obsessive–compulsive disorder (OCD). The present study examined how well the CF domains, relative to traditional cognitive–behavioural constructs (i.e., obsessive beliefs such as inflated responsibility), predict OCD symptoms. Fifty‐two treatment‐seeking adults with OCD completed self‐report measures of CF, obsessive beliefs, OCD symptoms, and general distress. Domains of CF were differentially associated with the responsibility for harm, symmetry, and unacceptable thoughts of OCD dimensions; yet after accounting for obsessive beliefs, only the negative evaluation domain of CF significantly predicted symmetry OCD symptoms. Obsessive beliefs significantly predicted all OCD dimensions except for contamination. These findings provide additional support for existing cognitive–behavioural models of OCD across symptom dimensions, with the exception of contamination symptoms, and suggest that the believability of thoughts and feelings about negative evaluation adds to the explanation of symmetry symptoms. Conceptual and treatment implications, study limitations, and future directions are discussed.     

Obsessional beliefs,compulsive behaviours and symptom severity: their evolution and interrelation over stages of treatment

The current study reports a case series examining (1) the variation in strength of obsessional doubt and belief in consequences of the doubt; and (2) the interaction between these cognitive components and symptom measures of duration and severity of obsessive–compulsive disorder (OCD), over 24 weeks of cognitive behaviour therapy. Eight participants diagnosed with OCD, four with contamination‐related rituals and four with checking behaviours, were selected on the basis of the Yale–Brown obsessive–compulsive scale (Y‐BOCS) and Padua ratings. All participants completed daily diaries measuring strength of principal obsessional doubt (0–100), strength of belief in consequences of the doubt (0–100) and the duration of the compulsive rituals throughout the 24 weeks of therapy. Severity of symptomatology was measured pre‐ and post‐treatment using the Y‐BOCS. Change in all measures was analysed over time following the procedure outlined by Storchheim and O'Mahoney (2006). Results showed that decrease in belief in secondary consequences is always accompanied by a decrease in strength of obsessions, but the converse does not hold. Furthermore, change in OCD symptomatology may precede cognitive changes. Copyright © 2008 John Wiley & Sons, Ltd.     

Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder

The distribution of obsessive compulsive symptoms was compared in 16 individuals with primary obsessive compulsive disorder (OCD) and 16 individuals with Gilles de la Tourette syndrome (GTS) and associated obsessive compulsive behaviors (OCB). The two groups showed significant differences in the distribution of OC symptomatology. Furthermore, those OCD probands who shared a similar symptom profile with GTS individuals all had a positive family history of OCD. All of the other OCD probands were isolated cases. Implications of this finding on the etiology and pathogenesis of the two disorders are discussed. Am. J. Med. Genet. 74:432–438, 1997. © 1997 Wiley-Liss, Inc.     

Validation of the Serbian version of the Metacognitions Questionnaire‐30 in nonclinical and clinical samples

The Metacognitions Questionnaire (MCQ‐30) is a brief multidimensional measure used for assessment of metacognitive beliefs in psychopathology. The aim of this study was to assess the psychometric properties of MCQ‐30 in Serbian nonclinical (n = 246) and clinical (n = 171; anxiety and depressive disorders) samples. The reliability of the questionnaire and its subscales was satisfactory. An exploratory factor analysis yielded a five‐factor solution in both groups, whereas a confirmatory factor analysis showed a somewhat weaker fit of the model. The MCQ‐30 showed positive associations with measures of anxiety, pathological worry, depressive, and obsessive–compulsive symptoms in both samples, demonstrating adequate convergent validity. The instrument was sensitive to differences in metacognitive beliefs between nonclinical and clinical samples. MCQ‐30 subscales showed incremental contributions in predicting pathological worry after controlling for the variance in obsessive–compulsive symptoms and vice versa. Our results suggest that the MCQ‐30 is a reliable and valid instrument for assessing metacognitive beliefs in both nonclinical and clinical samples. Moreover, the findings support the use of the MCQ‐30 in Serbian population and extend support for the metacognitive model.     

Thought‐action fusion and inflated responsibility beliefs in obsessive‐compulsive disorder

In obsessive‐compulsive disorder (OCD), inflated responsibility (IR) beliefs and thought‐action fusion (TAF) are two cognitive schema argued to contribute to obsessions and compulsions. We investigated whether IR and TAF are OCD‐specific or whether they occur in other anxiety disorders. Adults diagnosed with OCD (n = 20) or other anxiety disorders (n = 21), and non‐clinical controls (n = 22) completed measures of OCD symptomatology and severity, TAF, appraisals and interpretations of responsibility, and depression. IR was more prominent in those with OCD as compared with those with other anxiety disorders, with correlational analyses confirming that a high sense of personal responsibility was associated with high levels of obsessionality even after controlling for depression. No group differences, however, emerged between the clinical groups on measures of TAF, both groups showing elevated TAF compared with controls. Indeed, TAF and obsessional symptoms were correlated only in the presence of negative affect. These results suggest that although IR may be higher in those with OCD compared with other anxiety disorders, TAF is not specific to OCD. Results are discussed in the context of cognitive appraisal models of OCD.     

Obsessive–compulsive disorder beliefs,metacognitive beliefs and obsessional symptoms: relations between parent beliefs and child symptoms

Investigations of obsessive–compulsive disorder (OCD) have increasingly emphasized the role of cognition in symptom development and maintenance. In the present study, relationships between parent and adolescent child OCD symptoms and OCD cognition measures were explored to elucidate how OCD related beliefs and OCD symptoms might develop. One hundred and twenty‐six non‐clinical parent–adolescent pairs completed measures of OCD symptoms, OCD related beliefs and metacognitive beliefs (cognitive self‐consciousness [CSC], the tendency to focus attention on thought processes). A significant indirect relationship was found between parent OCD symptoms and adolescent OCD symptoms through specific adolescent OCD related beliefs. Contrary to expectations, parent and adolescent CSC were not correlated. Although findings were limited by the correlational and cross‐sectional design, implications of the observed associations for theory and treatment are discussed. Copyright © 2006 John Wiley & Sons, Ltd.     

Self‐compassion and emotion regulation difficulties in obsessive–compulsive disorder

Lack of self‐compassion and deficits in emotion regulation are associated with various psychopathological symptoms and may play a role in the development and maintenance of obsessive–compulsive disorder (OCD). However, further empirical research is still needed to better understand these constructs in the context of this disorder. The present study investigated the relation between self‐compassion, emotion regulation difficulties, obsessive beliefs, and obsessive–compulsive symptom severity in 90 patients with OCD using self‐report questionnaires. Symptom severity and obsessive beliefs were negatively correlated to self‐compassion and positively associated with emotion regulation difficulties. Additionally, self‐compassion showed a negative relation to emotion regulation difficulties. Emotion regulation difficulties—but not self‐compassion—predicted symptom severity when controlling for obsessive beliefs and depression in a hierarchical regression analysis. Further analyses showed that emotion regulation deficits mediated the relationship between self‐compassion and OCD symptom severity. Our results provide preliminary evidence that targeting self‐compassion and putting more emphasis on emotion regulation deficits might be promising treatment approaches for patients with OCD. Future studies could investigate which specific interventions that directly address these variables improve treatment outcome.     

Chronic medication does not affect hyperactive error responses in obsessive‐compulsive disorder

Patients with obsessive‐compulsive disorder (OCD) show an increased error‐related negativity (ERN), yet previous studies have not controlled for medication use, which may be important given evidence linking performance monitoring to neurotransmitter systems targeted by treatment, such as serotonin. In an examination of 19 unmedicated OCD patients, 19 medicated OCD patients, 19 medicated patient controls without OCD, and 21 unmedicated healthy controls, we found greater ERNs in OCD patients than in controls, irrespective of medication use. Severity of generalized anxiety and depression was associated with ERN amplitude in controls but not patients. These data confirm previous findings of an exaggerated error response in OCD, further showing that it cannot be attributed to medication. The absence in patients of a relationship between ERN amplitude and anxiety/depression, as was found in controls, suggests that elevated error signals in OCD may be disorder‐specific.     

Mental health problems in adolescents with delayed sleep phase: results from a large population‐based study in Norway

The aim of the current study was to compare mental health problems, resilience and family characteristics in adolescents with and without delayed sleep phase (DSP) in a population‐based sample. Data were taken from the youth@hordaland‐survey, a large population‐based study in Hordaland County in Norway conducted in 2012. In all, 9338 adolescents aged 16–19 years (53.5% girls) provided self‐reported data on a wide range of instruments assessing mental health symptoms, including depression, anxiety, obsessive–compulsive behaviours, attention deficit hyperactive disorder (ADHD) symptoms, perfectionism, resilience and sleep. Measures of socioeconomic status were also included. Three hundred and six adolescents (prevalence 3.3%) were classified as having DSP [according to the International Classification of Sleep Disorders‐2 (ICSD‐2)] criteria. Adolescents with DSP reported higher levels of depression, anxiety and ADHD symptoms. Adolescents with DSP also exhibited significantly lower levels of resilience. The Cohen's d effect sizes ranged from small [obsessive–compulsive disorder (OCD): d = 0.15] to moderate (inattention: d = 0.71). In the fully adjusted model, the significant predictors of DSP included inattention [odds ratio (OR): 2.11], lack of personal structure (OR: 2.07), low (OR: 1.85) and high (OR: 1.91) paternal education, parents not living together (OR: 1.81), hyperactivity/inattention (OR: 1.71) and poorer family economy (OR: 1.59). In conclusion, the high symptom load across a range of mental health measures suggests that a broad and thorough clinical approach is warranted when adolescents present with DSP.     

Associations of neural error-processing with symptoms and traits in a dimensional sample recruited across the obsessive–compulsive spectrum

The error-related negativity (ERN), a neural response to errors, has been associated with several forms of psychopathology and assumed to represent a neural risk marker for obsessive–compulsive disorder (OCD) and anxiety disorders. Yet, it is still unknown which specific symptoms or traits best explain ERN variation. This study investigated performance-monitoring in participants (N = 100) recruited across a spectrum of obsessive–compulsive characteristics (n = 26 patients with OCD; n = 74 healthy participants including n = 24 with low, n = 24 with medium, and n = 26 with high OC-characteristics). Several compulsivity- and anxiety-associated characteristics were assessed and submitted to exploratory principal axis factor analysis. Associations of raw measures and derived factors with ERN and correct-related negativity (CRN) were examined. Patients with OCD showed increased ERN amplitudes compared to healthy participants. The ERN was associated with a variety of traits related to anxiety and negative affect. Factor analysis results revealed a most prominent association of the ERN with a composite measure of anxiety and neuroticism, whereas the CRN was specifically associated with compulsivity. Results support differential associations for the ERN and CRN and demonstrate that a dimensional recruitment approach and use of composite measures can improve our understanding of characteristics underlying variation in neural performance monitoring.     

Parenting style and obsessive‐compulsive symptoms and personality traits in a student sample

There is widespread acceptance of the idea that aspects of parenting such as overprotectiveness and perfectionism contribute to the pathogenesis of obsessive‐compulsive disorder (OCD). Less resolved is whether the important dimensions of parenting are overprotectiveness, lack of acceptance, authoritarian style, discouragement of risk‐taking, and/or induction of guilt. It is also unclear whether different parenting characteristics are associated with the development of symptoms of OCD, compared to the traits of obsessive‐compulsive personality disorder (OCPD). OCD symptoms and OC personality traits were measured in a non‐clinical, student sample and correlated with students' report of parents' acceptance, disciplinary firmness, and psychological control (a construct which included psychological manipulation and guilt‐induction). Following the literature on both clinical and subclinical OCD and OCPD, we predicted that all three scales would correlate with OCD symptoms and OCPD traits. Stepwise regression analysis revealed that psychological control was the unique predictor, controlling for depressive symptoms. Unexpectedly, a controlling parenting style was not selectively associated with classical OC symptoms or OC personality traits. Rather, psychological control was associated with a broad‐spectrum of anxiety and depressive symptoms which cut across diagnostic boundaries. Findings are generally compatible with a single underlying vulnerability to both OCD and OCPD, as well as generalized/social anxiety and depressive symptoms, which can be shaped by cultural and familial factors to a specific clinical presentation. Copyright © 2002 John Wiley & Sons, Ltd.     

Dose meta‐cognition or responsibility predict obsessive–compulsive symptoms: a test of the metacognitive model

Cognitive models of Obsessive–Compulsive disorder (OCD) have emphasized inflated responsibility (Salkovskis, 1985), thought–action fusion (Rachman, 1993), and metacognitive beliefs (Wells, 1997; Wells & Matthews, 1994), as factors contributing to disorder. The metacognitive model views responsibility as a by‐product of metacognitions that make little additional contribution to OCD, and gives rise to the following hypotheses: (1) responsibility and meta‐cognitive beliefs are positively correlated with obsessive–compulsive symptoms, (2) the relationship between responsibility and obsessive–compulsive symptoms is statistically dependent on meta‐cognition, (3) meta‐cognitions positively correlate with obsessive–compulsive symptoms independently of responsibility. The results supported each of these hypotheses and exploratory analyses were conducted to find the best unique set of predictors among a range of metacognitive dimensions. Metacognitive beliefs concerning need to control thoughts, thought–action fusion, and negative beliefs about cognitive competence emerged as reliable predictors. An additional contribution was made by thought–event fusion in one equation. The results provide support for the meta‐cognitive model. Copyright © 2004 John Wiley & Sons, Ltd.     

Responsibility attitude,obsession and compulsion: further support in a non‐clinical sample

Responsibility is one of the most investigated constructs in obsessive‐compulsive disorder (OCD). Although there are an increasing number of studies on this topic, results seem to be questionable. Whereas several authors reported a significant link between OC behaviour and responsibility in nonclinical as well as in clinical samples, the findings of many authors failed to demonstrate the presence of such an association. In the current study, we examined the relationship between obsessive‐compulsive behaviour and responsibility. To this aim, participants filled in five inventories: the Responsibility Attitude Scale (RAS), the Responsibility Questionnaire (RQ), the Padua Inventory Revised (PI‐R), the State‐Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). Results showed a relationship between obsessive‐compulsive behaviour (PI‐R scores) and responsibility, as measured by both RAS and RQ. A principal component analysis showed that RAS can be interpreted as a four‐factor scale, accounting for 63% of the variance overall. Regression analyses showed that responsibility can be considered a significant predictor of obsession and compulsion behaviour, as measured by PI‐R. Furthermore, showing a connection between specific factors of responsibility and certain kinds of obsessive‐compulsive behaviour, results seem to confirm the hypothesis that responsibility is more salient in checking than in cleaning symptoms. Copyright © 2001 John Wiley & Sons, Ltd.     

Family‐based genetic association study of DLGAP3 in Tourette Syndrome

Tourette syndrome (TS) is a childhood‐onset neuropsychiatric disorder that is familial and highly heritable. Although genetic influences are thought to play a significant role in the development of TS, no definite TS susceptibility genes have been identified to date. TS is believed to be genetically related to both obsessive‐compulsive disorder (OCD) and grooming disorders (GD) such as trichotillomania (TTM). SAP90/PSD95‐associated protein 3 (SAPAP3/DLGAP3) is a post‐synaptic scaffolding protein that is highly expressed in glutamatergic synapses in the striatum and has recently been investigated as a candidate gene in both OCD and GD studies. Given the shared familial relationship between TS, OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a family‐based sample of 289 TS trios, 22 common single nucleotide polymorphisms (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations were identified between TS and rs11264126 and two haplotypes containing rs11264126 and rs12141243. Secondary analyses demonstrated that these results cannot be explained by the presence of comorbid OCD or TTM in the sample. Although none of these results remained significant after correction for multiple hypothesis testing, DLGAP3 remains a promising candidate gene for TS. © 2010 Wiley‐Liss, Inc.     

Is exposure and response prevention treatment for obsessive–compulsive disorder as aversive as we think?

Background: Meta‐analytical studies have confirmed that exposure and response prevention (ERP) is the psychological treatment of choice for obsessive–compulsive disorder (OCD). Anecdotal evidence suggests that patients drop out of ERP because of the aversive nature of the treatment. Methods: In this study, eight individuals diagnosed with OCD described their experience of ERP treatment in one‐to‐one semi‐structured interviews. Qualitative data analysis was used to identify common themes across participants. Results: Common themes were categorised into a) Experience of ERP, b) specific treatment factors, c) non‐specific treatment factors, and d) quality of life impact. Conclusions: Several specific and non‐specific variables emerged as significantly impacting on the experience of completing ERP. A number of important themes emerged that provide special areas for consideration for minimising distress to clients when treating OCD using ERP.