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.     

Sex differences in the genetic architecture of obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is a highly heritable complex phenotype that demonstrates sex differences in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome‐wide characterization of the sex‐specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sex differences including a sex‐dependent liability threshold, the presence of individual sex‐specific risk variants on the autosomes and the X chromosome, and sex‐specific pleiotropic effects. Furthermore, we tested the hypothesis that genetic heterogeneity between the sexes may obscure associations in a sex‐combined genome‐wide association study. We observed a strong genetic correlation between male and female OCD and no evidence for a sex‐dependent liability threshold model, suggesting that sex‐combined analysis does not suffer from widespread loss of power because of genetic heterogeneity between the sexes. While we did not detect any significant sex‐specific genome‐wide single nucleotide polymorphisms (SNP) associations, we did identify two significant gene‐based associations in females: GRID2 and GRP135, which showed no association in males. We observed that the SNPs with sexually differentiated effects showed an enrichment of regulatory variants influencing expression of genes in brain and immune tissues. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex‐specific genetic risk factors for OCD.     

Differences in clinical intrusive thoughts between obsessive–compulsive disorder,generalized anxiety disorder,and hypochondria

Differences and similarities between intrusive thoughts typical of obsessive–compulsive disorder, generalized anxiety disorder, and hypochondriasis are relevant for their differential diagnosis, formulation, and psychological treatment. Previous research in non‐clinical samples pointed out the relevance of some process variables, such as responsibility, guilt, or neutralization strategies. This research is aimed to investigate the differences and similarities between clinical obsessions, worries, and illness intrusions in some of these process variables. A second aim is to identify models based on these variables that could reliably differentiate between them. Three groups of patients with obsessive–compulsive disorder (n  = 35; 60% women, mean age 38.57), generalized anxiety disorder (n  = 36; 61.1% women, mean age 41.50), and hypochondriasis (n  = 34; 70.6% women, mean age 31.59) were evaluated using the Cognitive Intrusions Questionnaire—Transdiagnostic Version (Romero‐Sanchiz, Nogueira‐Arjona, Godoy‐Ávila, Gavino‐Lázaro, & Freeston, 2017 ). The results showed that some appraisals (e.g., responsibility or egodystonicity), emotions (e.g., guilt or insecurity), neutralization strategies, and other variables (e.g., verbal content or trigger from body sensation) are relevant for the discrimination between obsessions, worries, and illness intrusions. The results also showed 3 stable models based on these variables for the discrimination between these thoughts. The implication of these results in the diagnosis, formulation, and psychological treatment of obsessive–compulsive disorder, generalized anxiety disorder, and hypochondriasis is discussed.     

Continuity between DSM‐5 Section II and Section III personality traits for obsessive–compulsive personality disorder

Objective

Obsessive–compulsive personality disorder (OCPD) is formally operationalized in Section II of the DSM‐5 by a heterogeneous collection of 8 categorical criteria. Section III contains an alternative model operationalizing personality disorders via dimensional personality traits and associated impairment. The extent to which the personality traits used to define OCPD in Section III correspond with the Section II operationalization of the disorder is contested. The current study aims to contribute to the evidence base necessary to solidify the optimal trait profile for this disorder via a more fine‐tuned examination of OCPD.

Method

The research questions were examined using a clinical sample of 142 Danish adults who completed the Structured Clinical Interview for DSM‐IV Axis II Disorders and the Personality Inventory for DSM‐5 to index both the Sections II and III (personality traits) operationalizations of OCPD, respectively.

Results

Bivariate correlations supported Rigid Perfectionism and Perseveration as traits relevant to OCPD; however, hierarchical regression analyses indicated that of the 4 traits used in the Section III operationalization of OCPD, only Rigid Perfectionism uniquely predicted OCPD (p < .05). In addition to Rigid Perfectionism, the conceptually relevant traits of Submissiveness, Suspiciousness, and (low) Impulsivity were also found to uniquely predict OCPD and its specific symptoms in a regression model.

Conclusions

These findings indicate that the traits proposed in Section III are only partially aligned with the traditional, Section II conceptualization of OCPD, and may be augmented by incorporating Submissiveness, Suspiciousness, and (low) Impulsivity. In light of the current findings and existing literature, a modified constellation of traits to operationalize OCPD is likely justified.     

The role of feared possible selves in obsessive–compulsive and related disorders: A comparative analysis of a core cognitive self‐construct in clinical samples

Increasingly, cognitive‐behavioural models have been considering the role of beliefs about the self in the development and maintenance of obsessive–compulsive disorder (OCD), including sensitive domains of self‐concept and feared self‐perceptions. This has led to the development of the Fear of Self Questionnaire (FSQ; Aardema et al., 2013 ), which has shown strong internal consistency, divergent and convergent validity, and found to be a major predictor of unwanted thoughts and impulses (i.e., repugnant obsessions). The current study aimed to investigate fear of self‐perceptions using the FSQ in an OCD sample (n = 144) and related psychological disorders (eating disorders, n = 57; body dysmorphic disorder, n = 33) in comparison to a non‐clinical (n = 141) and clinical comparison group (anxiety/depressive disorders, n = 27). Following an exploratory factor analysis of the scale in the OCD sample, the results showed that participants with OCD in general did not score significantly higher on fear of self‐perceptions than did the clinical comparison participants. However, consistent with previous findings, fear of self was highly characteristic among OCD patients with unwanted repugnant thoughts and impulses. In addition, fear of self‐perceptions were significantly more elevated in those with eating or body dysmorphic disorders relative to the other non‐clinical and clinical groups. The construct of a “feared possible self” may be particularly relevant in disorders where negative self‐perception is a dominant theme, either involving concerns about one's inner self or concerns related to perceived bodily faults.     

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. © 2013 Wiley Periodicals, Inc.     

Genome‐wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder

Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations. Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #572 evaluated cognitive and functional capacity measures among SZ and BP patients. In conjunction with the VA Million Veteran Program, 3,959 European American (1,095 SZ, 2,864 BP) and 2,601 African American (1,095 SZ, 2,864 BP) patients were genotyped using a custom Affymetrix Axiom Biobank array. We performed a genome‐wide association study of global cognitive functioning, constructed polygenic scores for SZ and cognition in the general population, and examined genetic correlations with 2,626 UK Biobank traits. Although no single locus attained genome‐wide significance, observed allelic effects were strongly consistent with previous studies. We observed robust associations between global cognitive functioning and polygenic scores for cognitive performance, intelligence, and SZ risk. We also identified significant genetic correlations with several cognition‐related traits in UK Biobank. In a diverse cohort of U.S. veterans with SZ or BP, we demonstrate broad overlap of common genetic effects on cognition in the general population, and find that greater polygenic loading for SZ risk is associated with poorer cognitive performance.     

Additional evidence that genetic variation of MAO‐A gene supports a gender subtype in obsessive‐compulsive disorder

Studies have recently reported a sexually dimorphic association between obsessive‐compulsive disorder (OCD) and a polymorphism related with variations in MAO‐A activity. These observations suggest the possibility of gender differences in genetic susceptibility for OCD. We thus reexamined the MAO‐A/EcoRV polymorphism in a sample of 122 OCD patients and 124 healthy subjects. An excess of allele 1 in OCD females with major depression disorder was confirmed as previously reported. This difference was more strongly associated with OCD females than males in the total sample. Finally, we analyzed a sample of 51 OCD trios. Haplotype‐based haplotype relative risk (HHRR) analysis of the inheritance of the MAO‐A variants revealed in the female probands that 14 out of 19 transmitted the allele 1, providing significant evidence for an allelic association between OCD and MAO‐A gene. In conclusion, our findings may provide molecular evidence to identify a clinically meaningful gender subtype. However, an effort should be made to replicate the analysis in larger samples of informative parents using strategies such as transmission disequilibrium test to allow definite conclusions. © 2001 Wiley‐Liss, Inc.     

Volitional saccade performance in a large sample of patients with obsessive‐compulsive disorder and unaffected first‐degree relatives

Recent evidence indicates that patients with obsessive‐compulsive disorder (OCD) as well as their unaffected first‐degree relatives show deficits in the volitional control of saccades, suggesting that volitional saccade performance may constitute an endophenotype of OCD. Here, we aimed to replicate and extend these findings in a large, independent sample. One hundred and fifteen patients with OCD, 103 healthy comparison subjects without a family history of OCD, and 31 unaffected first‐degree relatives of OCD patients were examined using structured clinical interviews and performed a volitional saccade task as well as a prosaccade task. In contrast to previous reports, neither patients nor relatives showed impairments in the performance of volitional saccades compared to healthy controls. Notably, medicated patients did not differ from nonmedicated patients, and there was no effect of depressive comorbidity. Additional analyses investigating correlations between saccade performance and OCD symptom dimensions yielded no significant associations. In conclusion, the present results do not support the notion that volitional saccade execution constitutes an endophenotype of OCD. Possible explanations for inconsistencies with previous studies are discussed.     

Genome‐wide linkage analysis of families with obsessive‐compulsive disorder ascertained through pediatric probands

The goal of this study was to identify chromosomal regions likely to contain susceptibility alleles for early‐onset obsessive‐compulsive disorder (OCD). A genome scan was done in 56 individuals from seven families ascertained through pediatric OCD probands; 27 of the 56 subjects had a lifetime diagnosis of definite OCD. Denser mapping of regions on chromosomes 2, 9, and 16 was subsequently done with those subjects and ten additional subjects from the largest family in the study. Direct interviews were completed with 65 of the 66 genotyped individuals. Relatives were interviewed blind to proband status. Of the 65 interviewed individuals, 32 had a lifetime diagnosis of definite OCD. Three of the seven probands had a history of Tourette disorder. Two of the 25 relatives with OCD had a tic history, whereas none of the 33 relatives without OCD had tics. The genome scan consisted of 349 microsatellite markers with an average between‐marker distance of 11.3 centiMorgan (cM). Fine mapping was done with 24 additional markers at an average spacing of 1.6 cM. Parametric and nonparametric linkage analyses were conducted using GENEHUNTER⁺. The maximum multipoint LOD score with a dominant model was 2.25 on 9p. However, with fine mapping and additional subjects, that LOD score decreased to 1.97. The maximum multipoint nonparametric LOD* score was 1.73 on 19q. The maximum multipoint LOD score with a recessive model was 1.40 on 6p. The results provide suggestive evidence for linkage on 9p and identify regions requiring further study with much larger samples. © 2002 Wiley‐Liss, Inc.     

Genetic Factors in Nonsmokers with Age‐Related Macular Degeneration Revealed Through Genome‐Wide Gene‐Environment Interaction Analysis

Relatively little is known about the interaction between genes and environment in the complex etiology of age‐related macular degeneration (AMD). This study aimed to identify novel factors associated with AMD by analyzing gene‐smoking interactions in a genome‐wide association study of 1207 AMD cases and 686 controls of Caucasian background with genotype data on 668,238 single nucleotide polymorphisms (SNPs) after quality control. Participants’ history of smoking at least 100 cigarettes lifetime was determined by a self‐administered questionnaire. SNP associations modeled the effect of the minor allele additively on AMD using logistic regression, with adjustment for age, sex, and ever/never smoking. Joint effects of SNPs and smoking were examined comparing a null model containing only age, sex, and smoking against an extended model including genotypic and interaction terms. Genome‐wide significant main effects were detected at three known AMD loci: CFH (P = 7.51×10^?30), ARMS2 (P = 1.94×10^?23), and RDBP/CFB/C2 (P = 4.37×10^?10), while joint effects analysis revealed three genomic regions with P < 10^?5. Analyses stratified by smoking found genetic associations largely restricted to nonsmokers, with one notable exception: the chromosome 18q22.1 intergenic SNP rs17073641 (between SERPINB8 and CDH7), more strongly associated in nonsmokers (OR = 0.57, P = 2.73 × 10^?5), with an inverse association among smokers (OR = 1.42, P = 0.00228), suggesting that smoking modifies the effect of some genetic polymorphisms on AMD risk.     

A case–control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE)

Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p‐value = 6.24 × 10^?8), rs74477937 (p‐value = 8.56 × 10^?8) and rs78707086 (p‐value = 8.55 × 10^?8) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta‐analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.     

Genome‐wide association study of theta band event‐related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence

Event‐related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome‐wide association study (GWAS) of an ERO endophenotype—frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty‐two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family‐based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two‐stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10^?6). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10^?4), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM‐IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case–controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case–control and family‐based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders. © 2010 Wiley‐Liss, Inc.