Familiality of Factor Analysis-Derived YBOCS Dimensions in OCD-Affected Sibling Pairs from the OCD Collaborative Genetics Study

Hasler, Gregor; Pinto, Anthony; Greenberg, Benjamin D.; Samuels, Jack; Fyer, Abby J.; Pauls, David L.; Knowles, James A.; McCracken, James T.; Piacentini, John; Riddle, Mark A.; Rauch, Scott L.; Rasmussen, Steven A.; Willour, Virginia L.; Grados, Marco A.; Cullen, Bernadette; Bienvenu, O. Joseph; Shugart, Yin Yao; Liang, Kung‐Yee; Hoehn‐Saric, Rudolf; Wang, Ying; Ronquillo, Jonne G.; Nestadt, Gerald; Murphy, Dennis L.

doi:10.1016/j.biopsych.2006.05.040

Cited by 151 publications

(140 citation statements)

References 47 publications

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“…These results support the findings of some of the family studies investigating the familiality of OC symptom dimensions, based on Y-BOCS items [Leckman et al, 2003;Hasler et al, 2007]. Hasler et al [2007] found significant sib-sib correlations for Checking compulsions and the Contamination/ Cleaning dimension.…”

Section: Discussionsupporting

confidence: 89%

“…These two Y-BOCS dimensions are comparable with the PI-R Checking and Contamination dimensions we found. However, we found no familial effects for the Checking dimension, but the study of Hasler et al [2007] did not account for the possibility of common versus specific familial effects.…”

Section: Discussioncontrasting

confidence: 80%

“…Hasler et al [2007] found significant sib-sib correlations for Checking compulsions and the Contamination/ Cleaning dimension. These two Y-BOCS dimensions are comparable with the PI-R Checking and Contamination dimensions we found.…”

Section: Discussionmentioning

confidence: 88%

“…Significant correlations were observed between sib pairs as well as mother-child pairs for the ''aggressive/sexual/religious obsessions and checking compulsions'' factor, and for the ''symmetry/ordering obsessions and compulsions'' factor. Recently, Hasler et al [2007] evaluated the familiality of different Y-BOCS dimensions within 418 sib pairs. Robust sib-sib intraclass correlations of around 0.2 were found for two of the four Y-BOCS factors: ''hoarding obsessions and compulsions'', and ''aggressive/ sexual/religious obsessions and checking compulsions''.…”

Section: Introductionmentioning

confidence: 99%

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Heritability of obsessive‐compulsive symptom dimensions

Grootheest

Boomsma

Hettema

et al. 2008

American J of Med Genetics Pt B

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Recent research has shown that obsessivecompulsive symptoms (OCS) differ remarkably among patients and can be divided into several symptom dimensions. OCS are influenced by genetic components, but it is unknown to what extent these symptom dimensions are heritable. The phenotypic heterogeneity also raises the question to what extent the symptom dimensions are influenced by specific or shared genetic factors. We studied a population sample of 1,383 female twins from the Virginia Twin Registry. OCS was measured by a questionnaire with 20 items from the Padua Inventory. After factor analysis, three reliable OC symptom dimensions were retained: Rumination, Contamination, and Checking. These OC dimensions were analyzed with multivariate genetic models to investigate both the overlap and uniqueness of genetic and environmental contributions underlying OC symptom dimensions. The multivariate common pathway model provided the best description of the data. All symptom dimensions share variation with a latent common factor, that is, OC behavior. Variation in this common factor was explained by both genes (36%) and environmental factors (64%). Only the Contamination dimension was influenced by specific genes and seemed to be a relatively independent dimension. The results suggest that a broad OC behavioral phenotype exists, influenced by both genes and nonshared environment. In addition, we found evidence for specific genetic and environmental factors underlying the Contamination dimension. Use of the Contamination dimension could therefore provide a powerful approach for the detection of genetic susceptibility loci that contribute to OCS.

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Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Heritability of obsessive‐compulsive symptom dimensions

Grootheest

Boomsma

Hettema

et al. 2008

American J of Med Genetics Pt B

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“…It remains to be determined whether the clinical differences identified in this study reflect sex-specific differences in the course and expression of an underlying hoarding vulnerability, or in etiology and pathogenesis. Interestingly, the sib-sib correlation of hoarding dimension scores has been found to be stronger for hoarding than for other OCD symptom dimensions, and stronger in female-female than male-male sibling pairs, in the OCGS (Hasler et al, 2007) and other studies (Chacon et al, 2007). Moreover, there is evidence for linkage of OCD to several chromosomal regions, including the X chromosome, in families with multiple hoarding relatives (Samuels et al, 2007b).…”

Section: Discussionmentioning

confidence: 99%

Sex-specific clinical correlates of hoarding in obsessive-compulsive disorder

Samuels

Bienvenu

Pinto

et al. 2008

Behaviour Research and Therapy

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Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions. In men, hoarding was associated with generalized anxiety disorder and tics whereas, among women, hoarding was associated with social phobia, post-traumatic stress disorder, body dysmorphic disorder, nail biting, and skin picking. In women but not men, hoarding was associated with schizotypal and dependent personality disorder dimensions, and with low conscientiousness. These findings indicate that specific clinical correlates of hoarding in OCD are different in men and women and may reflect sex-specific differences in the course, expression, and/or etiology of hoarding behavior in OCD. KeywordsObsessive-compulsive disorder; hoarding; comorbidity; personality disorders; personality; sex differences *Corresponding author: Jack Samuels, Ph.D., Department of Psychiatry and Behavioral Sciences, Johns Hopkins, University School of Medicine, 600 N. Wolfe Street, Meyer 4-181, Baltimore, MD 21287-7228. Phone: 410-614-4942; Fax: 410-614-8137, E-mail address: jacks@jhmi.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptHoarding behavior has been called "pathological collecting" and is characterized by the acquisition of, and unwillingness or inability to discard, large quantities of seemingly useless objects (Greenberg, Witztum & Levy, 1990;Frost & Gross, 1993). The behavior can lead to significantly cluttered living space in the home and can cause considerable distress and impairment in functioning for individuals and their family members (Tolin et al., 2008). The clutter may interfere with the normal use of space for basic household activities and increase the risk of injuries due to fire and falling, and illnesses due to poor sanitation, as well as legal citations and evictions from home by public health authorities . Although hoarding behavior can occur in several psychiatric conditions, including dementia, mental retardation, schizophrenia, and eating disorders (Damecour & Charron, 1998), it appears to occur most frequently in the context of obsessive-compulsive disorder (OCD), presenting in 20-30% or more of patients with this condition (Rasmussen & Eisen, 1992; Frost, Krause, & Steketee, 1996).Over the past decade, considerable evidence has accumulated that OCD-affected individuals with hoarding behavior show clinical differences from those without hoarding behavior. These differences include greater severity of OCD, as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) (Goo...

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A Haplotype Containing Quantitative Trait Loci for SLC1A1 Gene Expression and Its Association With Obsessive-Compulsive Disorder

Wendland

Moya

Timpano³

et al. 2009

Arch Gen Psychiatry

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119

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Context Recent evidence from linkage analyses and follow-up candidate gene studies supports the involvement of SLC1A1, which encodes the neuronal glutamate transporter, in the development of obsessive-compulsive disorder (OCD). Objectives To determine the role of genetic variation of SLC1A1 in OCD in a large case-control study and to better understand how SLC1A1 variation affects functionality. Design A case-control study. Setting Publicly accessible SLC1A1 expression and genotype data. Patients Three hundred twenty-five OCD probands and 662 ethnically and sex-matched controls. Interventions Probands were assessed with the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive Compulsive Scale, and the Saving Inventory–Revised. Six single-nucleotide polymorphisms (SNPs) were genotyped. Multiple testing corrections for single-marker and haplotype analyses were performed by permutation. Results Gene expression of SLC1A1 is heritable in lymphoblastoid cell lines. We identified 3 SNPs in or near SLC1A1 that correlated with gene expression levels, 1 of which had previously been associated with OCD. Two of these SNPs also predicted expression levels in human brain tissue, and 1 SNP was further functional in reporter gene studies. Two haplotypes at 3 SNPs, rs3087879, rs301430, and rs7858819, were significantly associated with OCD after multiple-testing correction and contained 2 SNPs associated with expression levels. In addition, another SNP correlating with SLC1A1 gene expression, rs3933331, was associated with an OCD-hoarding subphenotype as assessed by 2 independent, validated scales. Conclusions Our case-control data corroborate previous smaller family-based studies that indicated that SLC1A1 is a susceptibility locus for OCD. The expression and genotype database–mining approach we used provides a potentially useful complementary approach to strengthen future candidate gene studies in neuropsychiatric and other disorders.

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Familiality of Factor Analysis-Derived YBOCS Dimensions in OCD-Affected Sibling Pairs from the OCD Collaborative Genetics Study

Cited by 151 publications

References 47 publications

Heritability of obsessive‐compulsive symptom dimensions

Heritability of obsessive‐compulsive symptom dimensions

Sex-specific clinical correlates of hoarding in obsessive-compulsive disorder

A Haplotype Containing Quantitative Trait Loci for SLC1A1 Gene Expression and Its Association With Obsessive-Compulsive Disorder

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