Latent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of symptoms; but person-centered latent methods have seen little use. This study was designed to uncover sets of homogeneous groupings within 1611 individuals with OCD based on symptoms. METHOD: Latent class analysis models using 61 obsessive-compulsive symptoms collected from the Yale-Brown Obsessive-Compulsive Scale were fit. Relationships between latent class membership and treatment response, sex, symptom severity, and comorbid tic disorders were tested for relationship to class membership. RESULTS: Latent class analysis models of best fit yielded 3 classes. Classes differed only in frequency of symptom endorsement. Classes with higher symptom endorsement were associated with earlier age of onset, being male, higher Yale-Brown Obsessive-Compulsive Scale symptom severity scores, and comorbid tic disorders. There were no differences in treatment response between classes. CONCLUSIONS: These results provide support for the validity of a single underlying latent OCD construct, in addition to the distinct symptom factors identified previously via factor analyses.

Symptom dimensions in OCD: item-level factor analysis and heritability estimates.

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.

The role of the COMT Val(158)Met polymorphism in the phenotypic expression of obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is characterized by the presence of obsessions and compulsions, and shows considerable phenotypic variability. Family and twin studies have indicated a genetic component in the etiology of OCD, and the catechol-O-methyl transferase (COMT) gene is an important candidate gene for OCD. This study investigates the influence of the functional COMT Val158Met polymorphism on the phenotypic expression of OCD, using an item-level factor-analytic approach in a large sample. The COMT Val158Met variant was genotyped in 373 patients and 462 controls. It was tested whether there was an association between the COMT Val158Met polymorphism and OCD or dimensional phenotypes such as YBOCS severity score, age of onset of obsessive-compulsive symptoms and six symptom dimensions recently found in a large item-level factor-analytic study [Katerberg et al., submitted]. We further investigated possible sex-specific associations between the COMT Val158Met polymorphism and OCD or dimensional phenotypes. There was a trend for an association of the COMT 158Met allele with OCD in males, and an interaction between the COMT Val158Met genotype and sex on the somatic and sensory phenomena symptom dimension, with females showing lower scores. In conclusion, a dimensional approach seems fruitful in detecting genes of importance for OCD.

The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive-compulsive disorder (OCD).

Evidence suggests that the Val66Met variant of the brain-derived neurotrophic factor (BDNF) gene may play a role in the etiology of Obsessive-Compulsive Disorder (OCD). In this study, the role of the BDNF Val66Met variant in the etiology and the phenotypic expression of OCD is investigated. Associations between the BDNF Val66Met variant and OCD, obsessive-compulsive symptom dimensions, Yale-Brown Obsessive Compulsive Scale (YBOCS) severity scores, age of onset and family history of obsessive-compulsive symptoms were assessed. The BDNF Val66Met variant was genotyped in 419 patients with sub-/clinical OCD and 650 controls. No differences in allele or genotype frequency were observed between cases and controls. In females with OCD, the Met66Met genotype was associated with later age of onset and a trend for a negative family history, whereas the Val66Val genotype was associated with a trend for lower YBOCS severity scores. Item-level factor analysis revealed six factors: 1) Contamination/cleaning; 2) Aggressive obsessions/checking; 3) Symmetry obsessions, counting, ordering and repeating; 4) Sexual/religious obsessions; 5) Hoarding and 6) Somatic obsessions/checking. A trend was found for a positive association between Factor 4 (Sexual/religious obsessions) and the BDNF Val66Val genotype. The results suggest that BDNF function may be implicated in the mediation of OCD. We found that for the BDNF Met66Met genotype may be associated with a milder phenotype in females and a possible role for the BDNF Val66Val genotype and the BDNF Val66 allele in the sexual/religious obsessions.

High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics.

BACKGROUND: Among the most frequently encountered mutations in dilated cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to analyze the LMNA gene in patients with DCM and/or conduction disease referred to the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA mutations and their clinical expression. METHODS AND RESULTS: The LMNA gene was screened in 61 index patients. Eleven mutations (including 6 novel) were identified, mainly in the subgroup of familial DCM with cardiac conduction disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb-Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In addition, a mutation was identified in 1 of 4 families with only cardiac conduction disease. We did not identify any large deletions or duplications. Genotype-phenotype relationships revealed a high rate of sudden death and cardiac transplants in carriers of the p.N195K mutation. Our study confirmed that the p.R225X mutation leads to cardiac conduction disease with late or no development of DCM, underscoring the importance of this mutation in putative familial "lone conduction disease." Nearly one third of LMNA mutation carriers had experienced a thromboembolic event. CONCLUSIONS: This study highlights the role of LMNA mutations in DCM and related disorders. A severe phenotype in p.N195K mutation carriers and preferential cardiac conduction disease in p.R225X carriers was encountered. Because of the clinical variability, including the development of associated symptoms in time, LMNA screening should be considered in patients with DCM or familial lone conduction disease.