This is the largest item-level factor-analytic and heritability study conducted to date for OC symptoms. The sample size of 1224 affected subjects provides analytic power previously unavailable for OCD symptom dimension research. Results support the assertion that both OCD and its symptom dimensions are heritable and, thus, are of value for use in future genetics research. They also raise the possibility that the genes and gene networks underlying common susceptibility to OCD differ from those underlying distinct symptom dimensions. Consistent with previous smaller item-level factor-analytic studies, five symptom factors have been identified, i.e.: (1) taboo (religious, sexual, and aggressive obsessions) symptoms, (2) contamination and cleaning symptoms, (3) doubts (fears of harming self or others, doubting and checking symptoms), (4) superstitions and rituals, and (5) hoarding and symmetry symptoms (including perfectionism). This symptom dimension model reveals substantial overlap with the factor structures identified in previous item-level analyses, (Denys et al. 2004
; Feinstein et al. 2003
; Girishchandra and Khanna 2001
; Hantouche and Lancrenon 1996
; Pinto et al. 2008
; Stein et al. 2007
; Wu et al. 2007
), with two key differences. First, somatic items did not load consistently on any of the factors, and second, the rituals/superstition factor is new, containing predominantly miscellaneous items excluded from most previous studies.
The first distinction between this and other item-level factor analyses that somatic items on the YBOCS-CL did not load consistently on any factors, is consistent with a recent study by Cullen et al. (2007
). In the present sample, better fit and more stable solutions were obtained when somatic items were omitted from analyses. This finding suggests that some somatic items, although often clinically co-occurring with OCD, do not represent core OC symptoms and may contribute to observed phenotypic and genotypic OCD heterogeneity. Instead, the somatic items may be related to hypochondriasis, a frequently comorbid illness with OCD (Bienvenu et al. 2000
). Recent phenomenological and neuroimaging studies have shown a clear distinction between hypochondriasis and OCD, despite some shared phenotypic and brain function characteristics (Greeven et al. 2006
; van den Heuvel et al. 2005
The second notable distinction between this and previous item-level factor analyses is the emergence of a rituals/superstition factor. This is mainly comprised of items from the miscellaneous YBOCS-CL sections, which were excluded from past studies. However, it is unclear whether this new factor reflects either a subdomain of the OCD phenotype or a co-occurring symptom dimension that is more distally etiologically related to OCD. Although heritability was demonstrated for this dimension, and may potentially be of use for clinical outcome research, one might consider omitting this factor from future studies. Indeed, the inability to perform reliable bivariate genetic analyses using this factor, coupled with the difficulty of interpreting its symptom constituents illustrates a weakness of the YBOCS-CL, i.e. that over the years items have been added to the scale without investigating whether the items are in fact OCD-related, carrying the risk of introducing phenotypic bias.
This study provides evidence that OCD diagnosis may be dissected into non-mutually exclusive, consistent and homogeneous symptom dimensions, given the stability of symptoms within factors across models, the high internal consistency of the factors, and the high heritability estimates of the factors. Of note, the category-based factor analysis conducted on this sample yielded similar results to those previously reported in other samples (rather than being similar to the item-level analysis on this sample). Direct comparison of the item-level and category-based FAs in this study showed similarities only for the factors contamination/washing, and for the taboo factor of the item-level analysis and the obsession factor of the category-based FA.
Previous heritability studies that used category-based analyses predominantly used sib-sib correlations and yielded mixed results, especially with respect to heritability estimates of the symmetry/ordering factor (Chacon et al. 2007
; Cullen et al. 2007
; Hasler et al. 2007
). This study, in which the symmetry factor obtained using the category-based approach was not heritable, corroborates these inconsistent findings. Interestingly, consistent with the first categorical factor analyses in OCD (Baer 1994
), the item-level approach resulted in hoarding/symmetry behaviors constituting a heritable factor in this study. Moreover, this factor showed the highest genetic correlation with a latent or underlying OC susceptibility (as measured by YBOCS severity). This may be an artifact of the available family data, which contained a substantial number of hoarding families, or it may alternatively reflect a genuine relationship between these constructs. This finding, along with the other heritability results, requires replication in an independent sample. Further, the contamination/wash factor showed a significant genetic correlation with underlying OC susceptibility. Interestingly, the contamination and hoarding/symmetry factor showed significant genetic correlations as well, as did the taboo and doubts factor. This latter correlation corroborates previous work in college students and clinical samples strongly suggesting a heritable obsessionality factor strongly related to OCD (Mathews et al. 2008
Notably, although not providing the best statistical fit for the data, a one-factor model also emerged as a possible solution according to the eigen structure, as evidenced by the scree plot. The heritability analyses suggested that a one-factor solution was at least as heritable as the majority of the individual factors, and that although it shared genetic influences with YBOCS total severity, there were also independent genetic influences for this construct. Thus, although we did not directly test this, the results suggest that, in addition to individual genetic influences determining specific symptom expression, there may be a heritable underlying susceptibility to OC symptoms in general. These findings are in line with (1) a recent population-based twin study of OC symptom dimensions; (2) a family study of OC symptoms in extended families, both of which found evidence of one heritable underlying latent susceptibility to OC symptoms along with specific genetic contributions to OC symptom dimensions (van Grootheest et al. 2008
; Mathews et al. 2008
); and (3) with a parallel study on the same data set as used in this study, using latent class analyses, which showed that a three class solution provided the best fit, the classes only differing on level of symptom endorsement. These converging data suggest that OCD as a single entity is a valid model to attain to (De Lucchi et al. in review).
The negative associations between factor scores and age of onset are in concordance with previous research reporting a higher number of obsessions and compulsions and higher symptom severity in subjects with early onset compared to subjects with late onset OCD (Millet et al. 2004
). Higher mean scores on the “taboo” factor (aggressive and sexual obsessions) in men than in women is consistent with other reports as well (Torresan et al. 2009
). This predominance of aggressive and sexual obsessions among men with OCD holds across cultures (Jaisoorya et al. 2009
). Finally, overrepresentation of the “rituals and superstition” factor in men in this study has also been reported previously (Jaisoorya et al. 2009
), adding to reported gender differences with respect to phenotypic expression of OCD.
The main methodological strengths of this study include: (1) the large sample size; (2) the use of improved statistical methodology over some previous studies; (3) heritability analyses in large multigenerational families with multiple OCD-affected individuals, thus improving the precision of heritability estimates, and (4) generalizability of findings.
The heterogeneity of the sample and the potentially differential application and interpretation of the YBOCS-SC individual items across sites are the principal limitations of this study. No inter-rater reliability data were available across sites on the YBOCS-SC and therefore, substantial variability due to measurement error cannot be ruled out. Moreover, some sites measured current endorsement whereas others measured lifetime endorsement. Paradoxically, the sample heterogeneity may also be viewed as a principal strength. Although such heterogeneity may theoretically contribute to the instability of resulting models, the ultimate best-fit model was remarkably stable and most likely a result of the large sample size. The sample heterogeneity also increases generalizability of the findings to other OCD samples. Although the individual items within YBOCS-CL categories are not operationally defined, and their psychometric properties seem to be weaker than some other measures used in OCD research contexts, the YBOCS is arguably the most extensively used clinical assessment of obsessive-compulsive symptoms worldwide, and is easily completed both by OCD-affected individuals and clinicians. Use of this instrument in these analyses adds to the interpretability and accessibility of the results by clinicians using the YBOCS in their practice, and facilitates replication efforts on additional samples. An additional perceived study limitation may be the number of families available for the heritability analyses, which was relatively small compared to appropriately powered twin studies. However, the number and pedigree structures of the families included here have sufficient a priori
power to detect heritability estimates of 30% or higher, according to Schork and Schork (1993
). An advantage of this approach over a twin-family approach is that relatively small numbers of families are required, increasing the feasibility for a replication in subsequent studies.
In summary, in the face of an emerging need to refine the OCD phenotype for genetic, clinical and translational studies, these results provide evidence for ongoing utility of both the OCD DSM phenotype as a whole and of specific OC symptom dimension subgroups. An item-level derived five factor model accounts for a similar proportion of explained symptom variance as category-derived models. Moreover, supporting recently emergent twin and family study findings, heritability calculations suggest the presence of both common and distinct biologic underpinnings of OCD and its symptom dimensions. They bolster the current hypothesis that OCD is genetically complex, with multiple genetic and environmental factors contributing to its development.