Admixture analysis of age at onset in obsessive–compulsive disorder

Delorme, Richard; Golmard, Jean‐Louis; Chabane, Nadia; Millet, Bruno; Krebs, Marie‐Odile; Mouren-Siméoni, M. C.; Leboyer, Marion

doi:10.1017/s0033291704003253

Cited by 110 publications

(91 citation statements)

References 30 publications

(35 reference statements)

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“…Our data indicate that the majority of patients experience significant symptoms before age 21, with only minor gender differences (figure 1). Of note, these data and those of others indicate a unimodal, non-normal distribution of age of OCD-related impairment [16], unlike some prior suggestions that age of OCD onset might have a bimodal pattern, with separate peaks in childhood and in adulthood [17].…”

Section: Obsessive-compulsive Disorder: a Brief Overview Of Phenomenocontrasting

confidence: 81%

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

Murphy

Moya

Fox

et al. 2013

Phil. Trans. R. Soc. B

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Individuals with obsessive–compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene ( SLC6A4 ), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders.

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Section: Obsessive-compulsive Disorder: a Brief Overview Of Phenomenocontrasting

confidence: 81%

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

Murphy

Moya

Fox

et al. 2013

Phil. Trans. R. Soc. B

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“…33 A closer look at the heritability estimates over time reveals that OCS is remarkably stable, with heritability estimates of approximately 55% at younger ages, 11 with a decrease at age 12, in which part of the variance was accounted for by shared environmental influences, continuing to 55% at ages 14 and 16, and 45% in adulthood. 15 This decrease in heritability between children/adolescents and adults may reflect the bimodal distribution found in the clinical OCD literature, 1,2 which found early-onset OCD to be associated with a higher genetic load compared to late-onset OCD.…”

Section: Discussionmentioning

confidence: 93%

“…In OCD, a bimodal distribution of age at onset has been found, with one peak occurring in preadolescent childhood and another peak in adulthood. 1,2 Early age at onset of OCD is also associated with tic disorder, 3,4 and the morbidity risk of OCD in family members of OCD subjects with early-onset OCD is higher than in relatives of late-onset OCD probands. 5,6 Furthermore, adult studies found an equal representation of men and women with OCD, or a slight female preponderance, whereas in clinical studies, early age at onset of OCD is associated with male preponderance.…”

mentioning

confidence: 99%

Genetic and Environmental Contributions to Self-Report Obsessive-Compulsive Symptoms in Dutch Adolescents at Ages 12, 14, and 16

Grootheest

Bartels

Beijsterveldt

et al. 2008

Journal of the American Academy of Child & Adolescent Psych

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“…Previous studies suggest that age of onset in OCD has two distributions [Delorme et al, 2005]. Moreover, early onset OCD has been found to represent a more familial phenotype of the disorder [Lenane et al, 1990;Pauls et al, 1995;Delorme et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

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

Katerberg

Löchner

Cath

et al. 2009

American J of Med Genetics Pt B

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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.

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Admixture analysis of age at onset in obsessive–compulsive disorder

Abstract: These results, based on a statistically validated AAO cut-off and those of previous studies on AAO in OCD, suggest that AAO is a crucial phenotypic characteristic in understanding the genetic basis of this disorder.

Cited by 110 publications

References 30 publications

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive–compulsive disorder as an example of overlapping clinical and genetic heterogeneity

Genetic and Environmental Contributions to Self-Report Obsessive-Compulsive Symptoms in Dutch Adolescents at Ages 12, 14, and 16

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

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