A family study of early-onset obsessive-compulsive disorder

Abstract

Results from family studies have suggested that obsessive-compulsive disorder (OCD) is a genetically heterogeneous disorder and have emphasized the importance of identifying valid subgroups of patients. The current study focused on early-onset OCD probands and examined the recurrence risks of OCD and tics among first-degree family members. One hundred six children and adolescents with OCD were recruited from a specialty clinic for OCD and 44 control individuals without OCD were identified by random-digit dialing. These 150 probands and their 465 first-degree relatives were assessed by trained interviewers, using standardized semi-structured interviews. Diagnoses were assigned according to DSM-IV criteria by two experts blind to the proband's diagnosis, through the best-estimate process. These data were analyzed using chi(2) tests, t-tests, logistic regression, and generalized estimating equations (GEE). Case probands had a mean age of onset of OC symptoms of 6.7 years (SD = 2.8), and high comorbid rates with Tourette syndrome (33%) and chronic tics (13.2%). Compared to control relatives, case relatives had higher age-corrected recurrence risks of OCD (22.7% vs. 0.9%, odds ratio (OR) = 32.5, 95% confidence interval (CI) = 4.5-230.8, P = 0.0005), and chronic tics (11.6% vs. 1.7%, OR = 7.9, 95% CI = 1.9-33.1, P = 0.005). A comorbid diagnosis of tics in the relatives was the best predictor of their diagnosis of OCD (OR = 7.35, 95% CI = 3.79-14.25, P < 0.0001). There was a significant correlation between the ages of onset of OCD in probands and their affected relatives. Childhood onset OCD is a highly familial disorder. Some early-onset cases may represent a valid subgroup, with higher genetic loading and shared vulnerability with chronic tic disorders.

Population-Based, Multigenerational Family Clustering Study of Obsessive-compulsive Disorder

“…Similar studies 7,8 conducted in juvenile cases of OCD reported even higher familial risks. A recent meta-analysis 9 of 6 adult and 5 pediatric OCD family studies reported odds ratios (ORs) for OCD of 4.7 (99% CI, 2.4-9.2) and 25.6 (99% CI, 9.3-70.6), respectively.…”

Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study

“…Probands were included if OCD symptom onset occurred before age 18 [early onset appeared associated with familiality in some studies [e.g., Pauls et al, 1995;Nestadt et al, 2000b;do Rosario-Campos et al, 2005] but not all [Fyer et al, 2005;Grabe et al, 2006]]. Probands with schizophrenia, severe mental retardation, Tourette's disorder, or OCD which occurred exclusively in the context of depression (''secondary OCD'') were excluded.…”

“…OCD itself is a familial [Pauls et al, 1995;Nestadt et al, 2000b;Fyer et al, 2005;do Rosario-Campos et al, 2005;Hanna et al, 2005b;Grabe et al, 2006] and heritable condition [Inouye, 1965;Carey and Gottesman, 1981;Nestadt et al, 2000a;Hudziak et al, 2004;van Grootheest et al, 2005]. However, molecular genetic studies of OCD are in their relative infancy, as are molecular genetic studies of GDs.…”

Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

“…114 Although the etiology of OCD remains unknown, the results of twin studies, familial studies, and segregation analysis have provided evidence that OCD has a strong genetic component. [115][116][117][118][119] Some investigators have also found markers of oxidative stress in the brain tissues of patients with OCD. [120][121][122] Moreover, Kuloglu et al 120 showed significantly lower levels of vitamin E and C, and higher levels of malondialdehyde (MDA) in patients with OCD compared to controls, suggesting that OCD is linked to oxidative stress.…”