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Objective: Individuals with obsessive-compulsive disorder (OCD) who have compulsive hoarding behavior are clinically different from other OCD-affected individuals. The objective of this study was to determine whether there are chromosomal regions specifically linked to compulsive hoarding behavior in families with obsessive-compulsive disorder. Methods: The authors used multipoint allele-sharing methods to assess for linkage in 219 multiplex OCD families collected as part of the OCD Collaborative Genetics Study. The authors treated compulsive hoarding as the phenotype of interest and also stratified families into those with and without two or more relatives affected with compulsive hoarding. Results: Using compulsive hoarding as the phenotype, there was suggestive linkage to chromosome 14 at marker D14S588 (Kong and Cox logarithm of the odds ratio [LOD] [KA[C.sub.all]=2.9]). In families with two or more hoarding relatives, there was significant linkage of OCD to chromosome 14 at marker C14S1937 (KA[C.sub.all]=3.7), whereas in families with fewer than two hoarding relatives, there was suggestive linkage to chromosome 3 at marker D3S2398 (KA[C.sub.all]=2.9). Conclusions: The findings suggest that a region on chromosome 14 is linked with compulsive hoarding behavior in families with OCD.

Objective: The purpose of the study was to examine adaptive, emotional, and family functioning in a well-characterized group of children and adolescents with obsessive-compulsive disorder (OCD) and to evaluate the influence of comorbid attention deficit hyperactivity disorder (ADHD) on the levels of impairment in various functional domains. Method: The study group included 287 children and adolescents (191 boys, 96 girls) ages 7-18 years. Fifty-six subjects had a diagnosis of OCD only, 43 had both OCD and ADHD, 95 had ADHD, and 93 were unaffected comparison children. Best estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. The children's functioning was evaluated with a comprehensive battery of well-established, standardized measures, including the Vineland Adaptive Behavior Scales, parents' ratings of social and family functioning, and children's self-reports of emotional adjustment. Results: The children with OCD only were more impaired than were unaffected comparison subjects in most areas of adaptive functioning and emotional adjustment. Children with OCD plus ADHD had additional difficulties in social functioning, school problems, and self-reported depression. Impairment in daily living skills, reduced number of activities, and self-reported anxiety were uniquely associated with the diagnosis of OCD. Family dysfunction was associated with ADHD but not with OCD. Conclusions: Children and adolescents with OCD are impaired in multiple domains of adaptive and emotional functioning. When comorbid ADHD is present, there is an additional burden on social, school, and family functioning.

Objective: Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands. Method: The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives. Results: Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands. Conclusions: Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies.

Objective: Gilles de la Tourette's syndrome is a well-characterized disorder with clear DSM-IV criteria. However, the great deal of clinical variability across patients may represent an underlying etiologic complexity. Issues of phenotypic heterogeneity are particularly critical to current efforts at mapping genes involved in this syndrome. Method: Lifetime tic symptom data were obtained from direct structured interviews of 85 Tourette's disorder probands. Information on 29 tic symptoms was elicited. The probands' tic symptoms were grouped by using agglomerative hierarchical clustering, with no a priori assumptions concerning the relatedness of symptoms. Scores for the probands' symptom clusters were used as variables in a principal-component factor analysis. The relationships of the resulting factor scores to comorbidity in probands and recurrence risks in relatives were examined. In addition, intraclass correlations were calculated for within-family factor scores of 36 families. Results: Four significant factors were identified: 1) aggressive phenomena (e.g., kicking, temper fits, argumentativeness), 2) purely motor and phonic tic symptoms, 3) compulsive phenomena (e.g., touching of others or objects, repetitive speech, throat clearing), and 4) tapping and absence of grunting. Analysis of the symptom loadings, comorbidity, recurrence risks, and within-family correlations indicate that these factors represent a valid structure with clinical and biological relevance. Conclusions: In this symptom-based factor analysis of Tourette's disorder, four factors accounted for 61% of the phenotypic symptom variance in Tourette's disorder probands and their first-degree relatives. Three of these factors may indicate the presence of heritable components of the Tourette's disorder phenotype. (Am J Psychiatry 2002; 159:291-296)

Objective: Tourette's syndrome is a chronic disorder of childhood onset that is characterized by motor and phonic tics and a broad range of associated behavior including obsessive-compulsive symptoms. Less well appreciated are the sensory and other perceptually tinged mental phenomena associated with both tic and compulsive behavior. This cross-sectional study evaluated the 'just-right' phenomena commonly associated with compulsive behavior in subjects with tic disorders. Method: A total of 134 subjects with tic disorders, aged 9 to 71 years, completed a questionnaire concerning their current and past tic symptoms. Subjects were also asked to describe their 'just right' perceptions. The Yale-Brown Obsessive Compulsive Scale was used to assess severity of current obsessive-compulsive symptoms. Results: Eighty-one percent of the subjects with both Tourette's syndrome and obsessive-compulsive disorder (N=31) and 56% of the subjects with Tourette's syndrome and obsessive-compulsive symptoms (N=61) reported being aware of a need to perform compulsions until they were 'just right.' This awareness most commonly referred to visual or tactile (as opposed to auditory) features of the compulsive act or its consequences. Three-quarters of the subjects with these perceptions reported that they usually were aware of them immediately before or concurrently with the initiation of compulsions. Conclusions: While epidemiological studies of tic disorders and obsessive-compulsive disorder have yet to incorporate questions concerning 'just right' perceptions, these results suggest that such perceptions may be commonplace in adolescent and adult subjects with both obsessive-compulsive disorder and tic disorders. They also implicate brain regions involved in the processing of sensorimotor information in the pathobiology of tic disorders.

Objective: The authors' goal was to establish if a mutation in D(sub 1) dopamine receptor locus (DRD1), or one genetically close to it, could cause Gilles de la Tourette's syndrome. Method: DRD1 and linked markers (D5S36, D5S61, and D5S62) were studied in a large Mennonite Tourette's syndrome kindred. Only individuals with the full Tourette's syndrome were considered to be affected in one series of analyses; in another series the diagnostic spectrum was broadened to include chronic multiple tics. Liability classes were defined to take into account age at onset and sex differences; dominant inheritance was assumed. The authors' version of the LINKMAP program of the LINKAGE package modified to run under distributed parallel processing (Linda LINKMAP) was used for the multipoint linkage analysis. Results: Complete (theta=0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly. The area of exclusion of linkage (lod score between -2 and -10.5) extended from map position -0.10 to map position 0.50. The authors conducted an additional (centromeric) multipoint analysis with D5S36 as well as glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area of exclusion to map position -0.30 when the disease was defined narrowly. Conclusions: This result provides strong evidence against linkage of the DRD1 D(sub 1) dopamine receptor locus with Tourette's syndrome. This exclusion extends the authors' earlier work with the dopamine system in Tourette's syndrome to exclude the two best characterized dopamine receptors from linkage with Tourette's syndrome.