Early-onset Obsessive-compulsive Disorder Research Articles

Neuropsychological profiles of patients with obsessive-compulsive disorder: early onset versus late onset

In this study, we assess the neuropsychological profiles of both early and late symptom-onset obsessive-compulsive disorder (OCD) patients. The early and late-onset OCD patients are compared to the control group with a series of neuropsychological measurements. The late-onset OCD patients exhibited impaired performance on the immediate and the delayed recall conditions of the Rey-Osterrieth Complex Figure Test (RCFT) and the letter and category fluency of the Controlled Oral Word Association Test (COWA), compared to the normal controls and the early-onset OCD patients. The controls and early-onset OCD patients did not differ on any of the neuropsychological measurements taken in this study. These results suggest that different neurophysiological mechanisms are in play in early and late-onset OCD patients, and age of onset can serve as a potential marker for the subtyping of OCD.

Identification of pyruvate kinase as an antigen associated with Tourette syndrome

Immune responses to β-hemolytic streptococcal infections are hypothesized to trigger tic disorders and early-onset obsessive–compulsive disorder (OCD) in some pediatric populations. Here we identify the M1 isoform of the glycolytic enzyme, pyruvate kinase (PK) as an autoimmune target in Tourette syndrome and associated disorders. Antibodies to PK reacted strongly with surface antigens of infectious strains of streptococcus, and antibodies to streptococcal M proteins reacted with PK. Moreover, immunoreactivity to PK in patients with exacerbated symptoms who had recently acquired a streptococcal infection was 7-fold higher compared to patients with exacerbated symptoms and no evidence of a streptococcal infection. These data suggest that PK can function as an autoimmune target and that this immunoreactivity may be associated with Tourette syndrome, OCD, and associated disorders.

Association Testing of the Positional and Functional Candidate Gene SLC1A1/EAAC1 in Early-Onset Obsessive-compulsive Disorder

The first 2 independent linkage studies for obsessive-compulsive disorder (OCD) identified a region on 9p24 with suggestive evidence for linkage. The glutamate transporter gene solute carrier family 1, member 1 (SLC1A1) is a promising functional candidate in this region because altered glutamatergic concentrations have been found in the striatum and anterior cingulate in neuroimaging studies of pediatric OCD. To determine whether genotypes at polymorphisms in the SLC1A1 gene region are associated with early-onset OCD. Family-based analysis of association using the transmission disequilibrium test, confirmed using the family-based association test. Anxiety disorders program in an academic medical center. Seventy-one probands with DSM-III-R or DSM-IV OCD and their parents. Nine single nucleotide polymorphisms spaced throughout the SLC1A1 gene region were genotyped. Significant association was detected at rs3780412 (P = .04) and rs301430 (P = .03), 2 common adjacent single nucleotide polymorphisms in the 3' region of SLC1A1. Analysis by sex revealed that association at rs3780412 was limited to male probands (P = .002). Significant association was also detected for the T/C haplotype at rs301430-rs301979 (P = .03), the only haplotype block identified among the 9 single nucleotide polymorphisms. Analysis by sex also revealed that the haplotype association was limited to male probands (P = .003). A deletion in the 3' flanking region of SLC1A1 was also detected that imperfectly segregated with OCD in a large, multigenerational family with multiple affected individuals. The 3' region of SLC1A1 may contain a susceptibility allele for early-onset OCD, with differential effects in males and females. The results also provide further support for the involvement of a glutamatergic dysfunction in the pathogenesis of early-onset OCD.

Clinical features associated with treatment response in obsessive-compulsive disorder

Objective This study aims to investigate the effect of sociodemographic and clinical features on the short-term response to pharmacological treatment in obsessive-compulsive disorder (OCD). We focused especially on investigating factors previously associated with poorer prognosis, such as comorbidity with tic disorders, early onset of symptoms, and sensory phenomena preceding compulsions, which have been described as common in both tic-related and early-onset OCD. Method The study involved 41 consecutive adult patients with OCD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM-IV) criteria and was conducted at the OCD Spectrum Disorders Clinic of the University of Sao Paulo School of Medicine in São Paulo, Brazil, between January of 2000 and December of 2001. All patients were treated exclusively with oral clomipramine for 14 weeks. Treatment response, measured for Yale-Brown Obsessive-Compulsive Scale score decrease from baseline, was assessed by an investigator blinded as to the variables of interest present. Results Linear regression analysis showed that having a partner and sensory phenomena preceding compulsions were associated with better response to clomipramine treatment ( P = .04 and P = .002, respectively). Tic comorbidity and early onset of symptoms were not associated with poorer response. Conclusions In OCD, having a partner and sensory phenomena preceding compulsions seem to be associated with a favorable response to pharmacological treatment.

Comparison of treatment responses and clinical characteristics of early-onset and late-onset obsessive-compulsive disorder

Objective. The clinical characteristics and response to pharmacotherapy of adult patients with early-onset and late-onset obsessive-compulsive disorder (OCD) were compared in this study. Methods. A total of 50 outpatients with OCD diagnosed according to DSM-IV criteria (early-onset: 20; late-onset: 30) were included in the study. After initial clinical evaluation with The Structured Clinical Interview for DSM-IV/Clinical Version (SCID-I/CV), The Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), all patients were treated with fluvoxamine, sertraline or paroxetine for 12 weeks. Treatment response was defined as a ≥35% reduction in the Y-BOCS-total scores from baseline in a 12-week follow-up period. Results. Forty-three patients (early-onset: 16; late-onset: 27) completed the study. The early-onset group had higher frequencies of symmetry/exactness obsessions and ordering/arranging compulsions, and the late-onset group had higher mean age at assessment. Nine (56.3%) patients with early-onset and 18 (66.7%) with late-onset responded to pharmacotherapy. The difference between response rates was not statistically significant. Conclusions. Our study suggests that although there are some phenomenological differences between patients with early-onset OCD and late-onset OCD, these patients have similar responses to pharmacotherapy.

11C]DASB PET imaging of serotonin transporters in unmedicated patients with early onset obsessive compulsive disorder

11C]DASB PET imaging of serotonin transporters in unmedicated patients with early onset obsessive compulsive disorder

Fonctions exécutives dans le trouble obsessionnel compulsif : effet de l’âge de début des troubles

In obsessive-compulsive disorder (OCD), clinical, neurobiological and genetic differences have been reported according to age at onset (AAO). Given the importance of identifying homogeneous subtypes in complex hete-rogeneous disorders such as OCD, it would be particularly useful to identify a specific cognitive profile associated with early-onset OCD. Although impaired cognition has repea-tedly been demonstrated in OCD patients, discrepancies between studies have hampered the identification of a precise cognitive dysfunction. Executive dysfunction has often been reported, but findings have not always been replicated. The aim of this study was to assess executive functions in 30 patients according to their AAO. The sample consisted of 15 early-onset and 15 late-onset OCD patients and 22 normal controls, matched for age, sex and socio-economic status. Various aspects of executive function were assessed with five neuropsychological tests: Tower of London, Trail Making Test, Verbal Fluency, Design Fluency and Association Fluen-cy. The 30 OCD patients obtained lower total scores than the controls in the Tower of London test and association fluen-cy task (p<0.05 and p<0.001, respectively). Impairments were more marked for the early-onset group, with no effect of gender or age at interview. Deficits in specific aspects of frontal lobe function were found in the OCD group and were particularly pronounced within the early-onset group. These findings confirm clinical data suggesting that OCD patients can be subtyped according to age at onset and that OCD patients present unusual cognitive characteristics. They also support the hypothesis that early-onset OCD might be a rele-vant subgroup characterised both by a particular clinical profile and by specific cognitive characteristics.

Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in children and adolescents with obsessive–compulsive disorder

Dysfunction of the central serotonergic system has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The genetic contribution to the development of OCD is particularly high in early-onset OCD. The aim of this study was to investigate the effect of polymorphic variants in the gene of the novel brain-specific tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in OCD with disease onset in childhood and adolescence. We analysed two common single nucleotide polymorphisms (SNPs) of TPH2 in the putative transcriptional control region and in intron 2 of the TPH2 gene in a unique family-based sample of OCD patients with onset of the disease in childhood and adolescence comprising 71 complete, independent trios. The transmission disequilibrium test was used to determine transmission of alleles and haplotypes from parents to offspring. In this first study of TPH2 in OCD, analysis of the SNPs, rs4570625 and rs4565946, revealed a significant preferential transmission of haplotype G-C to children and adolescents with OCD. Moreover, a trend towards preferential transmission of the C allele of SNP rs4565946 to the patients was found. The genotype relative-risk estimate for homozygous C allele carriers of SNP rs4565946 was 2.58 (95% CI 0.98-6.82). In conclusion, the results link TPH2 variations to the pathogenesis of early-onset OCD and further support the aetiological relevance of 5-HT signalling in OCD.

Severe Obsessive-Compulsive Disorder With and Without Comorbid Hair Pulling

Chronic hair pulling and trichotillomania are putative obsessive-compulsive spectrum disorders. This study determined the prevalence of hair pulling in an inpatient obsessive-compulsive disorder (OCD) population and compared clinical characteristics and treatment response between subgroups with and without comorbid hair pulling. Patients with severe DSM-IV-diagnosed OCD (N = 154) who were consecutively admitted to an OCD residential treatment facility between August 2000 and July 2003 were included. Clinician-rated (Yale-Brown Obsessive Compulsive Scale) and patient-rated (Massachusetts General Hospital Hairpulling Scale, Beck Depression Inventory, and Posttraumatic Diagnostic Scale) measures were administered at index evaluation. OCD patients with and without moderate to severe hair pulling were statistically compared on clinical and treatment characteristics and treatment response. Of the OCD subjects, 18.8% (N = 29) endorsed any hair pulling, 15.6% (N = 24) had moderate to severe hair pulling, and 7.8% (N = 12) had severe hair pulling comparable to that of a specialty trichotillomania clinic population. OCD patients with moderate to severe hair pulling were more likely to be women (p < .001), endorse > 1 comorbid tic (p < .05), and have earlier-onset OCD (p = .001). This cohort also had fewer contamination obsessions (p = .04) and checking compulsions (p = .04) and was more likely to be receiving stimulant (p = .006) or venlafaxine (p = .02) medication than those patients without hair pulling. Posttraumatic Diagnostic Scale scores were nearly significantly higher in the OCD + hair pulling group (p = .08). OCD treatment response was unaffected by the presence of comorbid hair pulling. Hair pulling is a highly common comorbidity in severe OCD. Women and early-onset OCD patients appear to be more vulnerable to comorbid hair pulling. OCD sufferers with comorbid hair pulling also exhibit an increased risk for tics and may present with different OCD symptomatology.

Obsessive–compulsive disorder in elderly schizophrenia patients

Obsessive–compulsive disorder (OCD) has been identified in a substantial proportion of adult schizophrenia patients. Although symptoms of both disorders may persist into senescence, the prevalence of OCD in elderly schizophrenia patients has not yet been explicitly evaluated. We evaluated the prevalence of OCD in 50 elderly patients consecutively hospitalized for acute exacerbation of DSM-IV schizophrenia or schizoaffective disorder. The severity of schizophrenia and OCD symptoms was assessed using appropriate clinical rating scales. Eight (16%) of the 50 participants also met DSM-IV criteria for OCD. Schizophrenia patients with and without OCD did not differ significantly in demographic and clinical variables. In half of the schizophrenia–OCD group late onset OCD was observed, while in the remaining schizophrenia–OCD patients, early-onset OCD persisted into senescence, suggesting distinct mechanisms of occurrence. We conclude that OCD is not rare in elderly schizophrenia patients. Identification of this potentially treatable condition is imperative to provide adequate care.

Obsessive–compulsive disorder symptom dimensions show specific relationships to psychiatric comorbidity

The goals of this study were to examine relationships among symptom categories in obsessive–compulsive disorder (OCD), to establish OCD symptom dimensions by factor- and cluster-analytic analyses, and to explore associations between OCD symptom dimensions and comorbid neuropsychiatric conditions. A total of 317 OCD participants underwent a systematic diagnostic interview using the Structured Clinical Interview for DSM-IV. OCD symptoms assessed by the Yale–Brown Obsessive–Compulsive Scale Symptom Checklist ( N = 169) and by the Thoughts and Behaviors Inventory ( N = 275) were subjected to factor and cluster analyses. An identical four-factor solution emerged in two different data sets from overlapping samples, in agreement with most smaller factor-analytic studies employing the YBOCS checklist alone. The cluster analysis confirmed the four-factor solution and provided additional information on the similarity among OCD symptom categories at five different levels. OCD symptom dimensions showed specific relationships to comorbid psychiatric disorders: Factor I (aggressive, sexual, religious and somatic obsessions, and checking compulsions) was broadly associated with comorbid anxiety disorders and depression; Factor II (obsessions of symmetry, and repeating, counting and ordering/arranging compulsions) with bipolar disorders and panic disorder/agoraphobia; and Factor III (contamination obsessions and cleaning compulsions) with eating disorders. Factors I and II were associated with early onset OCD. This study encourages the use of cluster analyses as a supplementary method to factor analyses to establish psychiatric symptom dimensions. The frequent co-occurrence of OCD with other psychiatric disorders and the relatively specific association patterns between OCD symptom dimensions and comorbid disorders support the importance of OCD subtyping for treatment, genetic, and other research studies of this heterogeneous disorder.

Neuropsychological Functioning in Early- and Late-Onset Obsessive-Compulsive Disorder

Significant relationships have been noted between age of onset and demographics, clinical characteristics, and cerebral metabolic activity in obsessive-compulsive disorder (OCD). The authors investigated whether patients with early (N=21) and late (N=17) onset OCD differ with respect to neuropsychological functioning. Results revealed that the late onset OCD group obtained poorer scores on measures of executive function and auditory attention than the early onset group. Late onset OCD was also associated with poorer visual memory relative to healthy comparison subjects. These findings suggest that early and late onset OCD may be the result of at least partially differing neurobiological mechanisms.

Early‐onset obsessive‐compulsive disorder: a subgroup with a specific clinical and familial pattern?

The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender, comorbid conditions and familial risk of tics and OCD by studying a population consisting exclusively of patients with early-onset OCD. One hundred and forty-four patients having OCD were recruited in the study (108 early-onset probands and 36 late-onset probands). The early-onset probands and 199 of their first-degree relatives were investigated using structured interviews and questionnaires. This sample of early onset was mainly composed of children and adolescents (74 children and adolescents and 34 adults). The average age of onset of OCD is 9.98+/-3.2 years. Forty-four per cent of the probands have a comorbid tic disorder. The age-corrected morbid risk among the first-degree relatives is 17% for OCD and 12% for tics. Morbid risk for OCD and tics was independent of the presence of tics in probands. Only 32.6% of the probands have a positive family history of OCD. These findings are consistent with other reports in the literature that the morbid risk of OCD is elevated in relatives of probands with early-onset OCD. However, the majority of cases do not have a positive family history of OCD. This result suggests that early onset is not the only specific clinical marker for familial risk in OCD. Thus more work is needed to clearly elucidate other factors related to increased genetic vulnerability for OCD.

Familial and sporadic subtypes of early-onset Obsessive-Compulsive disorder

Family studies of Obsessive-Compulsive (OCD) indicate there is substantial heterogeneity in the familiality of the disorder. This study was done to determine whether there are differences between familial and sporadic probands with early-onset OCD in obsessive-compulsive (OC) symptom categories and comorbid psychiatric diagnoses. We ascertained 50 OCD probands ranging in age from 10 to 19 years with an onset of OC symptoms before age 15 years. All probands were directly assessed with semistructured diagnostic interviews; their first-degree and second-degree relatives were directly or indirectly assessed with similar diagnostic instruments. Descriptive data were compared in 33 familial and 17 sporadic OCD probands using logistic regression to control for age, gender, and age at onset of OC symptoms. Ordering compulsions were significantly more common in the familial OCD probands. Aberrant grooming behaviors were significantly more frequent in the familial subgroup with skin picking contributing significantly to that difference. Anxiety disorders other than OCD were also significantly more frequent in the familial subgroup with phobic disorders contributing significantly to that difference. The results indicate that familial and sporadic forms of early-onset OCD may be differentiated by ordering compulsions, aberrant grooming behaviors, and anxiety disorders other than OCD.

Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette’s syndrome

The hypothesis that common infections can modulate the onset and course of tic disorders and early-onset obsessive-compulsive disorder (OCD) in pediatric populations is longstanding. To date, most investigations have focused on the hypothesis of molecular mimicry and humoral immune responses. This study was carried out to investigate whether cytokines associated with the innate immune response or T cell activation were altered under baseline conditions and during periods of symptom exacerbation. Forty-six patients with Tourette's syndrome and/or early-onset OCD, aged 7-17 years, and 31 age-matched control subjects participated in a prospective longitudinal study. Ratings of clinical severity and serum were collected at regular intervals, and serum concentrations of 10 cytokines were measured repeatedly. Interleukin-12 and tumor necrosis factor alpha concentrations at baseline were elevated in patients compared with control subjects. Both of these markers were further increased during periods of symptom exacerbation. These findings suggest that symptom exacerbations are associated with an inflammatory process propagated by systemic and local cytokine synthesis that might involve the central nervous system. We conclude that, in the future, longitudinal studies of children with neuropsychiatric disorders should examine the involvement of innate and T cell immunity.

Admixture analysis of age at onset in obsessive–compulsive disorder

Age at onset (AAO) has been useful to explore the clinical, neurobiological and genetic heterogeneity of obsessive-compulsive disorder (OCD). However, none of the various thresholds of AAO used in previous studies have been validated, and it remains an unproven notion that AAO is a marker for different subtypes of OCD. If AAO is a clinical indicator of different biological subtypes, then subgroups based on distinct AAOs should have separate normal distributions as well as different clinical characteristics. Admixture analysis was used to determine the best-fitting model for the observed AAO of 161 OCD patients. The observed distribution of AAO in OCD is a mixture of two Gaussian distributions with mean ages of 11.1 +/- 4.1 and 23.5 +/- 11.1 years. The first distribution, defined by early-onset OCD, had increased frequency of Tourette's syndrome and increased family history of OCD. The second distribution, defined by late-onset OCD, showed elevated prevalence of general anxiety disorder and major depressive disorder. 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.

Brain-derived neurotrophic factor V66M polymorphism in childhood-onset obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is characterized by recurrent, intrusive, and disturbing thoughts, as well as by repetitive stereotypic behaviour. Insight into the senseless nature of the symptoms is generally preserved. Patients try, albeit usually unsuccessfully, to suppress the obsessive thoughts and compulsive behaviours. Acting out the stereotypic behaviours reduces the anxiety generated by the obsessions and compulsions (APA, 2000). In 60% of patients OCD develops before the age of 25 yr, and onset of disease can already occur in childhood (Flament et al., 1990). Familial loading is higher in early-onset OCD, indicating that genetic factors may be of greater importance in OCD with early onset (Pauls et al., 1995).

A family study of obsessive‐compulsive disorder with pediatric probands

Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown etiology. We examined the lifetime history of obsessions, compulsions, and OCD in the first- and second-degree relatives of 35 pediatric probands with OCD and 17 controls with no psychiatric diagnosis. All available first-degree relatives were directly interviewed blind to proband status with two semi-structured interviews. Parents were also interviewed to systematically assess the family psychiatric history of first- and second-degree relatives. Best-estimate lifetime diagnoses were made using all available sources of information. Data were analyzed with logistic regression by the generalized estimating equation method and with robust Cox regression models. The lifetime prevalence of definite OCD was significantly higher in case than control first-degree relatives (22.5% vs. 2.6%, P < 0.05). Compared to controls, case first-degree relatives also had significantly higher lifetime rates of obsessions and compulsions (both P < 0.05). There was no significant difference between case and control second-degree relatives in lifetime rates of OCD. First-degree relatives of case probands with ordering compulsions had a significantly higher lifetime rate of definite and subthreshold OCD than relatives of case probands without ordering compulsions (45.4% vs. 18.8%, P < 0.05). The lifetime prevalence of definite OCD was significantly higher in case first-degree relatives with a history of tics than in case first-degree relatives without a tic history (57.1% vs. 20.9%, P < 0.01). The results provide further evidence that early-onset OCD is highly familial and suggest that two clinical variables are associated with its familial aggregation.

Influence of age of onset on clinical features in obsessive-compulsive disorder

We compared early-onset and late-onset obsessive-compulsive disorder (OCD) patients in terms of demographic and clinical features. One hundred sixteen outpatients whose primary diagnosis was OCD according to DSM-IV diagnostic criteria were recruited. Early-onset (n=50) and late-onset (n=66) OCD groups were compared with respect to demographic variables and scores obtained on various scales. A male gender predominance was found in early-onset OCD group. Symmetry/exactness obsessions, religious obsessions, hoarding/saving obsessions, and hoarding/collecting compulsions also were significantly more frequent in the early-onset group than in the late-onset group. The results may suggest a phenotypic difference between the two groups. Further studies are needed to investigate the differences between early-onset and late-onset OCD groups to examine the hypothesis that early-onset OCD is a distinct subtype of the disorder.

A family study of early-onset obsessive-compulsive disorder

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.