Phenotypic differences in early- and late-onset obsessive-compulsive disorder

Early-onset forms of many medical diseases have been associated with specific genetic anomalies. To assess the potential marker value of onset age in obsessive-compulsive disorder (OCD), we examined and compared the phenotypic characteristics of patients with early and later onset. The study sample included 38 children with DSM-IV OCD and 129 adults 19 years of age or older, 77 of whom reported OCD onset prior to age 18 and 52 of whom reported OCD onset at 18 years of age or older. DSM-IV diagnoses were ascertained for all subjects using an amended version of the Diagnostic Interview for Genetic Studies (DIGS). An initial comparison of children and adults with childhood onset revealed several differences, including an earlier onset of clinically significant symptoms without impairment and earlier onset of DSM-IV OCD, a higher frequency of learning disabilities, and fewer obsessions and compulsions among our child patients. For this reason, subsequent analyses included only adult patients with early and later OCD onset. Nonimpairing symptom onset prior to puberty, a relatively aggressive course, and a greater number of obsessions and compulsions unrelated to the amount of time in illness characterized early-onset OCD. Later-onset OCD was characterized by nonimpairing symptom onset during puberty, a static course, and relatively few obsessions and compulsions that were variably related to the amount of time in illness. We conclude that children with OCD and adults with childhood onset differ in their report of clinical characteristics and should be analyzed separately in studies concerning the phenotypic characteristics of OCD. Early- and late-onset forms of OCD appear to be characterized by phenotypic features that have important neurobiologic and perhaps genetic implications.     

Is age at symptom onset associated with severity of memory impairment in adults with obsessive-compulsive disorder?

OBJECTIVE: Age at onset is a potentially important marker for neurobiological features of obsessive-compulsive disorder (OCD). This study examined the relationship between age at symptom onset and memory impairment in adults with OCD. METHOD: The authors used the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test to compare memory functioning of 37 adult OCD patients with self-reported childhood onset of symptoms (onset at less than 18 years of age) with that of 31 patients with adult-onset symptoms. RESULTS: No differences were found between the two groups on any of the verbal and nonverbal memory measures. CONCLUSIONS: Self-reported age at symptom onset is not associated with memory performance in adult patients with OCD according to tests previously found to be sensitive to frontal-striatal system dysfunction and impairment in OCD. Such dysfunction appears to be a consistent feature of OCD in adults, regardless of age at initial symptom onset.     

Early-onset obsessive-compulsive disorder and personality disorders in adulthood

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.     

The Brown Longitudinal Obsessive Compulsive Study: clinical features and symptoms of the sample at intake

OBJECTIVE: This article describes the method and intake findings of the Brown Longitudinal Obsessive Compulsive Study, the first comprehensive prospective investigation of the naturalistic course of obsessive-compulsive disorder (OCD) in a large clinical sample using longitudinal research methodology. METHOD: Intake data, collected between June 2001 and October 2004, are presented for 293 adult participants in a prospective, naturalistic study of OCD. Participants had a primary diagnosis of DSM-IV OCD and had sought treatment for the disorder. RESULTS: Our findings indicate that OCD typically has a gradual onset and a continuous course regardless of age at onset. There is a substantial lag between the onset of the disorder and initiation of treatment. OCD, which almost always coexists with other psychiatric symptoms, leads to serious social and occupational impairment. Compared with participants with late-onset OCD, early-onset participants had higher rates of lifetime panic disorder, eating disorders, and obsessive-compulsive personality disorder. The groups also differed on the types of obsessive-compulsive symptoms that were first noticed, as well as on rates of current obsessions and compulsions. CONCLUSION: The demographics, clinical characteristics, comorbidity rates, and symptom presentation of the sample are consistent with those reported for cross-sectional studies of OCD, including the DSM-IV Field Trial. The current sample has a number of advantages over previously collected prospective samples of OCD in that it is large, diagnostically well characterized, recruited from multiple settings, and treatment seeking. This unique data set will contribute to the identification of meaningful phenotypes in OCD based on stability of symptom dimensions, prospective course patterns, and treatment response.     

Phenotypic characteristics of Obsessive-Compulsive Disorder ascertained in adulthood.

Over the past decade, the increased awareness and knowledge of Obsessive-Compulsive Disorder (OCD) has allowed the in-depth study of its phenotypic characteristics. The largest studies to date have described the symptom and syndrome characteristics of treatment-seeking patients. While usefully homogeneous with regard to their current state, the clinical characteristics of patients seeking treatment may only partially represent the OCD population. We report findings from 100 self-selected volunteers at various stages of their OCD illness who were participating in a genetic study. Many similarities with past reports were found, including high rates of mood disorder, significantly more mood disorder in females as compared with males, and increased social impairment among males despite an equal amount of time in episodes of disorder. On the other hand, mean age of onset in this nontreatment seeking population was younger. Lifetime rates of obsessions and compulsions in this population were substantially higher than previous reports, suggesting that the content of obsessions and compulsions shifted over time, and evolved into a lifetime repertoire. Furthermore, a separate analysis of the age of clinically significant O-C symptom onset without impairment revealed that males and females did not differ, suggesting that previous reports of earlier onset age in males may actually reflect earlier onset of impairment. Future genetic studies may benefit from the analysis of both significant O-C symptom onset, as well as the onset of full-syndromal OCD. These findings may suggest phenotypic characteristics that define homogeneous subgroups of patients with OCD.     

Neural bases of the clinical and neurocognitive differences between early- and late-onset obsessive–compulsive disorder

BackgroundUsing biological evidence to define subtypes within the heterogeneous population with obsessive–compulsive disorder (OCD) is important for improving treatment response. Based on age at onset, OCD can be clustered into 2 groups, each of which is more homogeneous with respect to clinical and cognitive phenotype. However, the neural bases for these phenotypic differences need to be established to construct evidence-based homogeneous groups.MethodsWe compared brain volumes, clinical symptoms, and neurocognitive function for 49 people with early-onset OCD and 52 with late-onset OCD (participants in both groups were unmedicated or drug-naïve), and 103 healthy controls. We performed regression analyses to examine group × volume interaction effects on clinical outcomes or neurocognitive function in people with OCD.ResultsWe observed larger volumes in the precentral, orbitofrontal, middle frontal, and middle temporal gyri in people with early-onset OCD compared to those with late-onset OCD. Poorer visuospatial construction in early-onset OCD was correlated with a larger left middle frontal gyrus volume. Impaired visuospatial memory in people with early-onset OCD and cognitive inflexibility in people with late-onset OCD were correlated with increased and decreased volume in the left middle frontal gyrus, respectively. We found group × volume interactions for obsessive–compulsive symptom scores in the left middle temporal gyrus of people with OCD.LimitationsAlthough we divided the subtypes using the commonly adopted criterion of age at onset, this criterion is still somewhat controversial.ConclusionWe provided the neural bases for clinical and neurocognitive differences to demonstrate that biological evidence underlies the distinctions between early- and late-onset OCD. This study suggests that different treatment options should be considered for the OCD subtypes, because their neurobiology differs and is related to distinct phenotypic profiles.     

Genetic findings in obsessive-compulsive disorder in childhood and adolescence and in adulthood

Obsessive-compulsive disorders (OCD) are on the rise, and affected children, 1-2% of the general population, often are seriously impaired in their development. OCD is characterized by recurrent, intrusive and disturbing thoughts as well as by repetitive stereotypic behaviours. Depending on their age and developmental status, patients usually try unsuccessfully to suppress the obsessive thoughts and compulsive behaviours. The current state of genetic research on OCD and early-onset OCD is presented and discussed. OCD, especially early-onset OCD, has been shown to be familial. Convincing evidence indicates that both environmental and genetic factors substantially influence OCD. Various approaches, including linkage and association studies, yielded conflicting results as well as the notion that multiple genes of modest effect sizes, in interaction with environmental factors, cause vulnerability to the disorder. The phenotypic and genetic heterogeneity of OCD complicate the identification of specific genetic factors. Further studies have to be designed in consideration of subtypes, e.g. age at onset, symptom dimensions, or comorbid disorders.     

Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies.     

Phenomenology associated with age at onset in patients with bipolar disorder at their first psychiatric hospitalization

OBJECTIVE: To compare the clinical presentation of patients with early-onset (age <18 years) and typical-onset (age 20-30 years) bipolar disorder at the time of first hospitalization. METHODS: Patients, aged 12-45 years at their first psychiatric hospitalization, with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were evaluated on measures of manic, depressive, and positive psychotic symptoms. Differences in symptom profiles between early- and typical-onset groups were examined. RESULTS: One hundred three early-onset and 58 typical-onset patients were compared. Mixed episodes were more common in the early-onset group, while psychotic features and current substance use were more common in the typical-onset group. There was no significant difference in manic symptom severity ratings between early- and typical-onset groups (F = 1.8, df = 11, 144, p = 0.06). However, these groups differed in depressive (F = 4.2, df = 16, 139, p < 0.001) and positive psychotic (F = 2.8, df = 16, 139, p = 0.001) symptom profiles. Typical-onset bipolar patients reported more severe weight loss and formal thought disorder compared with early-onset patients. CONCLUSIONS: Depressive and positive psychotic symptoms may differ in association with age at onset among patients with bipolar disorder. Additional studies are necessary to determine whether homogeneous phenotypes of bipolar disorder can be delineated based upon age at onset.     

Subtyping obsessive-compulsive disorder: clinical and immunological findings in child and adult onset

It has been suggested that certain kinds of childhood OCD with specific clinical, biological and immunological characteristics may form a subgroup of OCD. We study the presence of these characteristics in child onset OCD and propose that the disorder be considered as a subtype of adult OCD. Forty adult patients with OCD were divided in two groups according to time of disease onset: 18 early onset and 21 late. Both sets were compared with a control group of 14 psychiatric patients. Child onset OCD was associated with higher mean ASLO titers, higher frequencies of history of tic disorders and tonsillitis in childhood and compulsive symptoms. No differences were found in D8/17 antibody titers or in other autoimmune parameters. The findings suggest that child onset OCD can be considered as a subgroup of adult OCD, although more specific biological markers are needed to identify it.     

Symptom structure in Japanese patients with obsessive-compulsive disorder

OBJECTIVE: Obsessive-compulsive disorder (OCD) comprises a number of specific symptom dimensions. The authors factor analyzed data on the Yale-Brown Obsessive Compulsive Scale symptom checklist in a large group of Japanese OCD patients to examine whether symptom dimensions were stable across cultures. METHOD: A principal components analysis of Yale-Brown Obsessive Compulsive Scale major symptom categories was performed on Japanese OCD patients (N=343). The association between symptom dimensions and clinical variables, including 1-year outcome after combination treatment, was also examined using Pearson correlations. RESULTS: Four factors explaining 57.7% of the variance were identified: 1) contamination/washing, 2) hoarding, 3) symmetry/repeating and ordering, and 4) aggressive/checking symptoms. The symmetry dimension was associated with early age at onset, and both the symmetry and hoarding dimensions were associated with decreased functioning and treatment resistance. CONCLUSIONS: The findings in this study support transcultural stability in the symptom structure of OCD, which is consistent with the hypothesis that OCD is mediated by universal psychobiological mechanisms.     

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.     

Alexithymia in obsessive-compulsive disorder: clinical correlates and symptom dimensions

Previous studies have indicated that obsessive-compulsive disorder (OCD) is associated with alexithymic traits. The purpose of the current study was to evaluate the difference of alexithymia in OCD patients and healthy controls. This study was also designed to elucidate a specific link between certain OCD symptom dimensions and alexithymia. Forty-five patients with OCD and 45 healthy controls completed measures of the OCD symptom severity, alexithymia, anxiety, and depression. Patients with OCD had significantly higher scores of alexithymia than did the healthy controls. Multiple regression analysis revealed that age at onset and the level of anxiety were significantly associated with alexithymia. "Sexual/religious obsessions" was the only symptom dimension that showed a positive association with alexithymia in OCD patients. These findings suggest that OCD patients with a high level of anxiety and an early age of onset may have greater alexithymic tendency. We also found the first evidence for a specific link between sexual/religious obsessions and alexithymia in patients with OCD.     

Citalopram intravenous infusion in resistant obsessive-compulsive disorder: an open trial

BACKGROUND: Treatment with intravenous clomipramine is rapidly effective in some obsessive-compulsive disorder (OCD) patients unresponsive to orally administered serotonin reuptake inhibitors (SRIs). The selective serotonin reuptake inhibitor citalopram is effective for OCD when administered orally. We investigated whether intravenous citalopram would rapidly benefit OCD patients unresponsive to orally administered SRIs. METHOD: Thirty-nine adult outpatients participated in a 3-week open-label trial of intravenous citalopram. Eligible patients had moderate-to-severe DSM-IV OCD of > or = 1 year's duration, a baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) score > or = 25, and no other active Axis I diagnosis and had failed at least 2 adequate oral SRI trials, excluding citalopram. Intravenous citalopram was administered daily for 21 days, followed by oral citalopram until treatment day 84. Intravenous citalopram was started at 20 mg/day and was increased to 40 to 80 mg/day as tolerated. RESULTS: Intravenous citalopram was well tolerated even at higher doses (dropout rate = 2.6%). At day 21, 23 (59%) of the 39 patients had YBOCS score decreases of > or = 25%, of whom 4 had decreases of > or = 35%. Twenty-seven patients with YBOCS score decreases of > or = 20% were allowed to continue on treatment with oral citalopram, and by day 84, all had substantial further improvement. All 27 patients also showed significant improvement in several dimensions of quality of life. CONCLUSION: Intravenous citalopram was safe and rapidly effective in a group of treatment-resistant OCD patients. The early onset of response suggests a means of accelerating OCD symptom relief and predicting response to oral citalopram treatment. Double-blind, double-dummy, placebo-controlled trials of intravenous versus oral citalopram in patients with treatment-resistant OCD are indicated.     

Genetic factors in obsessive-compulsive disorder: summary of genetic studies

Obsessive-compulsive disorder (OCD) affects children and adults. As in most psychiatric disorders, genetic and environmental factors play an important role in the development of OCD. The symptom onset occurs at early age (before 18 years) in 80% of the cases; this early onset OCD has different clinical features compared to the adult form. Family studies suggest that childhood onset OCD is more heritable. In addition, there is male preponderance and a higher rate of comorbid tic and attention deficit hyperactivity disorder in the early onset OCD. These data imply that the early onset OCD might have different etiological background. In this review article we will shortly describe OCD symptoms, possible endophenotypes and neurobiological theories. After an overview of the applied genetic methods, we will summarize the genetic results of the OCD literature, especially candidate gene association studies. Finally, we will outline the possible future trends in psychiatric genetics.     

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.     

Comparison of adult manifestations of schizophrenia with onset before and after 15 years of age

We examined 19 adult cases of early-onset schizophrenia (onset before age 15) and 19 controls (schizophrenia with onset between age 15 and 35). Being matched by sex, length of hospitalization and living environment while the present age between groups showed no difference, patients were compared on psychopathological symptom measures and intelligence quotient (IQ). Results showed that early-onset cases scored significantly higher on Scales for the Assessment of Negative Symptoms and had lower performance IQ. No group difference in positive symptoms measure from Brief Psychiatric Rating Scale and full IQ was noted. It suggested that when early-onset patients grew up, phenomenologically, they resembled the schizophrenia of usual early-adult onset in the positive symptom dimension, but with more negative symptoms, which may be fundamental in this group of patients.     

Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study

OBJECTIVE: Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects. METHOD: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping. RESULTS: Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed.     

Lost human capital from early-onset chronic depression

OBJECTIVE: Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. METHOD: The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. RESULTS: Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. CONCLUSIONS: Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.