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PubMed1999

Complex segregation analysis for obsessive compulsive disorder and related disorders.

Complex segregation analysis was applied to a sample of 107 Italian families with probands with obsessive compulsive disorder (OCD), using regressive logistic models to test for possible models of genetic transmission. We used two different phenotypic definitions of affection: 1) OCD; and 2) OCD plus Tourette's syndrome/chronic motor tics (CMT). Because of the potential relationship between OCD, Tourette's syndrome (TS), and other tic disorders, we considered these diagnoses to be determined by the same liability in subsequent steps of the analysis. For the 107 OCD families, the best fit was a dominant model of transmission (with a higher penetrance for females). When the phenotype boundaries were widened (OCD + CMT + TS), an unrestricted model of transmission became the best fit. We concluded that additional data are needed to support the hypothesis that Tourette's syndrome and OCD share a common etiology: on the basis of clinical and epidemiological considerations, the OCD phenotype probably presents a higher level of heterogeneity than the TS phenotype, and it could be regulated through different etiologic pathways.

Adolescent↗
PubMed1998

Computational model of obsessive-compulsive disorder: examination of etiologic hypothesis and treatment strategies.

Research has shown that obsessive compulsive disorder (OCD) is related to structural and functional abnormalities in the brain, and several authors have organized these findings into theories of OCD neuropsychiatric dysfunction. In this paper, these theories were used to develop a neural network model of OCD. OCD symptoms were hypothesized to result from a hyperactive orbitofrontal-striato-thalamic-orbitofrontal neural loop. The network was constructed and trained with a backpropagation algorithm, and it was then used to assess etiologic theories of OCD (e.g., basal ganglia dysfunction, inadequate dopaminergic inhibitory influence on basal ganglia and excessive input from the limbic system). The network was also observed in analogues of the treatment of OCD with serotonergic medications and behavior therapy. Results show that a) the network behaved both normally and abnormally, depending on what combinations of perceptual, motivational, and neurochemical inputs were presented to it; b) several etiologic mechanisms produced changes in the networks' behaviors similar to patients' subjective experiences of OCD symptoms; and c) different treatment strategies, both those modeled as pharmacologic and behavioral therapies, produced reductions in simulated OCD symptoms.

Algorithms↗
PubMed2000

Clinical correlates of obsessive compulsive disorder in children and adolescents referred to specialized and non-specialized clinical settings.

The objective of this study was to assess the extent of referral bias by comparing children and adolescents with Obsessive Compulsive Disorder (OCD) ascertained through a specialized pediatric OCD and a general child psychiatry clinic. Subjects were juveniles meeting DSM-III-R and DSM IV criteria for OCD referred to a general pediatric psychopharmacology clinic and to a specialized OCD clinic within the same academic medical center. Subjects were evaluated clinically and with structured diagnostic interviews using the Kiddie SADS-E. OCD was identified in 8.6% of the general psychiatry clinic subjects. The only differences between ascertainment sources in clinical or sociodemographic characteristics of OCD subjects were higher rates of social phobia and ADHD in the non-specialized clinic, while specialty clinic subjects had a greater lifetime severity of OCD and were more likely to have received treatment of their OCD. Because we found limited evidence for referral biases, our results suggest that findings from studies using either of these sources may generalize to the other. It also suggests that pooling subjects from the two sources is justified. Nevertheless, because some group differences did emerge, researchers should acknowledge referral bias as a potential limitation of their work.

Adolescent↗
PubMed1995

Obsessive compulsive disorder and mood disorders: a family study.

Obsessive compulsive disorder (OCD) often coexists with major depression (MD), with rates varying from 35 to 75%. The nature of the depressive symptomatology can be investigated by familial aggregation analysis, assuming that the disorder which occurs first is the one showing greater genetic liability and should have higher familial concentration. Therefore, the aim of our study was to assess the familial loading for OCD and mood disorders in the families of OCD patients with different chronology of onset for the mood disorder, to evaluate how the familial pattern of the diseases differs with different temporal sequences in which the two syndromes occur. A total of 172 OCD patients entered the study; 112 were pure OCD probands, 12 were unable to separate the onset of the two syndromes, 11 had prior mood disorder, and 37 of them had experienced their first depressive episodes after the onset of OCD. Information about the family history was collected by means of the Family History-Research Diagnostic Criteria (FH-RDC) and by directly interviewing at least 2 relatives per family. Morbidity risks for OCD indicate a familial concentration of the disorder in all groups, except the MD/OCD group. We found the highest rate of relatives affected by mood disorders in the families of patients with first onset of MD (28.8%), whereas in the other 3 groups MRs were much lower. These results suggest the affective nature of OCD patients who experienced first onset of MD. Thus, the chronology of onset seems to identify 2 different typologies of familial distribution.

Adult↗
PubMed2005

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.

Adolescent↗
PubMed2001

Social functioning and quality of life comparisons between obsessive-compulsive and schizophrenic disorders.

Treatment of obsessive-compulsive disorder has focused almost exclusively on symptom reduction; however, deficits in social functioning and quality of life of individuals with this disorder may contribute more to their "burden," suffering, and disability. To gauge the significance of social dysfunction and quality of life of persons with obsessive-compulsive disorder (OCD), we made comparisons with a group of persons with schizophrenia matched for age and gender. Thirty-one patients with OCD participating in a partial hospital treatment program were compared with 68 schizophrenic outpatients participating in a day rehabilitation program. The Independent Living Skills Survey (ILSS) and Lehman Quality of Life Scale (QOL) were administered before and after treatment for both cohorts. QOL scores were significantly lower for the OCD patients both before and after treatment, but improved significantly during treatment. OCD and schizophrenic patients had similar scores on almost every domain of the ILSS at pretreatment. The OCD patients improved significantly on many of the domains of social and independent living skills as a result of treatment and acquired significantly greater skills by post-treatment than did their counterparts with schizophrenia; however, the performance of social and independent living skills by OCD patients remained less than satisfactory even in domains where they improved. In the areas of job and leisure skills, there were significant group-by-time interactions. We concluded that patients with severe OCD and patients with schizophrenia are equally socially impaired. However, OCD patients experience greater significant functional improvement with multimodal treatment.

Activities of Daily Living↗
PubMed2000

Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder.

RATIONALE: Non-selective serotonin (5-HT) receptor agonists like meta-chlorophenylpiperazine and MK-212 have been used to explore the role of 5-HT in obsessive compulsive disorder (OCD). The results of these studies and the findings of autoradiography and neuroimaging studies, pointed to a possible role of the 5-HT1B/1D receptor in the pathophysiology of OCD. Recently the selective 5-HT1B/1D receptor agonist sumatriptan was used to further explore the role of the 5-HT1B/1D receptor in OCD. Equivocal results with respect to the increase of obsessive compulsive symptoms in patients with OCD were reported. In one study a significant increase in plasma growth hormone (GH) concentration was observed, although sumatriptan does not pass the blood-brain barrier. OBJECTIVES: In order to further explore the role of the 5-HT1B/1D receptor in the pathophysiology of OCD, we performed this study, following the same design as Ho Pian et al. (Psychopharmacology 140:365-370). METHODS: In the present study we performed a randomized, double-blind, placebo-controlled, cross-over design with zolmitriptan (5 mg per os), a selective 5-HT1B/1D receptor agonist with better brain penetrating properties than sumatriptan. RESULTS: We could not detect any changes in obsessive compulsive symptoms, mood, or anxiety levels, although we found a (nonsignificant) increase in plasma GH levels. CONCLUSIONS: Based upon these findings, no evidence was found for a specific role of the 5-HT1B/1D receptor in OCD. It should be noted, however, that challenge studies in OCD are difficult to perform. Perhaps in the future better challenge paradigms will make it possible to further explore the role of specific receptor types in OCD.

Adult↗
PubMed2003

Dopamine transporter density of basal ganglia assessed with [123I]IPT SPET in obsessive-compulsive disorder.

It has been suggested that dopamine, as well as serotonin, is associated with the pathophysiology of obsessive-compulsive disorder (OCD). Thus, many studies have been performed on brain regions associated with dopamine in patients with OCD. In the present study, we investigated the DAT density of the basal ganglia using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT) single-photon emission tomography (SPET) and evaluated the activity of the presynaptic dopamine function in patients with OCD. Fifteen patients with OCD and 19 normal control adults were included in the study. We performed brain SPET 2 h after the intravenous administration of [123I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific dopamine transporter (DAT) binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the specific/non-specific DAT binding ratio of the basal ganglia. Compared with normal control adults, patients with OCD showed a significantly increased specific/non-specific DAT binding ratio in the right basal ganglia and a tendency towards an increased specific/non-specific DAT binding ratio in the left basal ganglia. No significant correlation was found between the total scores on the Y-BOCS and the specific/non-specific DAT binding ratio of the basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia in patients with OCD could be involved in the pathophysiology of OCD.

Adolescent↗
PubMed2004

Obsessive-compulsive severity spectrum in the community: prevalence, comorbidity, and course.

OBJECTIVES: To describe lifetime prevalence rates, course and comorbidity of obsessive-compulsive disorder (OCD), obsessive-compulsive syndromes (OCS) and OC-symptoms (OC-sx) up to age 41. METHODS: In the Zurich community cohort study 591 subjects were selected after screening at the age of 19 and studied prospectively by 6 interviews from 20 to 40; they represent 1599 subjects of the normal population. The diagnoses of OCD met DSM-IV criteria. Course was assessed by graphic illustrations and prospective data. RESULTS: The lifetime prevalence rate was 3.5 % for OCD (males 1.7%, females 5.4 %) and 8.7 % for OCS (males 9.9%, females 7.5 %). The onset of OC-sx was 18 years (median); and in 70% before age 20. OCD was treated in one third of cases, OCS in 6.1%. The course of symptoms was chronic in 60%,but OCD and OCS showed in most cases considerable improvements over time. OCD reduced quality of life mostly in the subject's psychological wellbeing and at work but to a considerable extent also in other social roles. Comorbidity was prominent with bipolar disorder, panic disorder and social phobia and also significant with bulimia, binge eating, generalized anxiety disorder and suicide attempts; there was no association with substance abuse/dependence. CONCLUSION: OCD and OCD are manifestations of a wide spectrum of severity with high prevalence and strong clinical validity. The long-term course is better than generally assumed.

Adult↗
PubMed2005

Epidemiology and phenomenology of obsessive-compulsive disorder in non-referred young adolescents: a Polish perspective.

OBJECTIVE: The aim of this study was to investigate the frequency and phenomenology of obsessive-compulsive disorder (OCD) and subclinical OCD in a non-referred population of young Polish adolescents. METHOD: A two stage ascertainment procedure (school screening and diagnostic evaluation) was used to identify affected individuals. In the first stage, 3,100 pupils were asked to complete the Polish version of the 20-item Leyton Obsessional Inventory-Child Version (LOI-CV). In the diagnostic stage, the presence of obsessions and compulsions was assessed with the author's structured interview questionnaire based on DSM-IV and ICD-10 diagnostic criteria for OCD; the Polish version of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) was used to rate the symptom severity. RESULTS: A frequency of 0.38 % was found for OCD and 2.7 % for subclinical OCD. There was no significant difference in the phenomenology, demographic characteristic or socio-familial variables comparing the diagnosed OCD and subclinical OCD subjects. CONCLUSIONS: The identified OCD cases had characteristics similar to those of previously described clinical and non-referred samples.

Adolescent↗
PubMed2005

Group cognitive-behavior therapy with family involvement for middle-school-age children with obsessive-compulsive disorder: a pilot study.

OBJECTIVE: Middle-school-aged children with obsessive-compulsive disorder (OCD) are poised in development between the dependency of elementary-school-aged children and growing independence of adolescence. OCD patients of this age group may differ from older ones in the quality of symptoms and level of insight. We report the results of a naturalistic, pilot study of group Cognitive-behavior Therapy (CBT) for school-aged children with OCD with parents involved. The authors predicted symptom improvement and format acceptability. METHOD: Over a 1.5 year period, 14 children with OCD aged 8-14 years and their parents received 14-week group CBT based on March and Mulle's OCD in Children and Adolescents: A Cognitive-Behavioral Treatment Manual in three consecutive sessions of four to six families. Age of onset averaged 8.7 years, 36% had undergone at least one medication trial, and 36% had previous CBT experience. RESULTS: OCD symptoms measured by the Children's Yale-Brown Obsessive Compulsive Scale improved significantly, both statistically and clinically (25%) from moderate-severe to mild-moderate. Mean Clinical Global Impression of Impairment (NIMH-CGI) Impairment ratings fell from clinical to sub-clinical and CGI Improvement ratings were "much improved". Children's self-reported depression decreased significantly from pre- to post-group. Parent ratings of the negative impact of OCD symptoms on the Children's OCD Impact Scale and of behavior problems on the Child Behavior Checklist each improved significantly. CONCLUSIONS: This pilot study, which included a non-selected clinical sample, demonstrates that a manual-based treatment protocol may be effectively adapted for group treatment of different developmental levels and be exported for clinical use. Clinical improvement justifies further investigation in a controlled study.

Adolescent↗
PubMed1995

The utilization of nonpatient samples in the study of obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is increasingly studied in nonpatients, primarily through the selection of individuals who score high on a self-report measure of OCD. The usefulness of this methodology for understanding OCD presupposes that some of the individuals in the high-scoring group meet diagnostic criteria for OCD, that the obsessive-compulsive behaviors in the high-scoring individuals are stable across time to a certain degree, and that the features associated with OCD in patients also are found in the high-scoring nonpatients. Two studies are reported which provide support for these three assumptions. Together the studies suggest that OCD can be productively examined by the selection of individuals who score high on a self-report measure of OCD. Cautions in the use of this methodology for the study of OCD are also noted.

Adult↗
PubMed1993

Cocaine use and other suspected risk factors for obsessive-compulsive disorder: a prospective study with data from the Epidemiologic Catchment Area surveys.

Using prospectively gathered epidemiologic data, we sought to estimate the degree to which the risk of obsessive-compulsive disorder might be elevated among adults actively using cocaine, with and without illicit use of marijuana or other controlled substances. Study subjects were selected in 1980-84 by taking probability samples of adult household residents at five sites of the Epidemiologic Catchment Area (ECA) Program: New Haven, Connecticut; Baltimore, Maryland; St. Louis, Missouri; Durham-Piedmont, North Carolina; Los Angeles, California. Soon after sampling at baseline, a total of 18,572 participants completed standardized interviews to measure suspected risk factors (including illicit drug use) and to evaluate whether they had met diagnostic criteria for currently or formerly active obsessive-compulsive disorder (OCD), as well as other mental disorders. The interviews were re-administered 1 year later to identify incident cases among 13,306 at-risk participants, 414 being active cocaine users. After sorting these participants into strata defined by age and census tract of household residence and after excluding persons found at baseline to have active or prior OCD, we found 105 incident cases of OCD within 103 of the age-matched and residence-matched strata, which also contained a total of 514 subjects who had not developed OCD. Applying standard epidemiologic strategies presented in prior ECA research reports, we performed conditional multiple logistic regression to estimate the risk of OCD for active cocaine users versus non-users. We also performed unconditional multiple logistic regression to estimate OCD risk for the 414 active cocaine users versus the 12,892 participants not using cocaine. Both of these epidemiologic strategies yielded consistent results: subjects actively using cocaine and also marijuana were found to be at increased risk for OCD. Under the conditional model, the estimated relative risk was 7.2 (P = 0.03), while the value from unconditional regression was 4.1 (P = 0.01). Active users of cocaine almost always were active users of marijuana or some other controlled substance, so it was not possible to estimate a relative risk value for subjects using cocaine only. Nonetheless, if replicated, this epidemiologic test of the cocaine-OCD hypothesis warrants attention in laboratory and clinical research, as do other suspected risk factors identified in the study, including sex (being female), employment status (not working for pay) and a prior history of distinct psychiatric disorders such as alcohol dependence, affective disorders and phobic disorders.

Adolescent↗
PubMed2006

The semantic Simon effect in Tourette's syndrome and obsessive-compulsive disorder.

Core symptoms of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD) may be attributed to an impairment in inhibitory control. Neuropsychological studies have addressed inhibition in both disorders, but findings have been inconsistent. The aim of this study was to examine cognitive inhibition, using a semantic Simon effect paradigm, in patients with TS and OCD. Furthermore, to address comorbidity a group of TS+OCD patients was also examined. Results indicated that patients with TS and OCD were affected by the inhibitory components of the task. TS groups performed similarly to controls on simple and choice RT tasks, but were particularly compromised as increasingly complex inhibitory demands were imposed. OCD patients were slower and committed more errors than controls, especially in the more cognitively demanding conditions, and were particularly disadvantaged by incongruent stimulus-response compatibilities. Findings implicate possible fronto-striatal dysfunction, are consistent with previously reported inhibitory deficits in TS and OCD, and support the theory that comorbid TS+OCD is more closely linked to pure TS than OCD.

Cognition Disorders↗
PubMed2005

Impaired procedural learning in obsessive-compulsive disorder and Parkinson's disease, but not in major depressive disorder.

The striatum has been consistently implicated in the pathophysiology of obsessive-compulsive disorder (OCD), yet, studies assessing the performance of OCD patients in procedural learning tasks, assumed to rely on the intact functioning of the striatum, have yielded inconsistent results. Recently, Rauch et al. [Rauch SL, Savage CR, Alpert NM, Dougherty D, Kendrick A, Curran T, et al. Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning. J Neuropsychiatry Clin Neurosci 1997;9:568-73] have obtained evidence suggesting that seemingly intact performance of OCD patients in such tasks may be achieved by recruiting systems which in normal subjects are reserved for explicit or declarative, rather than implicit or procedural, processing. The present study assessed procedural learning in OCD patients using a card betting task in which explicit processing impairs, rather than assists, acquisition. In addition, we tested a group of Parkinson's disease (PD) patients, in order to better establish the dependence of the task on procedural learning, and a group of major depressive disorder (MDD) patients, in order to test the possibility that impaired learning in the card betting task may be a result of concurrent depression. The majority of OCD (15/18) and PD patients (14/16) did not acquire the task, whereas MDD patients acquired the task similarly to normal control subjects. These results demonstrate that OCD patients are impaired on a procedural learning task in which explicit processing impairs acquisition. Two different interpretations are suggested: that the striatal system is dysfunctional in OCD, or that inappropriate explicit processing in OCD interferes with the functioning of the striatal system.

Adult↗
PubMed2005

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2005

Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Several structural magnetic resonance imaging (MRI) studies have investigated the presence of brain abnormalities in obsessive-compulsive disorder (OCD) but have not produced consistent findings. This might be partly related to their use of a regions-of-interest approach. We assessed gray matter volumes in 19 OCD subjects and 15 healthy volunteers, using voxel-based morphometry (VBM). METHODS: Images were acquired with a 1.5-T MRI scanner, spatially normalized, and segmented with optimized VBM. Statistical comparisons were performed with the general linear model. RESULTS: Significant findings were detected in regions predicted a priori to be implicated in OCD, including increased gray matter in OCD subjects relative to control subjects in posterior orbitofrontal and parahippocampal regions; decreased gray matter in OCD patients in the left anterior cingulate cortex; and inverse correlations between obsessive-compulsive symptom severity and gray matter in the medial thalamus (p < .001, uncorrected for multiple comparisons). Also, an unpredicted site of gray matter reduction in OCD patients in the right parietal associative cortex approached significance (p = .052, corrected for multiple comparisons). CONCLUSIONS: Our findings are consistent with previous studies implicating dysfunction of orbitofrontal, cingulate, thalamic, and temporolimbic regions in OCD and suggest that the involvement of the parietal cortex in the pathophysiology of OCD warrants further investigation.

Adult↗
PubMed2006

Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.

Adult↗