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Tic-related vs. non-tic-related obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a chronic condition characterized by an array of intrusive, upsetting thoughts and interfering, repetitive behaviors. Some forms of OCD may be etiologically related to Tourette's syndrome (TS). This cross-sectional study examines a range of obsessive compulsive (OC) symptoms which have been hypothesized to distinguish tic-related OCD from non-tic-related OCD. One hundred and seventy-seven patients with a primary DSM-IIIR diagnosis of OCD, aged 16 to 72, participated in the study. Patients with tic-related OCD (n = 56) reported more OC symptoms, including more aggressive, religious, and sexual obsessions as well as checking, counting, ordering, touching, and boarding compulsions than did patients with non-tic-related OCD (n = 121). Contrary to our expectation, these two groups of OCD patients did not differ with regard to the presence of "just right" phenomena or symptoms of psychasthenia. "Just right" phenomena and symptoms of psychasthenia, however, were both found to be associated with the current severity of OC symptoms.

Adult↗

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder.

BACKGROUND: Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits. METHOD: A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment. RESULTS: At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus. CONCLUSIONS: OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striato-pallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.

Brain Diseases↗

[Self-assessment questionnaire of alcoholic craving (ECCA Questionnaire: Behavior and Cognition in Relation to Alcohol: French translation and validation of the Obsessive-Compulsive Drinking Scale].

Clinical, neurobiological and neuropsychological hypotheses suggest that the dimension of alcohol craving includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking. Anton et al. (1995) developed a 14 items self-rating scale, the Obsessive Compulsive Drinking Scale (OCDS) which includes items for assessing three dimensions: global, and the obsessive and the compulsive subdimensions. In this study, we included 156 patients, 105 men and 51 women, who met DSM IV diagnostic criteria for alcohol dependence. The mean age of our population was 39.1 +/- 11.2 years without difference between sexes. We did not found any correlation between the CAGE score and the OCDS total score or the obsessive and compulsive subscores (respectively, r = .15, r = .10 et r = .18). Moreover, we did not found any correlation between OCDS scores and mean daily alcohol consumption (r = .18, r = .16, r = .19). This could indicate that the dimension measured by the scale was somewhat independent of actual drinking. As such, it might act as an independent measure of the "state of illness" for alcohol-dependent patients. The test-retest correlation for the OCDS total score was .95 and the obsessive and compulsive subscales test-retest correlations were .93 and .89 respectively. The internal consistency of the items of the OCDS was high (alpha = .89). Principal component analysis had identified in the french version of the OCDS, three factors accounting for 63.5% of the total variance. These results indicate that the french version of the OCDS seems to validly measure a dimension of alcohol dependence. The ease of administration, reliability, and concurrent validity of the OCDS makes it particularly useful as an outcome measurement tool for various clinical therapeutic protocols in alcoholism.

Adult↗

Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is characterized by both motor and phonic tics. One half to two thirds of children with TS experience a reduction or complete resolution of tic symptoms during adolescence. At least one third of adults with TS have comorbid obsessive-compulsive disorder (OCD). OBJECTIVES: To clarify the clinical course of tic and OCD symptoms in children with TS and determine if baseline clinical measurements in childhood are associated with future symptom severity in late adolescence and early adulthood. DESIGN: Prospective cohort study. SETTING: Yale Child Study Center tic and OCD outpatient specialty clinic. PARTICIPANTS: Forty-six children with TS who received a structured clinical evaluation prior to age 14 years. MAIN OUTCOME MEASURES: Expert-rated tic and OCD symptom severity at follow-up interview an average of 7.6 years later (range, 3.8-12.8 years). RESULTS: Eighty-five percent of subjects reported a reduction in tic symptoms during adolescence. Only increased tic severity in childhood was associated with increased tic severity at follow-up. The average age at worst-ever tic severity was 10.6 years. Forty-one percent of patients with TS reported at one time experiencing at least moderate OCD symptoms. Worst-ever OCD symptoms occurred approximately 2 years later than worst-ever tic symptoms. Increased childhood IQ was strongly associated with increased OCD severity at follow-up. CONCLUSION: Obsessive-compulsive disorder symptoms in children with TS became more severe at a later age and were more likely to persist than tic symptoms.

Adolescent↗

Signs of central nervous system dysfunction in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has been linked to altered neurological function following head trauma, encephalitis, abnormal birth events, and Gilles de la Tourette's syndrome. Abnormalities in computed tomographic scans, electroencephalograms, positron emission tomographic scans, and evoked potentials have been described in this disorder, but are neither consistent nor pathognomonic of OCD. Neurological soft signs are nonlocalizing signs of deviant performance on a motor or sensory test where no other sign of a neurological lesion is present. We studied 41 medication-free patients with OCD who met DSM-III-R criteria, as well as 20 normal controls, matched for age, sex, and handedness, on 20 individual tasks that involved fine motor coordination, involuntary movements, and sensory and visuospatial function. There were significantly more signs of central nervous system dysfunction in the OCD group, as shown by abnormalities in fine motor coordination, involuntary and mirror movements, and visuospatial function. An excess of findings on the left side of the body and abnormalities of cube drawing may suggest right hemispheric dysfunction in a subgroup of patients with OCD. Soft signs correlated with a severity of obsessions. There was also a correlation between abnormalities in visual memory and recognition on neuropsychological testing and total soft signs. These findings provided additional evidence for a neurological deficit in some patients with OCD. However, further comparisons with other psychiatric populations are needed to determine whether these findings are unique to OCD or are a property of other psychiatric disorders as well.

Adolescent↗

A 2- to 7-year follow-up study of 54 obsessive-compulsive children and adolescents.

OBJECTIVE: Due to the generally poor prognosis previously reported for patients with obsessive-compulsive disorder (OCD), this report systematically assessed the outcome of patients who had had access to new psychopharmacologic treatments to determine whether there had been any long-term gains and if there were any predictors of outcome. DESIGN: Prospective follow-up study of a cohort of consecutive pediatric patients with OCD who had participated in controlled treatment (clomipramine hydrochloride) trials and then received a variety of interim treatments. PATIENTS: Fifty-four children and adolescents were reevaluated 2 to 7 years (mean, 3.4 +/- 1.0 years) after initial clomipramine treatment. Information for 48 (89%) of the patients was from direct interview and for the remaining six (11%) from at least two sources. RESULTS: On follow-up, 23 of the subjects (43%) still met diagnostic criteria for OCD, and only three (6%) could be considered in true remission. Thirty-eight subjects (70%) were taking psychoactive medication at the time of follow-up. Although OCD symptoms continued, the group as a whole was significantly improved at follow-up, with only 10 subjects (19%) rated as unchanged or worse. A worse OCD outcome score at follow-up was predicted in a stepwise multiple regression by (1) more severe OCD symptoms score after 5 weeks of clomipramine therapy, (2) lifetime history of a tic disorder, and (3) presence of parental Axis I psychiatric diagnosis (R2 = .31, P < .01). CONCLUSIONS: With new treatments available, most patients with pediatric OCD can expect significant longterm improvements but not complete remission. This study supports previous reports of the chronicity and intractability of the disorder, as there still remained a significant subgroup of subjects who exhibited continued morbidity despite multiple interventions.

Adolescent↗

Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder.

BACKGROUND: Abnormalities in frontostriatal circuits have been implicated in obsessive-compulsive disorder (OCD). Although OCD commonly emerges during childhood or adolescence, few studies have examined frontostriatal anatomy in psychotropic-naive children with OCD near the onset of illness to determine the possible role of atypical developmental processes in this disorder. METHODS: Magnetic resonance imaging scans from 19 children with OCD who had not been exposed to psychotropic drugs, aged 7 to 18 years, and 19 case-matched healthy control subjects were analyzed to determine the volumes of the following structures: prefrontal cortex, striatum (caudate and putamen), lateral and third ventricles, and intracranial volume. RESULTS: Patients with OCD had significantly smaller striatal volumes and significantly larger third ventricle volumes than controls, but did not differ in prefrontal cortical, lateral ventricular, or intracranial volumes. Striatal volumes were inversely correlated with OCD symptom severity but not illness duration. CONCLUSIONS: Our findings provide new evidence of abnormalities of the striatum in pediatric OCD. These results are preliminary, given the small sample size.

Adolescent↗

Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls.

BACKGROUND: The neuropsychological dysfunction associated with obsessive-compulsive disorder (OCD) has similarities to the deficits reported in other affective or anxiety disorders. We directly compared cognitive function in patients with OCD with that in matched patients with unipolar depression and panic disorder and healthy control subjects to establish the specific nature of neuropsychological deficits in OCD. METHODS: Thirty patients with OCD, 30 patients with panic disorder, 20 patients with unipolar depression, and 30 controls completed a computerized neuropsychological battery that assessed the accuracy and latency of executive, visual memory, and attentional functions. RESULTS: The groups did not differ according to age, years of education, or estimated IQ. However, we found group differences in cognitive performance. The patients with OCD were impaired on measures of spatial working memory, spatial recognition, and motor initiation and execution. In contrast, performance of these tasks by patients with panic disorder or depression did not differ from that of controls. There were no group differences for performance on the measures of planning, cognitive speed, pattern recognition, and delayed matching to sample, although patients with depression were impaired for attentional set shifting. CONCLUSIONS: Neuropsychological deficits were observed in patients with OCD that were not observed in matched patients with panic disorder or unipolar depression. As such, the cognitive dysfunction in OCD appears to be related to the specific illness processes associated with the disorder.

Adult↗

Multicenter double-blind comparison of sertraline and desipramine for concurrent obsessive-compulsive and major depressive disorders.

BACKGROUND: Serotonin reuptake inhibitors (SRIs) have demonstrated consistent efficacy in the treatment of obsessive-compulsive disorder (OCD), while agents that are primarily norepinephrine reuptake inhibitors have not. Comparable efficacy has been demonstrated for SRI and non-SRI antidepressants in uncomplicated major depressive disorder (MDD). This multicenter trial is the first comparison of an SRI (sertraline) and a non-SRI antidepressant (desipramine) in the treatment of OCD with concurrent MDD. METHODS: One hundred sixty-six patients diagnosed using structured clinical interviews and recruited from 16 treatment sites were randomly assigned to double-blind treatment with either sertraline (up to 200 mg/d) or desipramine (up to 300 mg/d) over 12 weeks. Measures of severity of OCD and MDD symptoms, as well as adverse effects of the medications, were monitored over the course of the treatment period. RESULTS: Patients assigned to sertraline responded significantly better at end point on measures of OCD and MDD symptoms compared with patients assigned to desipramine. Sertraline was also associated with a significantly greater number of patients who achieved a "robust" improvement in OCD symptoms (> or =40% reduction) compared with desipramine. More patients receiving desipramine than sertraline discontinued treatment because of adverse events. CONCLUSIONS: The SRI sertraline was more effective in reducing MDD and OCD symptoms than the primarily norepinephrine reuptake inhibitor desipramine for patients with concurrent OCD and MDD.

Adrenergic Uptake Inhibitors↗

Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders.

BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders. METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.

Adult↗

Mapping structural brain alterations in obsessive-compulsive disorder.

BACKGROUND: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. OBJECTIVE: To describe the structural brain alterations detected in the magnetic resonance images of a large series of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of volume changes throughout the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72 age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences were obtained in all participants. A statistical parametric mapping approach was used to delineate possible anatomical alterations in the entire brain. To preserve volumetric information, voxel values were modulated by the Jacobian determinants (volume change measurement) derived from spatial normalization. MAIN OUTCOME MEASURES: Voxelwise brain volumes. RESULTS: The brains of patients with OCD showed reduced gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex, and the left insulo-opercular region. A relative increase in gray matter volume was observed bilaterally in the ventral part of the putamen and in the anterior cerebellum. All these brain alterations were abnormally correlated in patients with OCD, and age statistically significantly contributed to the relative enlargement observed in the striatal areas. Disease severity, the nature of symptoms, and comorbidities were not related to the changes described. Nevertheless, patients with prominent aggressive obsessions and checking compulsions showed reduced amygdala volume in the right hemisphere. CONCLUSIONS: The pattern of anatomical features depicted by this voxelwise approach is consistent with data from functional studies. The reported anatomical maps identified the specific parts of the frontostriatal system that were altered in patients with OCD and detected changes in anatomically connected distant regions. These data further define the structural brain alterations in OCD and may contribute to constraining the prevailing biological models of this psychiatric process.

Adolescent↗

Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder.

CONTEXT: 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. OBJECTIVE: To determine whether genotypes at polymorphisms in the SLC1A1 gene region are associated with early-onset OCD. DESIGN: Family-based analysis of association using the transmission disequilibrium test, confirmed using the family-based association test. SETTING: Anxiety disorders program in an academic medical center. PARTICIPANTS: Seventy-one probands with DSM-III-R or DSM-IV OCD and their parents. METHODS: Nine single nucleotide polymorphisms spaced throughout the SLC1A1 gene region were genotyped. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder.

Probands affected with eating disorders (ED) present a higher number of relatives affected with obsessive-compulsive disorders/tic disorders than a comparison population. Therefore, we hypothesized that ED and obsessive-compulsive disorder (OCD) might share the same biological liability, and that a single major gene might account for that liability. We tested this hypothesis by applying a complex segregation analysis to 141 families of probands affected with ED (89 with anorexia nervosa, restricting and binge-eating types, 52 with bulimia nervosa). Given the hypothesized relationship between OCD and genetic spectrum disorders, we considered these diagnoses as affected phenotype in relatives. In Italian ED families, ED and OCD followed a Mendelian dominant model of transmission. When probands were divided according to co-diagnosis of OCD, best fit in the subgroup of families of 114 probands without OCD co-diagnosis was for a Mendelian dominant model of transmission whereas a Mendelian additive model of transmission represented best fit in the subgroup of families of 27 probands with an OCD co-diagnosis. Genetic transmission was not shown in those families where the only affected phenotype was ED. The existence of a Mendelian mode of genetic transmission within ED families supports the hypothesis that a common genetic liability could account for both ED and OCD.

Adult↗

Three types of obsessive compulsive disorder in a community sample.

Until recently, prior estimates of the prevalence of obsessive compulsive disorder (OCD) have been based on clinical data. The present investigation studied point prevalence and demographic data that pertain to three ritual-based forms of OCD in a sample of the adult general population of the greater St. Louis area. Two hundred fifty male and 247 female subjects were administered a structured interview designed to identify the presence of symptoms associated with OCD according to DSM-III criteria. The overall prevalence rate of OCD was 2.8%. The most prevalent form of OCD involved checking (1.6%), followed by a miscellaneous category that included repeating, counting and collecting rituals (1.0%) and, finally, washing compulsions (.8%). Subjects with OCD did not differ demographically from the rest of the sample except that they were more likely to live in the city. Results indicate that OCD is more prevalent than previously supposed and that checking compulsions may be the most common form of ritual in nonclinical samples.

Adult↗

Additional evidence that genetic variation of MAO-A gene supports a gender subtype in obsessive-compulsive disorder.

Studies have recently reported a sexually dimorphic association between obsessive-compulsive disorder (OCD) and a polymorphism related with variations in MAO-A activity. These observations suggest the possibility of gender differences in genetic susceptibility for OCD. We thus reexamined the MAO-A/EcoRV polymorphism in a sample of 122 OCD patients and 124 healthy subjects. An excess of allele 1 in OCD females with major depression disorder was confirmed as previously reported. This difference was more strongly associated with OCD females than males in the total sample. Finally, we analyzed a sample of 51 OCD trios. Haplotype-based haplotype relative risk (HHRR) analysis of the inheritance of the MAO-A variants revealed in the female probands that 14 out of 19 transmitted the allele 1, providing significant evidence for an allelic association between OCD and MAO-A gene. In conclusion, our findings may provide molecular evidence to identify a clinically meaningful gender subtype. However, an effort should be made to replicate the analysis in larger samples of informative parents using strategies such as transmission disequilibrium test to allow definite conclusions.

Adult↗

Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family-based association study of 55 trios. Extended transmission-disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene (P = 0.005). Moreover, in a population-based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically-matched controls (P = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family- and population-based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms.

Adolescent↗

Diagnostic interview assessed neuropsychiatric disorder comorbidity in 334 individuals with obsessive-compulsive disorder.

Is obsessive-compulsive disorder (OCD) a discrete disorder? Three hundred thirty-four individuals with OCD were interviewed using the Structured Clinical Interview for DSM (SCID). Results demonstrate that OCD is highly comorbid with other neuropsychiatric disorders, with 92% of OCD study participants receiving one or more additional Axis I DSM diagnoses. Among these additional diagnoses, lifetime mood disorders (81%) and anxiety disorders (53%) were the most prevalent. With the exception of substance-related disorders and specific phobias, all disorders assessed were found in considerably higher frequency than in the general population, indicating that OCD is associated with highly complex comorbidity. These data have implications for genetic studies of OCD and disorders related to OCD, as well as for specific psychotherapeutic and psychopharmacologic interventions.

Adult↗

Morphometric alterations of anterior superior temporal cortex in obsessive-compulsive disorder.

The superior temporal gyrus (STG) may be involved in the pathophysiology of obsessive-compulsive disorder (OCD). Moreover, the anterior STG has rich interconnections with the orbitofrontal cortex and the amygdala, and plays a role in visuospatial processing, which is impaired in patients with OCD. This study was designed to examine the morphological abnormalities of the anterior STG and their relationships with visuospatial function and clinical symptom in patients with OCD. We measured gray matter volumes of the anterior STG [rostral STG and planum polare (PP)] by three-dimensional (3D) magnetic resonance imaging in age- and sex-matched groups, which consisted of 22 patients with OCD and 22 normal volunteers. Visuospatial function and clinical symptom were assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Yale-Brown Obsessive Compulsive Scale, and the Maudsley Obsessive Compulsive Inventory. We found significant volume reductions in bilateral PPs, but there were no significant correlations between brain volumes and the ROCF copy score, immediate or delayed recall score, and clinical symptom in patients with OCD. These results suggest that volume reduction of the anterior STG, especially the PP, may be related to the pathophysiology of OCD, but further research may be needed to explore a relationship of the PP volume change with cognitive impairment observed in patients with OCD.

Adult↗