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Symptom subtypes of obsessive-compulsive disorder and their relation to dissociation.

We examined relations between obsessive-compulsive disorder (OCD) symptoms and dissociation in three studies. Studies 1 and 2 established a strong level of convergence between our two OCD symptom measures. Specific types of symptoms showed a clear convergent/discriminant pattern, indicating that they can be meaningfully distinguished from one another. In both studies, dissociation correlated more strongly with checking and obsessive intrusions than with cleaning, ordering, and hoarding. Moreover, these associations remained substantial even after controlling for neuroticism (Study 1) and other types of anxiety (Study 2). In Study 3, we replicated our key findings in a psychiatric outpatient sample, indicating that they are generalizable to clinical participants. Taken together, our results (a) establish a strong link between dissociation and OCD, and (b) illustrate the importance of analyzing different types of OCD symptoms separately.

Adult↗

Family distress and involvement in relatives of obsessive-compulsive disorder patients.

Obsessive compulsive disorder (OCD) affects the lives of patients as well as their relatives. Calvocoressi et al. (1995) suggested that accommodation (e.g., participating in the patient's rituals) by relatives of patients with OCD was related to global family dysfunction and distress. These investigators did not, however, examine the relationship between family accommodation and severity of the patients' OCD symptoms. In the present study we examined the relationship between families' reactions to the patient's illness (e.g., assistance with rituals, modification of family routine, rejection of the patient, etc.) and the patient's Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and Hamilton Depression scale ratings. We also examined the effects of family accommodation and rejection on treatment outcome. Results revealed that family distress, accommodation, and rejection were related to depression and anxiety in the family members, but not to severity of the patients' OCD. At posttreatment, family accommodation and modification of routine was related to the severity of patients' OCD. These results remained significant when the effect of pretreatment OCD severity was partialled out.

Adolescent↗

Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study.

The purpose of this study was to identify neuroimaging predictors of medication response in contamination-related obsessive compulsive disorder (OCD). Prior studies of OCD had indicated that glucose metabolic rates within orbitofrontal cortex (OFC) were inversely correlated with subsequent response to serotonergic reuptake inhibitors (SRIs) and that glucose metabolic rates within posterior cingulate cortex (PCC) were positively correlated with subsequent response to cingulotomy. Nine subjects with contamination-related OCD underwent a 12-week open trial of treatment with the SRI fluvoxamine. Percent change in Yale-Brown Obsessive Compulsive Scale score, from pre- to post-treatment, served as the index of treatment response. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) were obtained prior to treatment, in the context of a symptom provocation paradigm. Statistical parametric mapping was used to identify brain loci where pre-treatment rCBF was significantly correlated with subsequent treatment response. Consistent with a priori hypotheses, lower rCBF values in OFC and higher rCBF values in PCC predicted better treatment response. This same pattern of associations was present regardless of whether the imaging data were acquired during a provoked or neutral state. These findings are consistent with prior studies of OCD, indicating that PET indices of brain activity within OFC are inversely correlated with subsequent response to SRIs. In addition, similar to findings regarding cingulotomy for OCD, indices of activity within PCC appear to be positively correlated with response to fluvoxamine as well. Finally, this pattern is sufficiently robust as to be relatively independent of symptomatic state at the time of tracer uptake.

Adolescent↗

Incidence of obsessive-compulsive phenomena in the course of acute schizophrenia and schizoaffective disorder.

Studies examining OC phenomena in schizophrenic and schizoaffective disorders have shown a prevalence of such phenomena in 1 to 60% of schizophrenic or schizoaffective patients. In this prospective study, about 10% of 150 male patients suffering from acute psychotic disorders (fulfilling DSM-IV criteria for Schizophrenia or Schizoaffective Disorder) were found to have OC symptoms. These symptoms showed no correlation to the type and severity of psychosis. As only 19% of the patients with obsessions and compulsions during acute psychosis showed an obsessive-compulsive personality disorder prior to their psychotic episodes, it may be concluded that there is no clear linkage between intrapsychotic OC phenomena and premorbid anancastic personality traits.

Acute Disease↗

T102C and -1438 G/A polymorphisms of the 5-HT2A receptor gene in Turkish patients with obsessive-compulsive disorder.

OBJECTIVE: This study aimed to investigate the possible association between T102C and -1438 G/A polymorphism in the 5-HT2A receptor gene and susceptibility to and clinical features of obsessive-compulsive disorder (OCD). METHOD: Fifty-eight patients with OCD and 83 healthy controls were included in the study. All patients were interviewed and rated by Yale-Brown Obsessive-Compulsive Scale. T102C and -1438 G/A polymorphisms of 5-HT2A receptor gene were determined by PCR technique in DNAs of peripheral leucocytes. RESULTS: OCD patients and healthy controls did not show significant differences in genotype distribution for both polymorphisms investigated. We found that frequencies of the TT genotype for T102C polymorphism and the AA genotype for -1438 G/A polymorphism were significantly higher in patients with severe OCD compared to those with moderate or moderate-severe OCD. CONCLUSION: The -1438 G/A and T102C polymorphisms of the 5-HT2A receptor gene are not associated with an increased risk of OCD. Our data suggest that the TT genotype of T102C and the AA genotype of -1438 G/A polymorphism might be a factor in clinical severity of OCD.

Adolescent↗

Gender-related clinical differences in obsessive-compulsive disorder.

The purpose of the present study was to investigate the gender-related differences of clinical features in a sample of obsessive-compulsive (OCD) patients. One hundred and sixty outpatients with a principal diagnosis of obsessive-compulsive disorder (DSM-IV, Y-BOCS = 16) were admitted. Patients were evaluated with a semi-structured interview covering the following areas: socio-demographic data, Axis I diagnoses (DSM-IV), OCD clinical features (age at onset of OC symptoms and disorder, type of onset, life events and type of course). For statistical analysis the sample was subdivided in two groups according to gender. We found an earlier age at onset of OC symptoms and disorder in males; an insidious onset and a chronic course of illness were also observed in that group of patients. Females more frequently showed an acute onset of OCD and an episodic course of illness; they also reported more frequently a stressful event in the year preceding OCD onset. A history of anxiety disorders with onset preceding OCD and hypomanic episodes occurring after OCD onset was significantly more common among males, while females showed more frequently a history of eating disorders. We found three gender-related features of OCD: males show an earlier age at onset with a lower impact of precipitant events in triggering the disorder; OCD seems to occur in a relative high proportion of males who already have phobias and/or tic disorders; and a surfeit of chronic course of the illness in males in comparison with females.

Adult↗

Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD: Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS: Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS: The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

Adolescent↗

Gender in obsessive-compulsive disorder: clinical and genetic findings.

BACKGROUND: There is increasing recognition that obsessive-compulsive disorder (OCD) is not a homogeneous entity. It has been suggested that gender may contribute to the clinical and biological heterogeneity of OCD. METHODS: Two hundred and twenty patients (n=220; 107 male, 113 female) with DSM-IV OCD (age: 36.40+/-13.46) underwent structured interviews. A subset of Caucasian subjects (n=178), including subjects from the genetically homogeneous Afrikaner population (n=81), and of matched control subjects (n=161), was genotyped for polymorphisms in genes involved in monoamine function. Clinical and genetic data were statistically analyzed across gender. RESULTS: Compared with females, males with OCD (1) had an earlier age of onset, and a trend toward having more tics and worse outcome, (2) had somewhat differing patterns of OCD symptomatology and axis I comorbidity, and (3) in the Caucasian group, were more likely to have the high activity T allele of the EcoRV variant of the monoamine oxidase A (MAO-A) gene compared to controls, and (4) in the Afrikaner subgroup, were more frequently homozygous for the C allele at the G861C variant of the 5HT(1D beta) gene than controls. Females with OCD (1) reported more sexual abuse during childhood than males, (2) often noted changes in obsessive-compulsive symptoms in the premenstrual/menstrual period as well as during/shortly after pregnancy, and with menopause, and (3) in the Caucasian subgroup, were more frequently homozygous for the low activity C allele of the EcoRV variant of the MAO-A gene compared to controls, with this allele also more frequent in female patients than controls. CONCLUSION: This study supports the hypothesis that gender contributes to the clinical and biological heterogeneity of OCD. A sexually dimorphic pattern of genetic susceptibility to OCD may be present. Further work is, however, needed to delineate the mechanisms that are responsible for mediating the effects of gender.

Adolescent↗

A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission computed tomography (SPECT).

Several functional imaging studies have reported abnormalities of the orbitofrontal and anterior cingulate cortices, striatum and thalamus in obsessive-compulsive disorder (OCD). These studies have often been limited by small patient samples and image analysis methods that rely on region-of-interest (ROI) approaches. We have assessed resting regional cerebral blood flow with 99mTc-ECD SPECT in 26 unmedicated OCD patients and 22 healthy control subjects using the voxel-based Statistical Parametric Mapping method for data analysis. We found a significantly reduced ECD uptake in OCD patients relative to the control subjects in the right lateral orbitofrontal cortex, and in the left dorsal anterior cingulate cortex (P<0.001 two-tailed, uncorrected for multiple comparisons). There were significant positive correlations in the OCD group between the ECD uptake in the left lateral orbitofrontal cortex and ratings for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms. There were also unpredicted significant ECD uptake increases in the cerebellum in OCD patients, as well as a negative correlation between posterior cingulate ECD uptake and OCS severity (P<0.05, corrected for multiple testing). These results implicate specific subregions of the orbitofrontal and anterior cingulate cortices in the pathophysiology of OCD, as well as suggesting the involvement of other areas not usually included in ROI-based imaging studies. With the incorporation of voxel-based methods and the use of large patient samples, rCBF-SPECT studies may continue to provide valuable information about the functional anatomy of OCD.

Adult↗

Functional connectivity in depressive, obsessive-compulsive, and schizophrenic disorders: an explorative correlational analysis of regional cerebral metabolism.

In order to investigate the changes in functional relationships between brain regions in three psychiatric disorders, an exploratory statistical analysis of the regional cerebral metabolic rates for glucose (rCMRglu) obtained with positron emission tomography (PET) was performed. Correlations between various rCMRglu were computed in control, depressive, obsessive-compulsive, and schizophrenic groups to determine whether alterations of the correlation pattern were found in the psychiatric groups. The absence of correlation between left and right frontal lobes was common to the three psychiatric groups studied. Depressive patients recovered a better frontal interhemispheric coupling after successful treatment and the alterations in the depressed state also involved the relation between the right temporal cortex and the right thalamus. Obsessive-compulsive patients had not only lateral frontal dysfunction but also alterations in the functional relationships between cortex and thalami. In schizophrenic patients, the modifications of regional cerebral metabolic correlations involved both anterior and posterior cortical regions. Thus, although the relationship between left and right frontal lobes was altered in three psychiatric disorders, the pattern of functional connectivity between frontal regions, posterior cortical and subcortical regions differed depending on the diagnostic group.

Adult↗

FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder.

In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.

Adult↗

Obsessive-compulsive symptoms associated with clozapine and risperidone treatment: three case reports and review of the literature.

Treatment-emergent obsessive-compulsive symptoms (OCSs) have raised concern since the widespread introduction of serotonin-dopamine antagonists (SDAs) for the treatment of schizophrenia. Further investigations of SDA-emergent OCSs and their response to anti-obsessional agents will be beneficial for clinicians in helping patients who suffer from this problem. We present three cases of schizophrenia in which distressing OCSs occurred during clozapine or risperidone treatment. OCSs were assessed consecutively using the Yale-Brown Obsessive-Compulsive Scale. The OCSs of these three patients were responsive to anti-obsessional agents, including fluvoxamine, clomipramine, and paroxetine. We also review the current literature and discuss the possible pathophysiology and psychopathology of SDA-emergent OCSs.

Adult↗

Obsessive-compulsive disorder and schizophrenia in three identical twin pairs.

Three monozygotic twin pairs are described who are concordant for DSM-III-R obsessive-compulsive disorder while being discordant for schizophrenia or schizoaffective disorder. Follow-up interview showed the non-psychotic co-twins to have schizotypal personality disorder. It is concluded that obsessive-compulsive and schizophrenia-spectrum disorders can truly co-exist, thus supporting diagnostic changes introduced into DSM-III-R, and may in some cases be inherited together.

Adult↗

Strategy implementation in obsessive-compulsive disorder and trichotillomania.

BACKGROUND: The use of strategies to aid performance when undertaking neuropsychological tasks is dependent on intact fronto-striatal circuitry, and growing evidence suggests impaired spontaneous use of strategies in patients with obsessive-compulsive disorder (OCD). However, studies to date have not examined the effects of strategy training on task performance in OCD or in trichotillomania (compulsive hair-pulling, a condition that has been argued to share overlap with OCD in terms of phenomenology and co-morbidity). METHOD: The ability to generate novel visuospatial sequences using a computer interface was examined before and after undertaking optimal strategy training in 20 OCD patients, 17 trichotillomania patients, and 20 controls (matched for age, education, and IQ). RESULTS: OCD patients failed to improve ability to generate novel sequences above baseline despite successfully completing strategy training to the same extent as other groups. In contrast, performance of trichotillomania patients improved significantly after training to the same extent as controls. Groups did not differ on memory span, trial-by-trial action monitoring, or ability to generate novel visuospatial sequences prior to strategy training. CONCLUSIONS: Strategy implementation deficits, suggestive of cognitive inflexibility and fronto-striatal dysfunction, appear integral to the neurocognitive profile of OCD but not trichotillomania. Future research should investigate cognitive flexibility in obsessive-compulsive spectrum disorders using a variety of paradigms, and clarify the contribution of specific neural structures and transmitter systems to deficits reported.

Adult↗

HMPAO SPET does not distinguish obsessive-compulsive and tic syndromes in families multiply affected with Gilles de la Tourette's syndrome.

BACKGROUND: Gilles de la Tourette's syndrome (GTS) is a familial neuropsychiatric disorder characterized by tics and obsessive-compulsive behaviours (OCB). Previous HMPAO SPET studies of subjects with GTS have shown hypoperfusion of striatal and frontal areas. Studies of patients with primary obsessive-compulsive disorder have shown, in contrast, hyperperfusion of similar areas. METHODS: Twenty subjects from five families affected by GTS, including individuals with OCB but no tics, were examined using HMPAO SPET. RESULTS: There were abnormalities of regional cerebral perfusion in individuals with GTS, OCB and tics. Hypoperfusion was in striatal, frontal and temporal areas. There was no hyperperfusion. CONCLUSIONS: Regional cerebral blood flow patterns in individuals with OCB in families affected by GTS are comparable to their relatives with GTS and differ from individuals with primary OCD in the absence of a family history of tic disorders.

Adolescent↗

WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults.

What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

Adult↗

What is the optimal way to subdivide obsessive-compulsive disorder?

The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.

Cytogenetics↗

Quetiapine augmentation of selective serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a six-month follow-up case series.

Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as "much improved" on the Clinical Global Impression-Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction > or =35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.

Adult↗