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A brief motivational intervention for treatment-refusing OCD patients.

Cognitive behavioral therapy involving exposure and response prevention (ERP) is the psychosocial treatment of choice for obsessive-compulsive disorder (OCD). Despite this, ERP is not widely used by mental health practitioners, and so dissemination of ERP and other empirically supported treatment (ESTs) has become a priority. Even so, utilization of ESTs such as ERP remains below 50% even among therapists who self-identify as having a cognitive behavioral orientation. Barriers to the acceptance of ERP include practical obstacles such as lack of training and the cost of treatment, but also patient variables such as treatment refusal. It has been estimated that approximately 25% of OCD patients refuse ERP. This paper describes a brief, 4-session readiness intervention (RI) designed to decrease ERP refusal among patients with OCD. In this study, 12 patients with OCD who had refused ERP were randomized to RI or wait-list (WL). 86% of participants in the RI condition and 20% of participants in WL condition agreed to begin ERP following the 4-week period. ERP following RI, but not WL, was associated with a decrease in OCD symptoms comparable to that observed in OCD patients who did not refuse ERP. However, ERP following RI was associated with a high drop-out rate (50%), a figure that exceeds that typically seen in OCD treatment studies. Techniques to reduce drop-out as well as directions for future research are discussed.

Adult↗

Wisconsin Card Sorting Task (WCST) errors and cerebral blood flow in obsessive-compulsive disorder (OCD).

We compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive disorder (OCD) patients and 19 individually matched healthy controls. Measures of intelligence and mood were taken into account for all participants. Within the patient group, factors such as duration and severity of symptoms (as assessed using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored the relationship between OCD WCST errors and regional cerebral blood flow (rCBF) on brain dedicated, high resolution, single photon emission tomography (SPET). We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate rCBF, and regional values were quantified as ratios of cerebellar blood flow. WCST results confirmed OCD patients were significantly impared when compared with age- and sex-matched healthy volunteers. Patients made significantly more trials, more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive' subtotal significantly correlated with many WCST errors. Furthermore OCD WCST null-sorts correlated significantly with SPET OCD left inferior frontal cortical rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The implications of these findings are discussed in the context of other studies which examine functional imaging and neuropsychology in OCD.

Adult↗

Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD.

Different observations show a reduced functionality of the serotonin (5-HT) transporter in obsessive-compulsive disorder (OCD) that might be due to a disturbance of its regulation at intracellular level. Protein kinase C (PKC) has been reported to provoke a decrease in the number of the 5-HT transporter proteins. Therefore, we investigated whether OCD patients differed from control subjects in the effect of PKC upon the 5-HT transporter, after stimulation of this enzyme with 4beta-12-tetradecanoylphorbol 13-acetate (beta-TPA). Fifteen patients affected by OCD, according to DSM-IV criteria, were compared with a similar group of healthy subjects. The determination of 5-HT uptake was carried out according to the method of Arora and Meltzer with slight modifications. At baseline, OCD patients showed a significant decrease in the maximal velocity (V(max)) of 5-HT uptake, as compared with control subjects, with no change in the Michaelis-Menten constant (K(m)). The activation of PKC with beta-TPA provoked a significant decrease in V(max) values in both groups, but the effect was significantly more robust in OCD patients who, in turn, also showed also an increase in K(m) values. These findings could indicate the presence of hyperactivity of PKC in OCD that could be the result of increased activity of the phosphatidylinositol pathway. In addition, this suggests new potential therapeutic targets in OCD.

Adolescent↗

Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial.

CONTEXT: The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy. OBJECTIVE: To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD. DESIGN, SETTING, AND PARTICIPANTS: The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002. INTERVENTIONS: Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks. MAIN OUTCOME MEASURES: Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10. RESULTS: Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others. CONCLUSION: Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.

Adolescent↗

Cytogenetic analysis of obsessive-compulsive disorder (OCD): identification of a FRAXE fragile site.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disease characterized by recurrent obsessions, compulsions, or both. The prevalence rate of OCD is 2.1% in the general population. Here we report cytogenetic analysis of 26 patients affected with OCD. In one male patient (OCD-K33), we identified a fragile X chromosome by cytogenetic analysis with 21% of cells demonstrating a fragile site at Xq27-q28. Polymerase chain reaction (PCR) and Southern blot analysis demonstrated that the molecular basis of the OCD-K33 fragile X chromosome was expansion of the CCG repeat at FRAXE. The number of the expanded repeats was estimated to be more than 300 copies, qualifying it as a full FRAXE mutation. Further analysis of the family members of OCD-K33 revealed another member with a full FRAXE mutation (630-1,200 copies of the CCG repeat), who had the clinical phenotype of speech impairment, and two other members with normal phenotypes and no FRAXE expansion. The two FRAXE expansions lead to complete methylation at the CCG repeat. The co-segregation of the full FRAXE mutation with apparent neurologic disorders in the same family provides further support to the notion that FRAXE is a genetic neurologic condition. Our findings expand the spectrum of clinical phenotypes associated with FRAXE mutations.

Chromosomes, Human, X↗

Thought-action fusion and its relationship to schizotypy and OCD symptoms.

Thought-action fusion (TAF) is a cognitive bias that has been linked to obsessive-compulsive disorder (OCD). Preliminary evidence suggests schizotypal traits may be associated with some types of OCD obsessions but not others. We examined the relationship between each of the two major types of TAF (i.e., likelihood and moral), schizotypal traits, and OCD symptoms in 969 nonclinical undergraduate students. We hypothesized that likelihood TAF would be associated with schizotypal traits; whereas moral TAF would not. Consistent with prediction, schizotypal-magical thinking was significantly associated with likelihood TAF even after controlling for the effects of OCD symptoms, general anxiety, and depression. Moreover, the relationship between likelihood TAF and OCD symptoms was significantly attenuated after controlling for schizotypal traits. In contrast, moral TAF demonstrated negligible association with OCD symptoms, depression, or schizotypal traits. These findings provide preliminary support for the linkage between likelihood TAF and schizotypal traits.

Adolescent↗

Hoarding in obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, hoarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks; and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. Hoarding in relatives was associated with indecision in probands, independently of proband hoarding status. The findings suggest that hoarding behavior may help differentiate a distinct clinical subgroup of people with OCD and may aggregate in some OCD families. Indecision may be a risk factor for hoarding in these families.

Adolescent↗

Anxiety disorders and control related beliefs: the exemplar of Obsessive-Compulsive Disorder (OCD).

Beliefs about control have been postulated to be important to anxiety and mood disorders. In particular, the phenomenology of Obsessive-Compulsive Disorder (OCD) suggests that it may be an exemplar of an anxiety disorder where control issues related to the self (behavior and thoughts) and world (the external environment) are particularly important. However, only beliefs concerning the need to control thoughts have been incorporated into contemporary theories of OCD. This article summarizes the theoretical and empirical research relevant to control-related beliefs in OCD. It is suggested that discrepancies between an individual's desired level of control and their perceived level of control could contribute to OCD symptoms, and exacerbate the tendency for individuals with OCD to engage in magical ideation and superstitious rituals. Overall, this review demonstrates how consideration of control cognitions could enhance our understanding of OCD and further improve its treatment.

Anxiety Disorders↗

Empirical investigations of thought suppression in OCD.

Cognitive-behavioural models of obsessive-compulsive disorder (OCD) implicate thought suppression as a key factor in the development and persistence of the disorder. There is now more than a decade of research on thought suppression and its effects as they pertain to OCD. This paper briefly reports on initial thought suppression research and then offers a detailed review of recent thought suppression research that has directly examined the role of suppression in OCD. Theoretical and methodological issues in using thought suppression paradigms to understand OCD are discussed. It is concluded that this body of work continues to yield inconsistent findings with respect to the effects of suppression on thought frequency, although there are some consistent findings that suggest that suppression is driven by negative thought appraisal and is associated in turn with greater OCD symptomatology. Thus, there is support in this work for key tenets of cognitive-behavioural models of OCD. Suggestions for future research directions are offered.

Cognitive Behavioral Therapy↗

Obsessive-compulsive disorder: a 3-year prospective follow-up study of patients treated with serotonin reuptake inhibitors OCD follow-up study.

This study aimed to evaluate the long-term course of obsessive-compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM-IV criteria for OCD were followed prospectively for 3 years. Baseline information was collected on demographic and clinical characteristics, using standardized instruments. During the follow-up period, the clinical status of each patient was evaluated monthly in the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). The cumulative probability of achieving at least partial remission from obsessive-compulsive (OC) symptoms during the 3-year period was 65%. The probability of full remission was 38%. For subjects who achieved at least partial remission, the probability of subsequent relapse was 60%. Significant predictors of poor outcome included a longer duration of illness, a greater severity of OC symptoms at intake, and the presence of comorbid schizotypal personality disorder. The findings confirm that the course of illness in OCD is usually continuous with fluctuations in the intensity of OC symptoms. Despite adequate SRI therapy, relatively few patients achieve a completely asymptomatic state, and of those who achieve at least a partial remission, a substantial proportion subsequently relapse. One third of OCD patients is treatment-resistant. Further studies with large samples are required to adequately identify predictors of long-term outcome of OCD in order to optimize the choice among the existing treatment modalities. The development of alternative strategies is needed to improve the treatment approaches for treatment-resistant OCD patients.

Adolescent↗

The identification of OCD-related subgroups based on comorbidity.

BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) frequently have other psychiatric disorders. This study employed latent class analysis (LCA) to explore whether there are underlying clinical constructs that distinguish "OCD-related" subgroups. METHODS: The study included 450 subjects, case and control probands and their first-degree relatives, and LCA was used to derive empirically based subgroups of 10 disorders: OCD, obsessive-compulsive personality disorder (OCPD), recurrent major depressive disorder (RMDD), separation anxiety disorder, panic disorder or agoraphobia (PD/AG), tic disorders (TD), generalized anxiety disorder (GAD), somatoform disorders (hypochondriasis or body dysmorphic disorder), pathologic skin picking or nail biting (PSP/NB), and eating disorders (EDs). The derived classes were compared on several clinical variables. RESULTS: The best fitting model is a four-class structure: minimal disorder, predominant RMDD and GAD, "highly comorbid," and PD/AG and TD. The nature and number of disorders represented suggests that the first classes are distributed ordinarily on a dimension of severity, and the fourth class is qualitatively distinct. Support for this structure is based on the number of disorders, age at onset of OCD, neuroticism, and extraversion. CONCLUSIONS: In this OCD enriched sample, LCA identified four classes of disorder. These classes appear to conform to two subgroups that may prove useful in investigating the etiology of OCD.

Age of Onset↗

The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study.

OBJECTIVE: This study investigates the relationship of specific anxiety and affective disorders to obsessive-compulsive disorder (OCD) in a blind, controlled family study. METHOD: Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives of these probands, participated in the study. Subjects were examined by psychologists or psychiatrists using the Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials, and final diagnoses were made according to DSM-IV criteria, by consensus procedure. RESULTS: Except for bipolar disorder, all anxiety and affective disorders investigated were more frequent in case than control probands. Substance dependence disorders were not more frequent. Generalized anxiety disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD) and recurrent major depression were more common in case than control relatives. These disorders occurred more frequently if the relative was diagnosed with OCD. Only GAD and agoraphobia were more frequent in case relatives independent of OCD. CONCLUSION: GAD and agoraphobia share a common familial aetiology with OCD. The other anxiety and affective disorders, when comorbid with OCD, may emerge as a consequence of the OCD or as a more complex syndrome.

Adolescent↗

Neuropsychological performance of OCD patients before and after treatment with fluoxetine: evidence for persistent cognitive deficits.

BACKGROUND: There is an ongoing debate about the nature of executive dysfunction that accompanies obsessive-compulsive disorder (OCD). One reason for this may be that state-related factors, such as use of medication or co-morbid symptoms, confound with task performance. This study tried to isolate trait- from state-dependent cognitive impairments by examining variability of cognition following treatment. METHOD: Nineteen OCD patients were tested on the Cambridge Neuropsychological Test Automated Battery (CANTAB) before and after treatment with fluoxetine. Their pattern of performance was compared to the one observed in healthy volunteers (N = 24). RESULTS: OCD patients displayed impairments in planning ability, spatial memory and motor speed that persisted after clinical improvement. With treatment, OCD performance diverged from that of controls on measures of focused attention and strategic ability. However, these effects were rather mild as they did not entail a significant deterioration of performance within the OCD sample. CONCLUSIONS: Our data suggest that cognitive impairments in OCD are not secondary to symptoms and therefore form a trait feature of the disorder. The nature of the deficits refers to a chronic dysfunction of the dorsolateral-striatal circuit. The minor effects of treatment on task performance is in line with recent evidence that serotonin mediates cognitive functions of orbitofrontal cortex to a greater extent than those associated with dorsolateral prefrontal regions.

Adolescent↗

Glutamatergic dysfunction in OCD.

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (micromol/l) level was found to be significantly higher [F(1,31)=6.846, p=0.014] in OCD patients (47.12+/-4.25) compared to control subjects (41.36+/-3.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.

Adolescent↗

Microscopic localization of active gelatinases in equine osteochondritis dissecans (OCD) cartilage.

OBJECTIVE: To investigate the relationship between matrix metalloproteinase (MMP) activity and osteochondritis dissecans (OCD) in the equine joint. METHODS: Equine articular cartilage was obtained from normal (N = 8) and osteochondrotic (OCD) (N = 6) femoropatellar joints from horses at necropsy. The activity of gelatinase MMPs was determined in sections of cartilage by in situ gelatin zymography. RESULTS: Gelatinase activity was markedly increased in articular cartilage obtained from OCD samples and was particularly prominent in the deep cartilage zone. Activity was only seen in the pericellular area of chondrocytes. In addition, in OCD cartilage there were vertical lines of activity, starting from the deep zone and radiating towards the articular surface. In contrast, normal cartilage showed only a very small amount of gelatinolytic activity, which was not restricted to specific cartilage zones. Gelatin zymography of culture supernatants from isolated chondrocytes demonstrated increased production of MMP-2 and MMP-9 from OCD chondrocytes. CONCLUSIONS: Sections of articular cartilage from OCD lesions revealed MMP activity, especially in the deep zone adjacent to the calcified subchondral bone. This MMP activity could account for the loss of cartilage integrity in the deep cartilage zone and the vertical lines of activity could represent areas of mechanical weakness, likely to result in fissures and the release of cartilage fragments into the joint space.

Animals↗

Risperidone augmentation in the treatment of severe adolescent OCD in SSRI-refractory cases: a case-series.

BACKGROUND AND METHODS: The adverse effects and potential clinical value of risperidone as augmentation to selective serotonin reuptake inhibitor (SSRI) treatment in treatment resistant severe adolescent OCD patients were examined in 17 adolescents (15-19 years old, 8 males and 9 females) in an open label trial of risperidone 1-2 mg daily. RESULTS: After 12 weeks of augmenting treatment, statistically significant improvements were reflected in OCD symptom ratings (mean total Y-BOCS/CY-BOCS scores after treatment with second SSRI 24.2 +/- 2.6 versus 19.9 +/- 2.9, p < 0.001) and global assessment scores (mean CGAS, 69.4 +/- 11.4 versus 74.7 +/- 9.6, p < 0.001). Four patients had moderate improvement of more than 25% reduction in Y-BOCS scores in OCD symptoms. Further 10 patients had a reduction of 10-25% in total score, indicating slight improvement. One patient (6%) dropped from clinical OCD to a subclinical level of OCD (Y-BOCS total score < 15). No patient was found to have worsened during augmentation treatment. Eight cases had weight gain and sedation was reported in four cases. CONCLUSION: These preliminary findings suggest that augmentation with risperidone in dosages up to 2 mg daily might be efficient in adolescents with treatment resistant OCD.

Adolescent↗

Continuation treatment of OCD: double-blind and open-label experience with fluoxetine.

Recent advances in the pharmacotherapy of obsessive compulsive disorder (OCD) have led to a significant reduction in suffering and a return to productive living for many patients previously considered refractory to treatment. However, OCD can be a chronic disorder that significantly detracts from an individual's well-being. Potent inhibitors of 5-hydroxytryptamine (5-HT) reuptake have emerged as the first-line choice in the pharmacotherapy of OCD. These members of the therapeutic armamentarium for OCD, while associated with acute symptomatic improvement, have not been extensively studied during continuation therapy. In this study, 274 primary OCD subjects completed a 13-week, double-blind, placebo-controlled trial of three fixed doses of fluoxetine. Treatment responders (n = 76) continued their blinded treatment, whereas acute fixed-dose nonresponders began an open-label trial on their maximally tolerated dose (up to 80 mg daily) for 24 weeks. Responders maintained their acute treatment gains; in addition, all three doses of fluoxetine (20, 40, and 60 mg) were associated with further Y-BOCS improvement over the 24-week extension. Fluoxetine 60 mg achieved a statistically significantly greater reduction in Y-BOCS than placebo during the continuation. Open-label study subjects (n = 198) benefited from dose titration, with two thirds achieving a clinical response during the subsequent 24 weeks. Fluoxetine was well tolerated during both 24-week continuation periods. Only 4 (5.7%) of 70 subjects treated with fluoxetine in the responder extension terminated early due to an adverse event. The open-label extension, fluoxetine (to 80 mg), also demonstrated a low rate of adverse events; the profile of events was consistent with the extensive fluoxetine experience in other clinical populations. In conclusion, fluoxetine continuation treatment in OCD was associated with a maintained/improved symptomatic profile in most cases. Further dose titration improved the outcome of many acute, fixed-dose nonresponders. Continuation treatment with fluoxetine appeared to be well tolerated with few late-emergent adverse events.

Adolescent↗

Reduced serotonin transporter-availability in obsessive-compulsive disorder (OCD).

We investigated the availability of brain serotonin transporters in 10 drug-free patients with obsessive-compulsive disorder (OCD) and age-matched healthy controls in vivo using single-photon emission computed tomography (SPECT) and the radioligand [(123)I]-2beta-carbomethoxy-3beta-(4-idiophenyl)-tropane ([(123)I]beta-CIT). For quantification of regional serotonin transporter a ratio of specific to non-specific [(123)I]beta-CIT-binding was used. The availability of serotonin transporter was calculated using regions of interests (ROI) for thalamus/hypothalamus, midbrain, brainstem (highest density of serotonin transporter) and cerebellum as a reference. The mean specific to non-specific [(123)I]beta-CIT binding ratios in the thalamic/hypothalamic ROI were 4.95 +/- 0.57 (OCD patients), and 5.48 +/- 0.87 (control group). The mean ratios in the midbrain ROI were 3.51 +/- 0.45 (OCD patients) and 4.89 +/- 1.23 (controls) and in the brainstem ROI the ratios were 2.38 +/- 0.76 (OCD patients) and 3.53 +/- 1.01 (controls). This in vivo finding of significant reduced serotonin transporter availability in midbrain/brainstem using [(123)I] beta-CIT SPECT further supports the serotonin deficit hypothesis of OCD.

Adult↗