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PubMed2007

Electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder.

In this study, we have attempted to determine the electrophysiological correlates of behavioral response inhibition in patients with obsessive-compulsive disorder (OCD). To evaluate response inhibition ability, we have used the Go/NoGo task and measured N2 and P3 event-related potential (ERP) components. Both the OCD and control groups exhibited greater and more frontally distributed N2 and P3 amplitudes in the NoGo condition compared to what we observed in the Go condition. However, the patients with OCD also manifested reduced NoGo-N2 and Go-N2 amplitudes at the frontocentral electrode sites compared to the controls. In addition, the NoGo-N2 amplitudes were more posteriorly distributed in patients with OCD than in controls. The NoGo-N2 amplitudes and latencies measured at the central sites were also negatively correlated with the obsession score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The OCD and control groups were comparable with regard to Go-P3 and NoGo-P3 amplitude and latencies. Our findings suggest dysfunctions in frontal regions mediating response inhibition in OCD, consistent with the involvement of response inhibition in the pathophysiology of this disorder. In addition, NoGo-N2 seems to result in more accurate response inhibition measurements in patients with OCD than does NoGo-P3.

Adult↗
PubMed2007

Factor analysis of the Yale-Brown Obsessive Compulsive Scale in a family study of obsessive-compulsive disorder.

Our objective in this study was to determine whether symptoms of obsessive-compulsive disorder (OCD) cluster into groups that can usefully subclassify OCD. Psychiatrists or psychologists interviewed 221 subjects using the Lifetime Anxiety Version of the Schedule for Affective Disorders and Schizophrenia (SADS-LA) for the diagnosis of DSM-IV disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD symptoms. We analyzed 16 symptom categories from the Y-BOCS using exploratory factor analysis to identify latent symptom dimensions. The relationship between these symptom dimensions and clinical characteristics and familiality was investigated. A four-factor model emerged as the best classification of OCD symptoms in the Y-BOCS. These factors were labeled Pure Obsessions, Contamination, Symmetry/Order, and Hoarding. The contamination factor was least likely to be associated with other Axis I disorders. Whereas no significant relationship was found between the factor scores of probands and the presence of OCD in their first-degree relatives, the Symmetry/Order and Hoarding factors did breed true. Hoarding was found to predict poorer treatment response. A four-factor classification of OCD features best describes the symptom patterns of a sample of patients with OCD. There were specific clinical correlates for these factors, and significant intrafamilial sib-sib correlations were found for the Symmetry/Order and Hoarding factors.

Adult↗
PubMed2007

Lifetime comorbidity of obsessive-compulsive disorder with psychiatric disorders in a community sample.

Epidemiological research indicates that obsessive-compulsive disorder (OCD) still constitutes a major public health problem. To study the comorbidity of psychiatric disorders in OCD subjects in a non-Western community sample, 25,180 individuals were interviewed face-to-face at home according to DSM-IV for diagnosis of psychiatric disorders by 250 trained clinical psychologists. The subjects were predetermined with a randomized cluster sampling method among all families residing in Iran. From 444 individuals diagnosed as OCD, 157 (35.4%) developed at least one of the psychiatric disorders. The most common comorbid psychiatric disorders were major depressive disorder and simple phobia. Comorbidity of two or more additional psychiatric disorders in OCD individuals was rare. There was no difference between genders in the comorbidity of psychiatric disorders with OCD. Low comorbidity of psychiatric disorders with OCD shows that OCD tends to occur in isolated rather than as cluster problems in a clinical sample.

Adult↗
PubMed2004

Pharmacotherapy for obsessive-compulsive disorder.

Pharmacotherapeutic options for obsessive-compulsive disorder (OCD) have expanded over the past half-century since medications were first found to be effective for the treatment of OCD. Currently, the serotonin reuptake inhibitors (SRIs) represent the first-line pharmacotherapy for OCD. High dosages and long trials of the SRIs are needed for adequate treatment of OCD. The use of SRIs for the treatment of OCD is reviewed, then other pharmacotherapeutic treatment options, including SRI augmentation and alternative monotherapies, are discussed. The preponderance of data demonstrates that SRI augmentation with neuroleptics is efficacious for treatment-refractory OCD. There is substantially less evidence supporting other alternative strategies. Finally, neurosurgical and device-based approaches for treatment-refractory OCD are reviewed.

Antipsychotic Agents↗
PubMed1990

New pharmacologic approaches to obsessive compulsive disorder.

Although obsessive compulsive disorder (OCD) traditionally has been considered a treatment-refractory syndrome, rigorous treatment studies over the past decade have demonstrated that most OCD patients respond to specific behavioral or pharmacologic therapies. In terms of the pharmacologic treatment of OCD, a relatively small group of antidepressant drugs (clomipramine, fluvoxamine, and fluoxetine) have been demonstrated to be antiobsessional. Several related antidepressants (desipramine, nortriptyline) appear to be ineffective for OCD. Clinical response requires prolonged treatment (greater than 6 weeks) with antiobsessional drugs and efficacy is not limited to depressed OCD patients. The few drugs that have been demonstrated to be antiobsessional share a high potency for the blockade of serotonin reuptake, suggesting a serotonergic mechanism for antiobsessional drug action. This suggestion has been further strengthened by studies demonstrating a high correlation between clinical response and changes in serotonergic markers with clomipramine treatment. Moreover, a serotonin antagonist, metergoline, appears to partly reverse the improvement observed following chronic clomipramine treatment. Overall, only about 50% of OCD patients appear to respond in any given pharmacologic treatment trial. Adjunctive treatments, such as lithium or L-tryptophan, have been reported to help in some cases. In addition, the use of neuroleptics either alone or in combination with antiobsessional drugs may be useful for OCD patients with psychotic features or tics. Pharmacologic treatments should be considered only one element of the therapeutic approach to be integrated with behavioral techniques as well as psychosocial interventions for the relief of this very intriguing syndrome.

Behavior Therapy↗
PubMed2005

N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder.

RATIONALE: Dysfunction of glutamatergic neurotransmission has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD) and recent clinical reports suggest that some glutamate modulating agents are efficacious in the treatment of this disorder. N-acetylcysteine (NAC) is a readily available amino acid compound that is thought to attenuate glutamatergic neurotransmission. NAC may be useful in treating psychiatric disorders involving glutamatergic dysfunction such as OCD. OBJECTIVES: To examine the efficacy of augmentation with NAC in a patient with serotonin reuptake inhibitor (SRI)-refractory OCD. METHODS: A patient with SRI-refractory OCD was treated with an off-label use of NAC augmentation of fluvoxamine over several weeks. RESULTS: NAC augmentation of fluvoxamine resulted in a marked decrease in Yale-Brown Obsessive Compulsive Scale (Y-BBOCS) score and a clinically significant improvement in OCD symptoms. CONCLUSIONS: NAC augmentation was effective in treating SRI-refractory OCD in this single case. Further research is warranted to investigate the use of NAC and other glutamate modulating agents in the treatment of OCD.

Acetylcysteine↗
PubMed2005

Stage-I osteochondritis dissecans versus normal variants of ossification in the knee in children.

BACKGROUND: Juvenile osteochondritis dissecans (OCD) has a better prognosis than the adult type. OBJECTIVE: We postulated that the excellent prognosis of juvenile OCD could be explained, at least in part, by the erroneous diagnosis of some developmental variants of ossification as stage-I OCD. MATERIALS AND METHODS: Knee MRIs of 38 children, ages 7.5-17.7 years (mean and median age 13 years), were retrospectively reviewed to look for features that might separate normal variants of ossification from stage-I OCD. These included age, gender, site, configuration of the lesion, residual cartilaginous model and presence of edema. RESULTS: Twenty-three patients (32 condyles) had ossification defects with intact articular cartilage suggestive of stage-I lesions. No stage-II lesions were seen in the posterior femoral condyles. Accessory ossification centers were seen in 11/16 posterior condyles and 3/16 central condyles. Spiculation of existing ossification was seen in 12/16 posterior condylar lesions and 1/16 central condyles. There was a predominance of accessory ossifications and spiculations in the patients with 10% or greater residual cartilaginous model. No edema signal greater than diaphyseal red-marrow signal was seen in the posterior condyles. Clinical follow-up ranged from 0.5 to 38 months, with clinical improvement in 22 out of 23 patients. CONCLUSION: Inclusion of normal variants in the stage-I OCD category might explain, in part, the marked difference in published outcome between the juvenile and adult forms of OCD. Ossification defects in the posterior femoral condyles with intact overlying articular cartilage, accessory ossification centers, spiculation, residual cartilaginous model, and lack of bone-marrow edema are features of developmental variants rather than OCD.

Adolescent↗
PubMed2004

Postpartum onset obsessive-compulsive disorder: diagnosis and management.

The postpartum period is associated with an increased risk of developing obsessive-compulsive disorder (OCD) in women. Postpartum onset OCD is often undiagnosed and untreated resulting in serious consequences for the patient, her family and the newborn. The symptoms of postpartum onset OCD may consist of obsessional intrusive thoughts about harming the newborn without compulsions or with both obsessions and compulsions. In this review, the phenomenology of postpartum onset OCD is described as well as strategies for screening and diagnosis. The review also characterizes the differences between postpartum onset OCD and postpartum depression and postpartum psychosis and explores strategies for managing postpartum onset OCD patients. Issues regarding pharmacologic treatment of OCD in breastfeeding mothers are also reviewed.

Breast Feeding↗
PubMed2006

Equivalent current dipole of word repetition effects in patients with obsessive-compulsive disorder.

We investigated cortical source localization of word repetition effects in patients with obsessive-compulsive disorder (OCD) by employing the equivalent current dipole (ECD) model with high-density 128 channels EEG and individual MRI as a realistic head model. Twelve OCD patients and 13 healthy control subjects performed a word/nonword discrimination task, in which the words and nonwords were visually presented, and some of the words appeared twice with a lag of one or five items. During the 200-500 ms post-stimulus period, the control group showed more positivity in the ERPs elicited by old words than in those elicited by new words, whereas the OCD patients did not. Furthermore, the OCD patients showed prolonged response times to the old words, as compared to the controls. We calculated the location and the power of the ECD sources at approximately 400 ms post-stimulus with the peak mean global field potentials. In both groups, the sources of word repetition effects were determined to be located in the inferior frontal gyrus. The right ECD powers of the ERP generators elicited by the new words were significantly higher in the OCD patients than in the control subjects. The OCD patients also exhibited significant alterations in the hemispheric asymmetry of ECD power during the processing of new words. These results suggest that OCD patients suffer from the encoding deficits in word processing, particularly in the left hemisphere.

Adult↗
PubMed1990

Endogenous event-related potentials in obsessive-compulsive disorder.

Brain event-related potentials (ERPs) were used to investigate central nervous system (CNS) correlates of cognitive function in obsessive-compulsive disorder (OCD). ERPs of 10 unmedicated OCD patients and 10 normal controls were measured in an auditory "oddball" task. Increasing task difficulty resulted in longer N200 and P300 latencies in normal subjects, but not in OCD patients. Moreover, OCD patients displayed shorter P300 latency than normal controls for the more difficult discrimination conditions. This replicates prior findings of Beech et al. (1983) for a visual task. For both levels of task difficulty, OCD patients also showed greater negativity than normal controls in the N200 region, which extended into the subsequent slow wave region. Negativities in the N200 and slow wave regions were larger at sites over the left hemisphere than the right hemisphere. The enhanced negativities and reduced P300 latency in OCD patients are discussed in terms of current theories postulating cortical hyperarousal and left hemisphere involvement in OCD.

Adolescent↗
PubMed1992

Fenfluramine stimulation of prolactin in obsessive-compulsive disorder.

The success of serotonergic reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) has suggested that serotonergic neurotransmission may play a role in the pathogenisis of this disorder. Prolactin responses to a 60-mg oral dose of fenfluramine in 26 medication-free patients with a DSM-III-R diagnosis of OCD were compared with those of 20 controls subjects. Fenfluramine produced a significant elevation of prolactin levels in both OCD patients and controls. Prolactin responses were significantly blunted in OCD patients compared with responses in control subjects. Female subjects in both groups showed greater prolactin responses to fenfluramine than did their male counterparts. There was a significant interaction between sex and the presence of OCD such that female patients had lower prolactin responses than their controls, while the difference between male patients and controls was not significant. Prolactin responses were not correlated with age, weight, drug level, depression, anxiety, or degree of OCD symptoms. The results are consistent with a relative reduction in serotonergic efficacy in the setting of OCD.

Adult↗
PubMed1995

Wisconsin Card Sorting Test performance in obsessive-compulsive disorder: no evidence for involvement of dorsolateral prefrontal cortex.

Wisconsin Card Sorting Test (WCST) performances were studied in 33 patients with obsessive-compulsive disorder (OCD) and 33 age-, sex-, and education-matched normal comparison subjects; the OCD patients were divided into four subgroups on the basis of their symptomatology. Neither the two groups of subjects nor the four OCD subgroups differed on any of the WCST neuropsychological indices. No relationship was demonstrated between test performance and clinical-epidemiological characteristics of the OCD patients. All of the OCD patients were being treated with fluvoxamine maleate, which improves OCD symptoms and could also improve WCST performances. Nevertheless, no remarkable differences in the WCST indices were observed in patients treated with fluvoxamine when compared with patients who had not received a specific therapy for at least 3 weeks. Since the WCST is widely considered sensitive to dysfunction of the dorsolateral prefrontal cortex, our results do not support the involvement of that brain region in OCD.

Anti-Anxiety Agents↗
PubMed1996

Autonomic activity in children and adolescents with obsessive-compulsive disorder.

Electrodermal activity and heart rate were recorded from 55 children and adolescents with obsessive-compulsive disorder (OCD) and 58 normal subjects in a protocol that included rest and mild stress periods, and nonsignal and signal stimuli, to determine if autonomic activity might be involved in the pathogenesis of OCD or might be related to important clinical differences. Few differences were observed between OCD and normal subjects despite adequate power to detect small differences due to the large number of subjects. Thus, autonomic activity appears not to be an important etiological factor in childhood OCD. However, electrodermal activity showed consistent positive correlations with ratings of the severity of OCD symptoms (but not with anxiety or depression ratings), suggesting that severely afflicted cases are autonomically sensitive to OCD-related stimuli or, conversely, that low electrodermal activity may be protective of symptom severity. Patients with a coexisting tic disorder (not Tourette's syndrome) had larger electrodermal responses to a novel stimulus and higher heart rate variability than those without tics but did not differ from normal subjects. These few differences seem insufficient to support the hypothesis of a separate etiology of OCD cases with a coexisting tic disorder.

Adolescent↗
PubMed1993

Quantitative electroencephalographic subtyping of obsessive-compulsive disorder.

Current neuropsychological, electrophysiological, and other imaging data strongly suggest the existence of a neurobiological basis for obsessive-compulsive disorder (OCD), which was long considered to be exclusively of psychogenic origin. The positive response of some OCD patients to neurosurgery, as well as the efficacy of agents that selectively block serotonin reuptake, lends further support to a biological involvement. However, a survey of the treatment literature reveals that only 45-62% of OCD patients improve with these specific medications. In a pilot study using a quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, we previously reported the existence of two subtypes of OCD patients within a clinically homogeneous group of patients who met DSM-III-R criteria for OCD. Following pharmacological treatment, a clear relationship was found between treatment response and neurometric cluster membership. In this study, we have expanded the OCD population, adding patients from a second site, and have replicated the existence of two clusters of patients in an enlarged, statistically more robust population. Cluster 1 was characterized by excess relative power in theta, especially in the frontal and frontotemporal regions; cluster 2 was characterized by increased relative power in alpha. Further, 80.0% of the members of cluster 1 were found to be nonresponders to drug treatment, while 82.4% of the members of cluster 2 were found to be treatment responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Surgical fixation of massive osteochondritis dissecans lesion using cylindrical osteochondral plugs.

Abstract The prognosis of osteochondritis dissecans (OCD) depends on the age of manifestation and the size of the lesion. Before epiphyseal closure, OCD usually responds well to the restriction of the patient's sporting activities. Surgical intervention is not always necessary. However, if the disease manifests after epiphyseal closure, it often needs surgical treatment because the lesion is usually found at an advanced stage (International Cartilage Repair Society [ICR] OCD II or more). Furthermore, if a massive lesion develops to separation (ICR OCD II or III) or displaced loose bodies (ICR OCD IV), despite restriction of sporting activities, the prognosis is poor. This report discusses 2 cases of OCD. One patient had a massive stage ICR I lesion, although the disease was found before epiphyseal closure. In the other patient, a 22-year-old man, a large separated fragment (ICR OCD IV) was found after epiphyseal closure. The separated surfaces of the fragment and the mother bed had become sclerotic. Cylindrical osteochondral grafts using jigs for Mosaicplasty (Smith & Nephew, Andover, MA) were performed on the 2 patients, both of whom made successful recoveries. These cases suggest that cylindrical osteochondral grafting is a useful procedure for difficult cases of large lesion size or late manifestation.

Adult↗
PubMed2005

Local-global processing in obsessive-compulsive disorder and comorbid Tourette's syndrome.

Neuropsychological and neuroimaging studies implicate attentional difficulties in obsessive-compulsive disorder (OCD), but results are inconsistent due possibly to sample heterogeneity and lack of control of comorbid disorders, such as Tourette's syndrome (TS). Nevertheless, it has been suggested that OCD symptomatology may be a result of over-focused attention at a local level. Therefore, this study aimed to examine the ability of OCD patients (pure and comorbid OCD + TS) to process local and global stimuli. Using a local-global paradigm, participants were required to respond to the directed level (local or global) of various stimuli. Results indicate that pure OCD participants were impaired on the global task, whereas comorbid OCD + TS participants had difficulty processing local information. Results are consistent with previously reported lateralisation anomalies and suggest that OCD negatively affects the ability to process hierarchically presented stimuli.

Adult↗
PubMed2005

Hypofunctioning of sensory gating mechanisms in patients with obsessive-compulsive disorder.

BACKGROUND: In obsessive-compulsive disorder (OCD) patients, functional abnormalities in basal ganglia/precentral circuitries cause cortical hyperexcitability and lack of inhibitory control. These loops can be partly explored by median-nerve somatosensory evoked potentials (SEPs), which functionally reflect the brain responsiveness to somatosensory stimuli. In healthy humans, SEPs' amplitude during voluntary finger movements is lower than during muscular relaxation (i.e., sensory gating). Cortical hyperexcitability in OCD could be eventually responsible for a reduction of sensory gating. This might have pathophysiologic implications for motor compulsions. METHODS: Median-nerve SEPs were recorded in 11 OCD patients and 9 healthy volunteers during muscle relaxation ("Relax") or finger movements of the stimulated hand ("Move"). Latencies and amplitudes of pre- and postcentral SEP components were compared between groups during "Relax" and "Move" conditions. RESULTS: In OCD patients, the responsiveness to sensory stimuli was enhanced for precentral SEPs. Sensory gating ("Relax" vs. "Move") in control subjects involved both pre- and postcentral SEPs, the former being reduced in amplitude by approximately 60%. In OCD patients, sensory gating was spatially restricted to precentral SEP components and was significantly reduced compared with control subjects (approximately 30%). CONCLUSIONS: Enhanced precentral SEPs and hypofunctioning of centrifugal sensory gating in OCD might reflect the inability to modulate sensory information due to a "tonic" high level of cortical excitability of motor and related areas, likely resulting from basal ganglia dysfunction. This might offer new insights into the pathophysiology of OCD.

Adult↗
PubMed2004

Amygdala responses to human faces in obsessive-compulsive disorder.

BACKGROUND: To assess the amygdala response to emotional faces in obsessive-compulsive disorder (OCD) using functional magnetic resonance imaging (fMRI). METHODS: Ten subjects with current OCD and 10 healthy control subjects underwent fMRI, during which they viewed pictures of fearful, happy, and neutral human faces, as well as a fixation cross. RESULTS: Across both groups, there was significant activation in left and right amygdala for the fearful versus neutral faces contrast. Data extracted from these functionally defined regions of interest indicated that OCD subjects exhibited a weaker response than control subjects bilaterally across all face conditions versus fixation. No group-by-face condition interactions were observed. CONCLUSIONS: Contrary to findings in other anxiety disorders, there was no observed increase in amygdala responsivity to fearful versus neutral human faces in OCD as compared with healthy control subjects. Moreover, across all face conditions, amygdala responsivity was attenuated in OCD subjects relative to control subjects. Therefore, the present findings are consistent with abnormal amygdala function in OCD and are of a character that may distinguish OCD from other anxiety disorders.

Adult↗