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PubMed2000

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↗
PubMed2000

Ventricular enlargement in schizophrenia spectrum patients with prodromal symptoms of obsessive-compulsive disorder.

We hypothesized that male patients with schizophrenia spectrum disorders who have prodromal symptoms of obsessive-compulsive disorder (OCD) have ventricular enlargement compared with non-psychotic OCD patients, and that the difference in the ventricular size would offer a clue to the early detection of schizophrenia spectrum disorders. The ventricle-brain ratios (VBRs) in eight male patients with schizophrenia or schizotypal personality disorder (SPD) who had prodromal symptoms of OCD were compared with eight male patients with non-psychotic OCD and 14 normal male comparison subjects using three-dimensional magnetic resonance imaging (MRI). The VBR of the schizophrenia spectrum group was significantly larger than those of the OCD group or comparison subjects. Even the minimum VBR in the schizophrenia spectrum group was larger than the maximum VBR in the OCD group. These results may suggest the usefulness of three-dimensional MRI for early detection of patients with schizophrenia spectrum disorders who manifest OCD symptoms early in the course of the illness.

Adolescent↗
PubMed2003

Neuropsychological correlates of P300 abnormalities in patients with schizophrenia and obsessive-compulsive disorder.

The cognitive significance of P300 abnormalities in schizophrenia and obsessive-compulsive disorder (OCD) was investigated. P300 was measured by an auditory oddball paradigm, in which a series of standard tones (1000 Hz) and target tones (1500 Hz) were presented. The subject's task was to count the number of the presented target tones. Cognitive functions were evaluated by neuropsychological tests, which were chosen to be sensitive to frontal and temporal dysfunction. Twenty-two schizophrenic patients, 19 OCD patients and 21 healthy controls participated. Event-related potentials measured at 15 electrode sites, which consisted of five levels on the left-right dimension and three levels on the anterior-posterior dimension, were included in the statistical analysis. P300 amplitudes on all 15 electrode sites were significantly smaller in schizophrenic and OCD patients than in the controls. Schizophrenic patients performed poorly on almost all neuropsychological tests, while OCD patients showed impaired performance on the Rey-Osterrieth Complex Figure Test and on a controlled oral word association test. In schizophrenic patients, P300 amplitude was associated with performance on verbal memory and learning by the Luria-Nebraska Neuropsychological Battery, while for OCD patients, P300 amplitude was related to the Trail Making Test, Part B response time. These results indicate that schizophrenic patients have generalized cognitive impairments, which are substrated by a wide range of cortical dysfunctions. The major cognitive deficits observed in OCD patients were impairments of controlled attention and self-guided, flexible behavior, which are mediated by the fronto-striatal system. The neurophysiological mechanisms underlying P300 abnormalities observed in schizophrenic and OCD patients are discussed.

Acoustic Stimulation↗
PubMed2006

Saccadic abnormalities in psychotropic-naive obsessive-compulsive disorder without co-morbidity.

BACKGROUND: Oculomotor studies have found saccadic abnormalities in obsessive-compulsive disorder (OCD), lending support for models postulating a central role for inhibition in OCD. Saccadic abnormalities in OCD may also be potential candidates for a biological marker, important for more endophenotype-oriented research. Saccadic abnormalities have not been examined in psychotropic-naive patients with OCD without co-morbidity. METHOD: We compared the error rates and latencies of 14 carefully selected adult psychotropic-naive patients with OCD with no co-morbid diagnosis and 14 pairwise matched healthy controls on a fixation task, on a prosaccade task and on an antisaccade task. RESULTS: Patients with OCD showed normal error rates on all tasks, but latencies on the antisaccade task were significantly increased. CONCLUSIONS: Our results indicate that patients with OCD have no gross impairment of oculomotor inhibitory capacities, but may have a disturbed capacity to deliberately initiate a saccade to an imagined target.

Adult↗
PubMed2004

Patterns of neural response to emotive stimuli distinguish the different symptom dimensions of obsessive-compulsive disorder.

Despite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.

Adult↗
PubMed2005

Brain stimulation techniques in the treatment of obsessive-compulsive disorder: current and future directions.

Recent studies on the epidemiology of obsessive-compulsive disorder (OCD) estimate 50 million patients suffer from OCD worldwide, thus making it a global problem. The treatment of OCD has changed substantially over the last 2 decades following the introduction of selective serotonin reuptake inhibitors, which provide symptom improvement in approximately 60% of patients. However, some patients remain resistant to the standard pharmacologic and behavioral treatments. Although some treatment-resistant patients respond to pharmacologic augmentations, others do not, and there is evidence that some of the most severe cases benefit from treatment with neurosurgical interventions. Besides pharmacologic, behavioral, and neurosurgical approaches, different brain stimulation methods-transcranial magnetic stimulation, deep brain stimulation, and electroconvulsive therapy-have been investigated in treatment-resistant patients with OCD. However, available data about the use of these techniques in OCD treatment are quite limited in terms of sample size and study design, given the difficulty in conducting standard blinded trials for these procedures. In addition, none of the mentioned treatments have received Food and Drug Administration approval for the treatment of OCD. Nevertheless, promising findings regarding efficacy, tolerability, and non-invasiveness and/or reversibility of these techniques have increased interest in investigating their use in treatment-resistant OCD.

Deep Brain Stimulation↗
PubMed2005

Investigation of response inhibition in obsessive-compulsive disorder using the Hayling task.

This study investigates response inhibition deficits in obsessive-compulsive disorder (OCD) by using the Hayling task. Sixteen OCD washers, 16 OCD checkers, 16 social phobic patients and 16 nonanxious controls were asked to complete sentences with either the expected word (section A: "initiation") or an unrelated word (section B: "inhibition"). The groups did not differ in terms of section B minus section A latencies. However, OCD washers and checkers made significantly more errors (sentence-related responses) in section B than social phobic patients and controls. In the OCD patients, the frequency of these errors correlates with the total OCD severity score and the compulsion subscore, but not with the depression and anxiety scores. These findings suggest that OCD patients might present a specific deficit affecting the inhibition of a prepotent response.

Adult↗
PubMed2006

Everyday memory functioning in obsessive- compulsive disorder.

Memory performance in obsessive-compulsive disorder (OCD) is discussed as a pathogenetic risk factor for the emergence of OCD, particularly checking compulsions. At present, however, findings are mixed and little is known about memory performance in tasks relevant to everyday functioning in patients with OCD. For the present study, memory performance was assessed in 31 patients diagnosed with OCD and 33 healthy controls with the Rivermead Behavioural Memory Test (RBMT), which covers a wide range of verbal and nonverbal memory components as well as prospective memory. OCD patients performed comparably to healthy controls on the memory task for verbal, nonverbal, and prospective memory (p > .1). According to norm values, memory performance was unimpaired in most OCD patients. The present findings further challenge a broad account of the "memory deficit" hypothesis of OCD and compulsive checking, respectively.

Activities of Daily Living↗
PubMed2007

Neuropsychological profiles of patients with obsessive-compulsive disorder: early onset versus late onset.

In this study, we assess the neuropsychological profiles of both early and late symptom-onset obsessive-compulsive disorder (OCD) patients. The early and late-onset OCD patients are compared to the control group with a series of neuropsychological measurements. The late-onset OCD patients exhibited impaired performance on the immediate and the delayed recall conditions of the Rey-Osterrieth Complex Figure Test (RCFT) and the letter and category fluency of the Controlled Oral Word Association Test (COWA), compared to the normal controls and the early-onset OCD patients. The controls and early-onset OCD patients did not differ on any of the neuropsychological measurements taken in this study. These results suggest that different neurophysiological mechanisms are in play in early and late-onset OCD patients, and age of onset can serve as a potential marker for the subtyping of OCD.

Adult↗
PubMed2002

The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study.

Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.

Adult↗
PubMed2000

Strategic processing and episodic memory impairment in obsessive compulsive disorder.

There is evidence that nonverbal memory problems in obsessive compulsive disorder (OCD) are mediated by impaired strategic processing. Although many studies have found verbal memory to be normal in OCD, these studies did not use tests designed to stress organizational strategies. This study examined verbal and nonverbal memory performance in 33 OCD patients and 30 normal control participants with the Rey-Osterrieth Complex Figure Test and the California Verbal Learning Test. OCD patients were impaired on verbal and nonverbal measures of organizational strategy and free recall. Multiple regression modeling indicated that free recall problems in OCD were mediated by impaired organizational strategies used during learning trials. Therefore, verbal and nonverbal episodic memory deficits in OCD are affected by impaired strategic processing. Results are consistent with neurobiological models proposing frontal-striatal system dysfunction in OCD.

Adult↗
PubMed2006

Decision making and set shifting impairments are associated with distinct symptom dimensions in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The authors examined how specific OCD symptom dimensions were related to neuropsychological functions using multiple regression analyses. A total of 39 OCD patients and 40 controls completed the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994), which is a test of decision making, and the Wisconsin Card Sorting Test (R. K. Heaton, 1981), which is a test of set shifting. OCD patients and controls showed comparable decision making. However, patients with prominent hoarding symptoms showed impaired decision making on the IGT as well as reduced skin conductance responses. OCD patients had poorer set shifting abilities than controls, and symmetry/ordering symptoms were negatively associated with set shifting. These results help explain previous inconsistent findings in neuropsychological research in OCD and support recent neuroimaging data showing dissociable neural mechanisms involved in mediating the different OCD symptom dimensions.

Adolescent↗
PubMed1999

Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder.

Although modulation of symptoms of obsessive-compulsive disorder (OCD) by serotonergic agents is well established, it is unclear whether an abnormality in the central serotonergic system is involved in its etiology. The serotonin (5-HT) transporter (5-HTT), which is the key modulator of serotonergic neurotransmission, is the target for serotonin reuptake inhibiting drugs (SRIs) that are uniquely effective in the treatment of OCD. In this preliminary study we report an association of a functional polymorphism in the 5-HTT 5' regulatory-region and OCD. Seventy-five OCD Caucasian patients and 397 ethnically-matched individuals from a non-patient control group were genotyped for the 5-HTTLPR. Population-based association analysis revealed that patients with OCD were more likely to carry two copies of the long allele (l) as compared to controls (46.7% vs 32.3%: chi2 = 5.19, P = 0.023). This finding replicates a recent family-based study of this polymorphism in OCD, and thus indicates that the 5-HTTLPR may be associated with susceptibility to OCD.

Alleles↗
PubMed2002

A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry.

The tic disorder Tourette's Syndrome (TS) and obsessive-compulsive disorder (OCD) are comorbid behavioral disorders, suggesting a shared but still unknown neuronal basis. To 'circuit-test' such behaviors, we previously engineered transgenic mice expressing a neuropotentiating protein (cholera toxin A1 subunit) within a cortical-limbic subset of dopamine D1-receptor expressing (D1+) neurons known to trigger glutamatergic excitation of orbitofrontal, sensorimotor, limbic and efferent striatal circuits thought to be hyperactive or affected in OCD and TS. These mice exhibited OCD-like behaviors including generalized behavioral perseveration and compulsion-like leaping and grooming-associated pulling and biting of skin and hair. We now report that these OCD-like mice, like humans, also exhibit comorbid TS-like behaviors, including juvenile-onset tics; increased tic number, complexity and flurries; increased tic severity in males; voluntary tic suppression; and tic responsiveness to a non-cataleptic TS+OCD drug therapy (clonidine, 0.01 mg kg(-1)). These data suggest that hormonal gender differences, apart from the influence of genetic or autoimmune etiologic factors, may be sufficient to aggravate tic severity in human TS males compared to TS females. These data also proffer a precise neuronal basis for TS+OCD, wherein tics and primary compulsions or obsessions are evoked by hyperactivity of various cortical-limbic projection neurons' glutamatergic output to efferent targets like the striatum. The 'Cortical-limbic Glutamatergic Neuron' (CGN) neuronal circuit model merges formerly opposed neurotransmitter models of TS and OCD, and is consistent with new clinical reports of increased cortical hyperactivity, striatal glutamate and striatal inhibitory D2 receptors, and reduced striatal responsiveness, in these disorders.

Analgesics↗
PubMed2006

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Adult↗
PubMed1999

[The value of magnetic resonance imaging in the clinical course of osteochondrosis dissecans in the knee and ankle joints].

PURPOSE: Definition of the prognostic value of clinical and morphological findings in the mid-term follow-up of OCD of the femoral condyle and talus. Demonstration of the consolidation of OCD on MRI depending on different therapies. MATERIALS AND METHODS: 76 patients were examined before and at an average of 30 months after conservative or surgical therapy using T1 and T2 weighted SE and 3D-FISP sequences and contrast enhanced studies. Six clinical (age, gender, site, duration and severity of symptoms, therapy) and six morphological (size, signal intensity, fragmentation, contrast enhancement, condition of cartilage, staging) data were registered on first MRI and correlated with the degree of consolidation of OCD (partial and complete remission, no change and progression) on control MRI. RESULTS: Patients under 17 years showed partial or complete remissions in 73%, those of 17 years or older in 33%. Conservatively treated patients had a higher remission rate (54%) than those treated with different surgical techniques (drilling 50%, refixation 43%, abrasio 38%). Small OCDs had a higher remission rate than large lesions (63% vs. 33%). OCDs covered with intact cartilage healed better than lesions with chondral defects (61% vs. 26%). Contrast enhancing fragments had a better prognosis than non-enhancing lesions (100% vs. 40%). CONCLUSIONS: Prognosis of OCD can be better estimated when size of OCD, condition of cartilage and enhancement of contrast agent is graduated with MRI and patient age is registered. The consequences for therapy planning are great.

Ankle Joint↗
PubMed2001

[Personality disorders and psychiatric comorbidity in obsessive-compulsive disorder and anorexia nervosa].

The aim of this prospective longitudinal study was to examine the course of adolescent anorexia nervosa and obsessive-compulsive disorder (OCD) (fulfilling DSM-III-R criteria) to compare psychiatric comorbidity and personality disorders of both groups. Because anorexia nervosa patients are mainly female, we compared them only with female OCD patients. Ten years after discharge the whole sample (32 female patients; 100%) of a group of 39 (32 female; 7 male) anorexia nervosa patients could be reexamined personally. 25 (61%) female patients of a group of 116 patients (41 female; 75 male) with obsessive-compulsive disorder were also reexamined. The anorexia nervosa patients were interviewed using the Structured Interview for Anorexia and Bulimia nervosa (SIAB [39]) to assess eating disorder symptomatology. To examine comorbid psychiatric disorders we used the Composite International Diagnostic Interview, WHO [44] and SCID-II [45] for personality disorders. One fourth of the patients with anorexia nervosa (AN) and 20% of the patients with obsessive-compulsive disorder had a personality disorder according to DSM-III-R. Most of them were "Cluster C"-personality disorders (AN: 28%; OCD: 20%). In the group of the female OCD patients 8% schizoid, 4% schizotype and 12% paranoid personality disorders were observed. The most prevalent psychiatric disorders were anxiety (AN: 28%; OCD: 20%) and affective disorders (AN: 16%; OCD: 16%). Our results support the view that in the course of anorexia nervosa and in obsessive-compulsive disorder there is a high prevalence of psychiatric comorbidity and "Cluster C"-personality disorders according to DSM-III-R. These results might confirm a model of a high vulnerability of the serotonergic neurotransmitter system in patients with anorexia nervosa or OCD.

Adolescent↗
PubMed2005

[Employment of professional help by patients with obsessive-compulsive disorders].

BACKGROUND: Several studies have investigated the pathway to psychiatric care. There are no results available for OCD. METHODS: Therefore, 23 patients with OCD were recruited among individuals seeking treatment at our university hospital outpatient clinic for anxiety and obsessive-compulsive disorders. All patients underwent a semistructured interview aimed at investigating their individual pathways to psychiatric care, to their experiences in the health system and to the first appearances of the psychiatric disorder. RESULTS: Those affected often trivialize and normalize the first symptoms of OCD. Also, in many cases, family members of OCD-patients do not understand the first symptoms of OCD. Contrary to patients with depression and anxiety disorder, OCD-patients often choose psychiatrists as their first professional contact. DISCUSSION: The first symptoms of the disorder must be diagnosed at an early stage in order to provide the patients with the acknowledged therapy for OCD.

Adult↗