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Biomedical subjects

Harold J G M van Megen

Publications and source records attributed to Harold J G M van Megen.

16 recordsLinked to original sources
PubMed2006

Spatial working memory in obsessive-compulsive disorder improves with clinical response: A functional MRI study.

To date, only a few studies have examined whether executive dysfunctions in obsessive-compulsive disorder (OCD) are state or trait dependent and almost none of these studies have used functional neuroimaging techniques. We conducted a functional MRI study before and after 12 weeks of pharmacological treatment in 14 psychotropic-free patients with OCD without comorbidity. Subjects performed a spatial variant of a working memory task with four increasing levels of difficulty (n-back task). Responders and non-responders did not differ in clinical and demographical characteristics or brain activation patterns before treatment. Performance improved only in responders and was associated with a change in the overall pattern of brain activity during the task. We found no correlations between (changes in) scores on symptom scales, brain activity and performance. Our preliminary findings suggests that spatial working memory deficits in OCD and their functional anatomical correlates, as assessed with a spatial n-back task, are, at least to some extent, state dependent.

Adult↗
PubMed2005

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine.

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.

Adolescent↗
PubMed2005

Behavior therapy augments response of patients with obsessive-compulsive disorder responding to drug treatment.

OBJECTIVE: In many patients with obsessive-compulsive disorder (OCD), residual symptoms persist despite a clinically meaningful response. The objective of this study was to examine whether addition of behavior therapy would augment treatment outcome in these patients. METHOD: Ninety-six patients with DSM-IV OCD who had responded to 3 months of drug treatment were randomly assigned to either receive addition of behavior therapy or continue on drug treatment alone for 6 months. Patients who continued on drug treatment alone eventually received addition of behavior therapy for 6 months. Data were gathered from October 1998 to June 2002. RESULTS: OCD patients who received addition of behavior therapy showed a greater improvement in obsessive-compulsive symptoms (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score change = -3.9 in the completers sample) than those who continued on drug treatment alone (Y-BOCS score change = +3.9 for completers). Significantly more patients who received addition of behavior therapy were in remission compared with those who continued on drug treatment alone (p < .0001 for completers). Patients who received behavior therapy after 6 months of drug treatment alone showed a nonsignificant decline in obsessive-compulsive symptoms (Y-BOCS score change = -2.7 for completers); however, the remission rate found in this group was comparable to the remission rate found in the group of patients receiving addition of behavior therapy directly after responding to drug treatment. CONCLUSION: The results indicate that addition of behavior therapy is beneficial for patients who have responded to drug treatment. The data also suggest that the effect is greater when behavior therapy is added immediately after attainment of the drug response.

Adult↗
PubMed2004

Use of factor analysis to detect potential phenotypes in obsessive-compulsive disorder.

This study aimed to identify symptom dimensions in obsessive-compulsive disorder (OCD) in order to reveal distinct clinical phenotypes. Factor analysis of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist on item level was performed on data from 335 outpatients with primary OCD. The relationship of demographic and clinical characteristics to the resulting factor scores was examined. A principal component analysis identified the following five consistent symptom dimensions: (1) contamination and cleaning, (2) aggressive, sexual and religious obsessions, (3) somatic obsessions and checking, (4) symmetry and counting/arranging compulsions and (5) high-risk assessment and checking. We observed significant differences in sex distribution, age of onset, Y-BOCS scores and familial prevalence of OCD in relation to the symptom dimensions. These findings provide further evidence for distinct clinical phenotypes in OCD.

Adult↗
PubMed2004

Symptom dimensions in obsessive-compulsive disorder: factor analysis on a clinician-rated scale and a self-report measure.

Although obsessive-compulsive disorder (OCD) is regarded as a unitary nosological entity, it encompasses a rich variety of heterogeneous mental and behavioural phenomena. The identification of clinical subtypes within this broad concept has been a focus of attention in recent years. In the present study, we administered a clinician-rated scale, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with the Y-BOCS Symptom Checklist (Y-BOCS CL), as well as a self-report questionnaire, the Padua Inventory revised (PI-R), to 150 outpatients with OCD. A principal component analysis on the Y-BOCS CL, along with the PI-R, identified 6 consistent symptom clusters: (1) contamination obsessions and cleaning compulsions, (2) sexual/religious/somatic obsessions and checking, (3) high risk assessment and checking, (4) impulses and fear of loss of control, (5) need for symmetry and exactness, and ordering and counting compulsions, and finally (6) rumination. The Y-BOCS CL and PI-R showed great overlap and consistency regarding content and severity of the OCD symptoms. On inspection of items with identical content, only half of the items showed significant agreement. Both inventories have unique factors: rumination is represented solely in the PI-R, somatic obsessions and checking solely in the Y-BOCS CL. This means that the use of both clinician-administered and self-report measures is recommended, so that the entire spectrum of symptoms is represented.

Adult↗
PubMed2004

Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine in patients with panic disorder and controls.

Oral and intravenous challenge paradigms with the direct 5-HT agonist meta-chlorophenylpiperazine (m-CPP) in panic disorder (PD) have shown only moderate sensitivity or selectivity of the panicogenic effects in PD. However, the results of a study examining the effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in healthy volunteers suggested that this approach may be a more selective and sensitive panicogenic paradigm in PD. We therefore compared the behavioural, neuroendocrine and physiological effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in 10 patients with PD and 10 healthy controls. Panic attacks were significantly more provoked in patients with PD (90%) compared to healthy controls (0%). Effects on the behavioural, but not on the neuroendocrine and physiological parameters, were significantly greater in patients. Our data suggests that the behavioural effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in patients with PD indeed show a unique combination of high sensitivity and selectivity.

Adult↗
PubMed2004

Axis I and II comorbidity in a large sample of patients with obsessive-compulsive disorder.

BACKGROUND: No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms. OBJECTIVE: To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive-compulsive disorder (OCD). METHOD: 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics. RESULTS: Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder. LIMITATIONS: A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses. CONCLUSION: Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.

Adult↗
PubMed2004

Glutamate and anxiety.

Although glutamate is a simple molecule, its actions in the limbic system and areas concerning anxiety are complex and widespread. These actions are mediated through different combinations of ionotropic and metabotropic glutamate receptors. Preclinical studies have shown that compounds active at NMDA, AMPA/kaïnate and metabotropic receptors might have anxiolytic properties. The major research effort so far has been directed towards the development of compounds which modulate the function of NMDA receptors. In general, the utility of NMDA and AMPA/kaïnate antagonists is greatly hampered by adverse effects. For the treatment of clinical anxiety disorder a more delicate regulation of the glutaminergic system is required. It is encouraging that different ways to fine-tune the glutaminergic system are emerging, e.g., modulators of the glycine site and compounds acting at the AMPA receptor. Metabotropic glutamate receptor agonists and antagonists are in particular promising in this respect. It can be expected that selective modulators of glutamate activity will be of great clinical significance for the treatment of anxiety disorders.

Animals↗
PubMed2004

A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder.

BACKGROUND: The treatment guidelines for obsessive-compulsive disorder (OCD) propose to switch serotonin reuptake inhibitors (SRIs) in case of refractoriness. However, no controlled research has been published yet that prospectively examined the effects of changing SRIs. This article describes the first double-blind switch study of 2 SRIs in patients with OCD. METHOD: 150 patients with primary OCD, according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (N = 75) or 60 mg/day of paroxetine (N = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and nonresponse was defined as less than 25% reduction on the Y-BOCS. After a 4-week tapering phase, 43 nonresponders were switched to 12 additional weeks of the alternate antidepressant, of which 16 patients received venlafaxine and 27 received paroxetine. RESULTS: Eighteen of 43 patients benefited from a switch to the alternate SRI with a mean +/- SD decrease of at least 25% on the Y-BOCS. At the end of 12 weeks, responder rates were 56% for paroxetine (15/27) and 19% for venlafaxine (3/16). An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 1.8 +/- 3.5 in the venlafaxine group and 6.5 +/- 7.1 in the paroxetine group. After 2 consecutive SRI trials, 109 of 150 patients (73%) achieved a Y-BOCS decrease of at least 25%. CONCLUSION: The results of the current study show that 42% of the nonresponders benefited from a crossover to the other SRI, and that paroxetine was more efficacious than venlafaxine in the treatment of nonresponders to a previous SRI trial. Switching SRIs in case of refractoriness may be considered a useful strategy for patients with OCD.

Administration, Oral↗
PubMed2004

A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors.

BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD. METHOD: Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of "very much improved" or "much improved" and a decrease of > or = 35% in Y-BOCS score. RESULTS: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F=16.99, df=1,38; p <.001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi2=4.8, df=1, p=.028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness. CONCLUSION: The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone.

Adolescent↗
PubMed2003

Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex.

Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD.

Adult↗
PubMed2003

Effect of a pharmacological intervention on quality of life in patients with obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) not only suffer from obsessive-compulsive symptoms, but also the disorder is associated with aberrant social functioning and a diminished quality of life (QoL). Although studies concerning the effect of treatment interventions on symptoms are common, studies with regard to the effect of treatment interventions on QoL are scarce. We examined the effect of a pharmacological intervention on QoL in 150 patients with OCD. Furthermore, we studied whether two different drugs, venlafaxine and paroxetine, differed in their effect on QoL. Finally, we examined whether any found improvement in QoL was related to improvement in symptoms and/or the baseline self-directedness score, which is one of the character dimensions of the psychobiological model of Cloninger. We demonstrated that QoL, as assessed with the Lancashire Quality of Life Profile, improved following pharmacological intervention, for which paroxetine and venlafaxine appeared to be equally effective. Furthermore, neither improvement in symptoms, nor baseline self-directedness, was associated with the improvement in QoL.

Adult↗
PubMed2003

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder.

SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.

Adolescent↗
PubMed2003

Emerging skin-picking behaviour after serotonin reuptake inhibitor-treatment in patients with obsessive-compulsive disorder: possible mechanisms and implications for clinical care.

Pathological skin-picking is a self-injurious, impulsive behaviour with repetitive, and ritualistic characteristics. A number of studies show that selective serotonin reuptake inhibitors (SSRIs) may be efficacious in reducing skin-picking behaviour. Two case reports are presented demonstrating that SSRI-treatment may induce or aggravate pathological skin-picking behaviour. Possible mechanisms of SSRI-induced pathological skin-picking and implications for clinical care are discussed.

Adult↗
PubMed2003

Assessment of DSM-IV personality disorders in obsessive-compulsive disorder: comparison of clinical diagnosis, self-report questionnaire, and semi-structured interview.

In patients with obsessive-compulsive disorder, personality disorders are not many times assessed according to DSM-IV criteria. The purpose of the present study is to examine the prevalence of personality disorders diagnosed according to the DSM-IV in a severely disordered OCD population (n=65) with three different methods of assessing personality disorders (structured interview, questionnaire, and clinical diagnoses). Furthermore, correspondence between these different methods was investigated and their construct validity was examined by relating the three methods to external variables. Each method resulted in a predominance of Cluster C personality disorders, and obsessive-compulsive personality disorder had the highest prevalence. However, there was generally low correspondence regarding which patient had which personality disorder. Results concerning the relation of external variables were the most promising for the structured clinical interview.

Adult↗