PubMed Health⌕ Search

Biomedical subjects

Damiaan Denys

Publications and source records attributed to Damiaan Denys.

At least 19 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↗
PubMed2006

Philosophy, Ethics, and Humanities in Medicine: expanding the open-access conversation on health care.

Natural philosophy once spanned the fields of philosophy, science, and medicine. Scientific disciplines and medical specialties have rapidly achieved independence, and the availability of the internet and open-access publishing promises a further expansion of knowledge. Nevertheless, a consideration of the grounding concepts and ethical principles that underlie health care remains paramount. It is timely, therefore, to contribute to the global conversation on health care with an open-access journal that focuses on addressing the conceptual basis of medicine and related disciplines, considering the ethical aspects of clinical practice, and exploring its intersection with the humanities (including history of medicine).

Journal Article↗
PubMed2006

Association between serotonergic candidate genes and specific phenotypes of obsessive compulsive disorder.

BACKGROUND: The successful use of serotonin reuptake inhibitors (SRIs) in obsessive-compulsive disorder (OCD) has led to the hypothesis that serotonin plays a pivotal role in the pathogenesis of OCD. The purpose of the present study was to investigate the role of the serotonin transporter (5-HTT) and serotonin 5-HT1B and 5-HT2A receptor genes in OCD. METHOD: The distribution of polymorphic variants was analyzed in 156 OCD cases and 134 control individuals by means of case-control association studies. Potential relevant OCD phenotypes founded on age of onset, positive family history for OCD, clinical subtypes, comorbidity and symptom severity were stratified according to 5-HTT, 5-HT1B and 5-HT2A genotypes. RESULTS: Patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, taking in account OCD phenotypes, we found indication towards an association of the 5-HTTLPR S-allele with female OCD patients, and the 5-HT2A G-allele and GG genotype with patients with a positive family history of OCD and an early onset of disease. CONCLUSIONS: Our data yields interesting preliminary results as regards the genetic underpinnings of OCD phenotypes that warrant further discussion and investigation.

Adult↗
PubMed2006

Sexual pleasure in women with obsessive-compulsive disorder?

BACKGROUND: Although patients with OCD have reported sexual dissatisfaction frequently, controlled studies are sparse. This study compared subjective appreciation of sexuality and sexual functioning between OCD patients and healthy subjects and controlled for the influence of medication or OCD subtypes on sexual functioning and satisfaction. METHODS: Self-report questionnaires were sent to 350 female outpatients with OCD and 101 questionnaires were completed. RESULTS: OCD patients reported significantly more sexual disgust (t = 4.48, p < 0.001), less sexual desire (t = 5.52, p < 0.001), sexual arousal (t = 4.28, p < 0.001), and satisfying orgasms (t = 4.94, p < 0.001), than controls. Neither medication nor OCD phenotypes did affect outcome. LIMITATIONS: A self-report questionnaire and relatively low response-rate (29%) could have biased the results and the sample was limited to women so results might not be generalisable to men. CONCLUSIONS: Female patients with OCD report low sexual pleasure, high sexual disgust and diminished sexual functioning, which are not only attributed to medication or contamination obsessions. In the future, clinicians should explicitly ask for sexual function in the assessment of patients with OCD.

Adult↗
PubMed2006

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive-compulsive disorder in males.

BACKGROUND: Mounting evidence suggests the involvement of the dopamine system in the pathophysiology of obsessive-compulsive disorder. METHOD: The relationship of the dopamine D(2) receptor (DRD2) TaqI A, and catechol-O-methyl-transferase (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder (OCD) was examined in a sample of 150 patients and 150 controls. RESULTS: OCD patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, when the sample was stratified by gender, there was a trend to a significant predominance of the DRD2 A2A2 genotype (p=0.049), and a higher frequency of the DRD2 A2 allele (p=0.020) and low-activity COMT allele (p=0.035) in male OCD patients compared to male controls. In addition, we observed an association of the DRD2 A2A2 genotype in patients with an early onset of disease (<or=15 years) (p=0.033). CONCLUSIONS: Our findings replicate previous reports and provide support for a potential role of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

Adult↗
PubMed2006

Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders.

This article reviews new developments of pharmacotherapy in obsessive-compulsive disorder (OCD) and OC spectrum disorders of the past five years. New developments primarily involved the ex-tension of evidence of efficacy of serotonin reuptake inhibitors(SRIs), the use of atypical antipsychotics in addition to SRIs for treatment refractory patients, the combination of pharmacotherapy with behavior therapy, and studies assessing predictors of response. Today, frontline pharmacological treatment of OCD still consists of drugs with potent serotonin reuptake inhibition proper-ties. In case of non-response, treatment options comprise adding another drug, increasing the dose, switching drugs, or changing the mode of delivery.

Brain↗
PubMed2006

Female hormones affect symptom severity in obsessive-compulsive disorder.

There is circumstantial evidence that reproductive events can influence symptom severity of obsessive-compulsive disorder (OCD). We sent self-report questionnaires to 350 female outpatients with OCD to examine the relationship between the menstrual cycle, pregnancy, menopause, hormonal contraceptives, selective serotonin reuptake inhibitors and symptom severity of OCD. Yale-Brown Obsessive-Compulsive Scale scores were used at three serial time points during the menstrual cycle to assess symptom severity. One hundred and one out of 350 questionnaires (29%) were returned and completed. Forty-nine patients reported an exacerbation of OCD symptoms during the premenstrual period, nine during the menopause and 17 patients during pregnancy, whereas 11 patients mentioned improvement of OCD symptoms during pregnancy. Premenstrual dysphoric disorder could only partly explain a premenstrual exacerbation of OCD symptoms. Exacerbation of OCD could be related to reproductive events in a considerable number of patients, especially the premenstrum. Because reproductive cycle events influence the symptom severity of OCD, the menstrual cycle should be taken into account when assessing the severity of OCD symptoms during pharmacological studies.

Adult↗
PubMed2006

Adjunctive quetiapine for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: a meta-analysis of randomized controlled treatment trials.

Small studies have shown positive effects from adding a variety of antipsychotic agents in patients with obsessive-compulsive disorder who are unresponsive to treatment with serotonin reuptake inhibitors. The evidence, however, is contradictory. This paper reports a meta-analysis of existing double-blind randomized placebo-controlled studies looking at the addition of the second-generation antipsychotic quetiapine in such cases. Three studies fulfilled the inclusion criteria. Altogether 102 individuals were subjected to analysis using Review Manager (4.2.7). The results showed evidence of efficacy for adjunctive quetiapine (<400 mg/day) on the primary efficacy criterion, measured as changes from baseline in total Yale-Brown Obsessive Compulsive Scale scores (P=0.008), the clinical significance of which was limited by between-study heterogeneity. The mechanism underlying the effect may involve serotonin and/or dopamine neurotransmission.

Adult↗
PubMed2005

Effects of paroxetine and venlafaxine on immune parameters in patients with obsessive compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with an altered activity of the immune system. This study was carried out to investigate whether treatment with paroxetine and venlafaxine modifies the immune function in OCD and whether this modification is related to treatment outcome. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK-cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 42 outpatients with OCD who participated in a 12-week, double-blind SRI trial. RESULTS: Paroxetine and venlafaxine treatment did not affect immune parameters and clinical response was not directly related to altered activity of the immune system. Responders, defined as having a >or=25% decrease on the Y-BOCS, differed from non-responders with regard to the change of TNF-alpha values. CONCLUSIONS: The present results suggest that paroxetine and venlafaxine do not affect immune parameters and that clinical response is not related to altered activity of the immune system in OCD. Nonetheless, our data yielded interesting preliminary results that warrant further discussion and investigation.

Adult↗
PubMed2005

Predictors of pharmacotherapy response in anxiety disorders.

Although treatment with different compounds such as tricyclic antidepressants, selective serotonin reuptake inhibitors, high-potency benzodiazepines, and monoamine oxidase inhibitors has been proven effective in anxiety disorders, 20% to 40% of patients are nonresponders. Given the limited efficacy, the delayed onset of response (it takes several weeks before a clinical effect can be seen for most of these drugs), and the occurrence of side effects associated with pharmacotherapy, predicting response in anxiety disorders would be immensely valuable. This review surveys the literature over the past years on predictors of response to pharmacotherapy in obsessive-compulsive disorder, social anxiety disorder, panic disorder, and posttraumatic stress disorder. Prediction of treatment response may be founded on demographic and clinical variables, neurochemical and electrophysiologic parameters, imaging studies, and genetic markers.

Alleles↗
PubMed2005

Bupropion for patients with obsessive-compulsive disorder: an open-label, fixed-dose study.

OBJECTIVE: In the present study, we examined the efficacy of bupropion for patients with obsessive-compulsive disorder (OCD). METHOD: Twelve patients with OCD according to DSM-IV criteria were included in an open trial with bupropion, maximum dosage 300 mg per day, during 8 weeks. The primary efficacy parameter was the Yale-Brown Obsessive Compulsive Scale (YBOCS). A responder was defined by a reduction in score on the YBOCS of > or = 25%. Data were collected from February 2003 to July 2003. RESULTS: An intent-to-treat analysis using the last observation carried forward demonstrated that bupropion had no mean effect on OCD symptoms (mean YBOCS decrease was 1.1 +/- 9.6). Four patients improved, with a mean decrease on the YBOCS of 31%, and 2 of them met responder rate criteria. Eight patients experienced an exacerbation of OCD symptoms, with a mean increase on the YBOCS of 21%. CONCLUSION: Bupropion is not an effective treatment for OCD, but the bimodal distribution of the effect supports the notion that dopamine might be involved in the pathophysiology of OCD.

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

Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder.

BACKGROUND: Despite growing evidence for involvement of the dopaminergic system in obsessive-compulsive disorder (OCD), the functional anatomy of the dopaminergic system in the basal ganglia has been investigated sparsely. METHODS: Dopamine D(2) receptor binding was assessed in 10 medication-free OCD patients and 10 healthy control subjects, matched for age, gender, and handedness. The binding potential was measured with single photon emission computerized tomography (SPECT) and infusion of the D(2) receptor radiotracer [(123)I] iodobenzamide. With magnetic resonance imaging as reference, regions of interest (caudate and putamen) were delineated for each hemisphere and coregistered with the corresponding SPECT scans. RESULTS: Dopamine D(2) receptor binding in the left caudate nucleus was significantly lower in the patients with OCD than in healthy control subjects [F(1,18) = 7.0, p =.016]. In addition, an interhemispheric difference was observed in the patient sample. Both the D(2) receptor binding potential (df = 9, p =.012), and the volume (df = 9, p =.029) of the left caudate nucleus were statistically significantly reduced relative to the right caudate nucleus. CONCLUSIONS: This study provides in vivo evidence for abnormalities in the binding potential of the dopamine D(2) receptor, which suggest the direct involvement of the dopaminergic system in the pathophysiology of OCD.

Adolescent↗
PubMed2004

Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine.

RATIONALE: The combination of atypical antipsychotic drugs in addition to serotonin reuptake inhibitors has recently proven to be beneficial in a number of neuropsychiatric disorders, such as major depression, schizophrenia, and obsessive-compulsive disorder. OBJECTIVES: To investigate the effects of an atypical antipsychotic drug in combination with a serotonin reuptake inhibitor on extracellular serotonin [5-HT]ex, and dopamine levels [DA]ex in different brain areas. METHODS: The effects of quetiapine (10 mg/kg) with fluvoxamine (10 mg/kg) on [5-HT]ex and [DA]ex were compared in the rat dorsal striatum, prefrontal cortex, nucleus accumbens (core and shell), and thalamus by means of microdialysis coupled to HPLC with electrochemical detection. RESULTS: Quetiapine had no significant effect on [DA]ex and [5-HT]ex levels in the prefrontal cortex and thalamus, but increased [DA]ex and [5-HT]ex levels in the dorsal striatum. In the accumbens, quetiapine increased [DA]ex levels and decreased [5-HT]ex levels. Fluvoxamine increased [5-HT]ex levels in all brain areas, and also increased [DA]ex levels in the striatum. The combination of quetiapine with fluvoxamine increased [DA]ex and [5-HT]ex levels in all brain areas compared with baseline. Although neither quetiapine nor fluvoxamine in monotherapy affected [DA]ex levels in the prefrontal cortex and thalamus, the combination produced a significant increase of [DA]ex levels in these two brain areas. CONCLUSIONS: The combination of quetiapine with fluvoxamine causes a synergistic dopamine increase in the prefrontal cortex and the thalamus.

Animals↗
PubMed2004

Decreased TNF-alpha and NK activity in obsessive-compulsive disorder.

BACKGROUND: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls. RESULTS: In OCD patients, we found a significant decrease in production of TNF-alpha (p < 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003). CONCLUSIONS: Changes in TNF-alpha and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder.

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↗