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Biomedical subjects

Herman G M Westenberg

Publications and source records attributed to Herman G M Westenberg.

At least 19 recordsLinked to original sources
PubMed2007

Altered pain processing in veterans with posttraumatic stress disorder.

CONTEXT: Posttraumatic stress disorder (PTSD) is a chronic and debilitating anxiety disorder. Several brain areas related to pain processing are implicated in PTSD. To our knowledge, no functional imaging study has discussed whether patients with PTSD experience and process pain in a different way than control subjects. OBJECTIVE: To examine neural correlates of pain processing in patients with PTSD. DESIGN: The experimental procedure consisted of psychophysical assessment and neuroimaging with functional magnetic resonance imaging. Two conditions were assessed during functional magnetic resonance imaging in both experimental groups, one condition with administration of a fixed temperature of 43 degrees C (fixed-temperature condition) and the other condition with an individual temperature for each subject but with a similar affective label equaling 40% of the subjective pain intensity (individual temperature condition). SETTING: Academic outpatient unit in a department of military psychiatry in collaboration with an imaging center at a psychiatric hospital. PARTICIPANTS: Twelve male veterans with PTSD and 12 male veterans without PTSD were recruited and matched for age, region of deployment, and year of deployment. MAIN OUTCOME MEASURES: Changes in functional magnetic resonance imaging blood oxygenation level-dependent response to heat stimuli, reflecting increased and decreased activity of brain areas involved in pain processing. RESULTS: Patients with PTSD rated temperatures in the fixed-temperature assessment as less painful compared with controls. In the fixed-temperature condition, patients with PTSD revealed increased activation in the left hippocampus and decreased activation in the bilateral ventrolateral prefrontal cortex and the right amygdala. In the individual temperature condition, patients with PTSD showed increased activation in the right putamen and bilateral insula, as well as decreased activity in the right precentral gyrus and the right amygdala. CONCLUSIONS: These data provide evidence for reduced pain sensitivity in PTSD. The witnessed neural activation pattern is proposed to be related to altered pain processing in patients with PTSD.

Adult↗
PubMed2006

Long-term behavioral changes after cessation of chronic antidepressant treatment in olfactory bulbectomized rats.

BACKGROUND: Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical central nervous system changes, reminiscent of symptoms of human depression. Moreover, depression-like behavior after OBX can be reversed with antidepressant drugs. However, the lasting effects of these antidepressant drugs on behavior after cessation of treatment have never been studied. METHODS: Male rats received OBX or sham surgery. After recovery, animals received 14 consecutive daily doses of imipramine (20 mg/kg), escitalopram (5 and 10 mg/kg), or vehicle. Animals were tested in an open field after acute, sub-chronic, and chronic injections, as well as 1, 2, 6, and 10 weeks after cessation of treatment. RESULTS: The OBX-induced hyperactivity was normalized after sub-chronic administration of imipramine and escitalopram. Two weeks after treatment, activity of OBX animals was comparable to sham-treated animals, but after 6 weeks, OBX animals treated with both doses of escitalopram had returned to pre-treatment hyperactivity levels. The OBX animals treated with the high imipramine dose (20 mg/kg) retained activity levels comparable to sham-treated animals until 10 weeks after cessation of treatment. CONCLUSIONS: Chronic but not acute administration of imipramine and escitalopram normalizes OBX-induced hyperactivity. This effect continues for up to 10 weeks after cessation of treatment in a dose dependant manner.

Analysis of Variance↗
PubMed2006

Neonatal basolateral amygdala lesions affect monoamine and cannabinoid brain systems in adult rats.

There is evidence for neurodevelopment disturbances in schizophrenia. In rats, a neonatal basolateral amygdala lesion induces behavioural features in adults reminiscent of the symptomatology of schizophrenia. Dopamine plays a key role in the pathogenesis of schizophrenia, and cannabis use has been implicated in the risk for developing schizophrenia. The effects of an excitotoxic, bilateral basolateral amygdala lesion on postnatal days 7 or 21 were compared when the rats were adult. The behavioural response to a novelty challenge and the level of dopamine receptors and cannabinoid receptors in the brain using in-vitro autoradiography was determined. In brain tissue punches concentrations of monoamines and metabolites were determined by high-performance liquid chromatography. The neonatal lesion, but not the later lesion induced behavioural hyperactivity and biochemical effects. The neonatal lesion reduced the density of dopamine D2-like, but not D3-, and less markely D1-like receptors and increased dopamine turnover. These effects were observed in the mesolimbic, but not in the striatal regions. In contrast, density of cannabinoid receptors was increased in the striatal, but not the mesolimbic regions of these animals. Noradrenergic neurotransmission was reduced in both regions. The present findings contribute to the idea that the neonatal basolateral amygdala lesion induces features in adults reminiscent of the neurodevelopmental disturbances in schizophrenia, with a focus on the amygdala-prefrontal cortex-nucleus accumbens circuit.

Amygdala↗
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

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

Autonomic and neuroendocrine responses to a psychosocial stressor in adults with autistic spectrum disorder.

Objective of the study was to replicate in adults our previous findings of decreased heart rate and normal endocrine responses to stress in autistic children and to elucidate the discrepancy between autonomic and endocrine stress responses by including epinephrine, norepinephrine, oxytocin and vasopressin measurements. Ten autistic spectrum disorder (ASD) adults were compared to 14 healthy controls in their response to a psychosocial stressor (public speaking). ASD patients showed decreased heart rate, but normal cortisol responses, consistent with our prior findings in children. No differences in norepinephrine, epinephrine, oxytocin or vasopressin responses to stress were found. However, in contrast to previous findings in low functioning autistic children, ASD adults showed increased basal oxytocin levels, which may be related to developmental factors.

Adrenocorticotropic Hormone↗
PubMed2006

Pharmacotherapy for disordered sleep in post-traumatic stress disorder: a systematic review.

Sleep disorders, such as insomnia and nightmares, are common problems in post-traumatic stress disorder (PTSD), exert a strong negative influence on the quality of life and are a great challenge for clinical psychiatry. Several studies have reported on the efficacy of drugs for the treatment of PTSD-related sleep disorders. These studies have not been systematically reviewed. This is the first review on the effectiveness of sleep medication in PTSD. We performed a Medline, EMBASE and Cochrane Library Indexed search, using the keywords: PTSD, pharmacotherapy, therapy, sleep, nightmares, insomnia and review. From this database, English-language, human subject, data driven papers published after 1980 were selected. Forty eight articles are discussed. Open-label and case studies suggest efficacy for some antidepressants, anticonvulsants and atypical antipsychotics. Only a few placebo-controlled studies have been published. They show promising results for the atypical antipsychotic olanzapine, and the alpha1-adrenoceptor antagonist prazosin. In comparison to the incidence and impact of sleep complaints in PTSD, the pharmacotherapeutic armamentarium for PTSD-related sleep complaints remains poorly investigated. Some recent studies show promising results, especially for alpha1-adrenoceptor and 5-HT2 receptor antagonists. However, randomized controlled trials with larger populations need to be conducted.

Adrenergic alpha-1 Receptor Antagonists↗
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↗
PubMed2005

The influence of amphetamine on language activation: an fMRI study.

RATIONALE: Amphetamine administration has been found to affect the degree of cerebral dominance for motor control in animals. In humans, cerebral dopamine neurotransmission is also correlated to motor dominance. Since language dominance is related to motor dominance, amphetamine might also affect cerebral dominance for language. METHODS: To test this hypothesis, language activation was measured twice with functional magnetic resonance imaging in ten healthy right-handed men in a double-blind crossover design 2 h after amphetamine or placebo administration. RESULTS: Language-related activation increased significantly in task-related areas, but the individual lateralization index was not affected in the amphetamine condition as compared to placebo. CONCLUSIONS: This finding suggests that short-termed alterations in the dopaminergic neurotransmission do not affect language dominance.

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

Permanent deficits in serotonergic functioning of olfactory bulbectomized rats: an in vivo microdialysis study.

BACKGROUND: Bilateral removal of the olfactory bulbs (OBX) in rats results in a complex constellation of behavioral, neurochemical, neuroendocrine, and neuroimmune alterations, many of which are also reported in patients with major depressive disorder (MDD). Drawing on clinical findings, there has been considerable interest in the role of serotonin in the mechanism of action of OBX. However, to date, there has been no report of direct measurement of serotonergic functioning of bulbectomized animals using microdialysis. The present study describes the effects of olfactory bulbectomy on functioning of the serotonergic system. METHODS: In vivo microdialysis was performed in conscious rats that underwent OBX or sham surgery. Alterations in the functioning of the serotonergic system were assessed by administration of fluvoxamine, fenfluramine, and 3-hydroxybenzylhydrazine (NSD-1015). Animals were also repeatedly tested in an open field. RESULTS: Bilateral removal of the olfactory bulbs decreased basal extracellular levels by decreasing the releasable pool of serotonin (5-HT) in the basolateral amygdala 2 weeks after surgery and in the dorsal hippocampus 2 weeks and 5 months after surgery. Olfactory bulbectomized animals showed a lower rate of 5-HT synthesis under basal conditions. However, the capacity of the system to synthesize 5-HT was not affected. Olfactory bulbectomized rats were hyperactive in the open field. This hyperactivity remained after successive testing, indicating permanent behavioral changes. CONCLUSIONS: This microdialysis study shows that OBX has profound and long-lasting effects on serotonergic functioning and on activity levels and is therefore considered an intriguing and promising animal model for affective processes in the brain.

Animals↗
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

Metabotropic glutamate II receptor agonists in panic disorder: a double blind clinical trial with LY354740.

Preclinical studies with metabotropic glutamate (mGlu) type 2 receptor agonists have shown promising results in the treatment of anxiety. The mGlu receptor agonist LY354740 has shown anxiolytic properties in animal models of anxiety. We present the results obtained with LY354740, in a placebo-controlled double-blind randomized study with paroxetine as an active comperator in outpatients with panic disorder. This study was part of a multicentre phase II efficacy study. Patients were randomly assigned to receive LY354740 (100 or 200 mg), paroxetine (60 mg) or placebo for 9 weeks. The primary outcome parameter was the percentage of patients having no panic attacks during the final 3 weeks of treatment. Secondary outcome measures were the Panic Disorder Severity Scale (PDSS) and the clinical global impression (CGI). Patients treated on paroxetine improved on the PDSS and CGI but, due to small sample size, these effects just failed to reach statistical significance. LY354740 was well tolerated (with gastrointestinal complaints as the most common side-effects) but failed to show treatment effects that were different from placebo. Because preclinical data collectively indicate anxiolytic properties of mGlu type 2 receptor agonists, clinical studies with other agents are warranted.

Adult↗
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↗
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↗