Anxiety Disorders: van den Heuvel OA

van Grootheest DS, van den Heuvel OA, Cath DC, van Oppen P, van Balkom AJ. · Vrije Universiteit, afd. Biologische Psychologie, Van der Boechorststraat 1, 1081 BT Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #19024062 No free full text.

Abstract: Obsessive-compulsive disorder is a complex psychiatric disorder characterised by obsessions and/or compulsions. Obsessive-compulsive disorder has a relatively high prevalence and is a highly disabling disease. The disorder is associated with shame, which causes long delays in accessing treatment. Obsessive-compulsive disorder is caused by a complex interplay between genetic and environmental factors. Effective treatments exist in the form of either pharmacotherapy--clomipramine or selective serotonin reuptake inhibitors--or cognitive behaviour therapy.

Mataix-Cols D, van den Heuvel OA. · Department of Psychological Medicine, King's College London, Institute of Psychiatry, London SE5 8AF, UK. · Psychiatr Clin North Am. · Pubmed #16650715 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) often co-occurs with other anxiety disorders and a number of other disorders of similar phenomenology known as the "OCD spectrum" disorders. Neurobiologically, it is unclear how all these disorders relate to each other.The picture is further complicated by the clinical heterogeneity of OCD itself. This article reviews the literature on the common and distinct neural correlates of OCD, its symptom dimensions, and other anxiety and OCD spectrum disorders with the hope of providing a conceptual and heuristic framework to help understand the relationship between these phenomena.

van den Heuvel OA, van de Wetering BJ, Veltman DJ, Pauls DL. · Department of Psychiatry and the Clinical PET Center, Academic Hospital Free University, Amsterdam, The Netherlands. · J Clin Psychiatry. · Pubmed #11078037 No free full text.

Abstract: BACKGROUND: A review of the studies examining the genetic etiology of panic disorder shows the familial nature of the disorder and demonstrates that the etiology is greatly influenced by genetic factors. Strong evidence for vertical transmission in family studies led to molecular genetic studies, of which association designs appear promising, particularly when based on trait markers. DATA SOURCES: The MEDLINE and PsycLIT databases were searched for all reports published between 1966 and 2000 containing the keywords panic, genetic, twin, adoption, linkage, association, and QTL. CONCLUSION: We conclude that the multifactorial nature of panic disorder requires a multidisciplinary approach to gain insight into the determinants of the phenotype and the interaction of environmental and genetic factors.

Mesina CT, Boellaard R, van den Heuvel OA, Veltman DJ, Jongbloed G, van der Vaart AW, Lammertsma AA. · PET Center, VU University Medical Center, Amsterdam, The Netherlands. · Neuroimage. · Pubmed #14568460 No free full text.

Abstract: The outcome of Statistical Parametric Mapping (SPM) analyses of PET activation studies depends among others, on the quality of reconstructed data. In general, filtered back-projection (FBP) is used for reconstruction in PET activation studies. There is, however, increasing interest in iterative reconstruction algorithms such as ordered subset expectation maximization (OSEM) algorithms. The aim of the present study was to investigate the effects of reconstruction techniques and attenuation correction (AC) on the detection of activation foci following statistical analysis with SPM. First, a replicate study was performed to assess the effects of the reconstruction method on pixel variance. Second, a phantom study was performed to evaluate the influence of both locations of an activated area and applied reconstruction method on SPM outcome. A volumetric method was used to compute the number of false positive voxels for all reconstructions. In addition, average t values within activation foci and for false positive voxels were calculated. For the assessment of the effects of reconstruction on clinical data, a group of 11 patients was studied. For all reconstructions SPM maps were created and compared. Both the clinical and the phantom data showed that use of iterative reconstruction methods reduced false positive results, while showing similar SPM results within activated areas as FBP. Reconstruction of data without attenuation correction reduced noise for FBP only, but did not affect the quality of SPM results for OSEM. It is concluded that OSEM is a good alternative for FBP reconstructions providing SPM results with less noise.

van den Heuvel OA, Veltman DJ, Groenewegen HJ, Witter MP, Merkelbach J, Cath DC, van Balkom AJ, van Oppen P, van Dyck R. · Departments of Psychiatry and Anatomy, VU University Medical Center, Amsterdam, the Netherlands. · Arch Gen Psychiatry. · Pubmed #16061770 links to  free full text

Abstract: CONTEXT: Attentional bias to disease-relevant emotional cues is considered to be pathogenetically relevant in anxiety disorders. OBJECTIVE: To investigate functional neural correlates and disease specificity of attentional bias across different anxiety disorders. DESIGN: A cognitive and emotional Stroop task, consisting of congruent and incongruent color words, obsessive-compulsive disorder (OCD)-related and panic-related negative words, and neutral words, was used in 3 patient groups and a control group during functional magnetic resonance imaging. SETTING: Academic outpatient department for anxiety disorders.Patients and PARTICIPANTS: Medication-free patients with OCD (n = 16), panic disorder (PD) (n = 15), and hypochondriasis (n = 13) and 19 controls. MAIN OUTCOME MEASURE: Voxel-wise analyses of cerebral blood flow changes for contrasts of interest (incongruent vs congruent color words, OCD-related vs neutral words, and panic-related vs neutral words) within and between groups. RESULTS: During incongruent vs congruent color naming, all patient groups recruited additional posterior brain regions relative to controls, but performance was impaired only in OCD. In OCD, color naming OCD-related, but not PD-related, words correlated with increased activation of frontal-striatal and temporal regions, although performance was unimpaired. In contrast, in PD, increased frontal-striatal involvement was found during color naming both OCD-related and panic-related words. In PD, color naming panic-related words was slowed and correlated with increased activation of the right amygdala and hippocampus. Patients with hypochondriasis showed a similar activation pattern to patients with PD. CONCLUSIONS: Our results support the hypothesis of increased distractibility for irrelevant information in patients with OCD, PD, and hypochondriasis associated with frontal-striatal and limbic involvement compared with controls. Although patients with OCD did not display an attentional bias in behavior relative to controls, there was a clear, specific neural response during color naming OCD-related words, involving mainly ventral brain regions. In contrast, generalized emotional interference effects were found in PD and hypochondriasis, involving ventral and widespread dorsal brain regions, reflecting not only unconscious emotional stimulus processing but also increased cognitive elaboration.

van den Heuvel OA, Veltman DJ, Groenewegen HJ, Cath DC, van Balkom AJ, van Hartskamp J, Barkhof F, van Dyck R. · Departments of Psychiatry, Anatomy, and Radiology and Outpatient Clinic for Anxiety Disorders, GGZ Buitenamstel, VU University Medical Center, Amsterdam, The Netherlands. · Arch Gen Psychiatry. · Pubmed #15753243 links to  free full text

Abstract: BACKGROUND: Dysfunction of frontal-striatal, particularly orbitofrontal-striatal, circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD), characterized by obsessions, ritualistic behavior, anxiety, and specific cognitive impairments. In addition, neuropsychological studies in OCD have reported impairments in visuospatial tasks and executive functions, such as planning. OBJECTIVE: To determine whether dorsal prefrontal-striatal dysfunction mediates planning impairment in patients with OCD. DESIGN: A parametric self-paced pseudorandomized event-related functional magnetic resonance imaging version of the Tower of London task was used in 22 medication-free patients with OCD and 22 healthy control subjects. This paradigm, allowing flexible responding and post hoc classification of correct responses, was developed to compare groups likely to differ in performance. RESULTS: Behavioral results showed significant planning impairments in OCD patients compared with control subjects. During planning, decreased frontal-striatal responsiveness was found in OCD patients, mainly in dorsolateral prefrontal cortex and caudate nucleus. In addition, OCD patients showed increased, presumably compensatory, involvement of brain areas known to play a role in performance monitoring and short-term memory processing, such as anterior cingulate, ventrolateral prefrontal, and parahippocampal cortices. CONCLUSIONS: These findings support the hypothesis that decreased dorsal prefrontal-striatal responsiveness is associated with impaired planning capacity in OCD patients. Because the described frontal-striatal dysfunction in OCD is independent of state anxiety and disease symptom severity, we conclude that executive impairment is a core feature in OCD.

van den Heuvel OA, Veltman DJ, Groenewegen HJ, Dolan RJ, Cath DC, Boellaard R, Mesina CT, van Balkom AJ, van Oppen P, Witter MP, Lammertsma AA, van Dyck R. · Department of Psychiatry, VU University Medical Center and GGZ Buitenamstel, Valeriusplein 9, 1075 BG Amsterdam, The Netherlands. · Psychiatry Res. · Pubmed #15664794 No free full text.

Abstract: Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

van den Heuvel OA, Boellaard R, Veltman DJ, Mesina C, Lammertsma AA. · Clinical PET Centre, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, the Netherlands. · Neuroimage. · Pubmed #12948706 No free full text.

Abstract: Motion-induced misalignment between transmission and emission scans can result in erroneous estimation of regional tissue activity concentrations. If this motion is of a random nature, mismatch between transmission and emission scans is likely to result in diminished signal-to-noise ratios. In the case of task-related motion, however, corresponding systematic reconstruction artefacts may lead to false-positive or false-negative results. The purpose of the present study was to investigate whether implementation of an image registration (IR) method, which allows for motion-corrected attenuation correction, would improve accuracy of H(2)(15)O PET activation studies. To evaluate the performance of this method, phantom studies as well as studies in human subjects were performed. Results were compared with three alternative methods: standard attenuation correction without motion correction, calculated attenuation correction, and no attenuation correction. The phantom measurements showed that, for quantitative assessment of regional activity concentrations, the IR method was superior to the other attenuation correction methods. In a single-subject study with intentional task-related motion during a visual stimulation paradigm, false-positive results, obtained with the standard attenuation correction method, disappeared after attenuation correction using the IR method. Finally, a group analysis of 11 patients indicated that an increase in signal-to-noise ratio was obtained with the IR method. Therefore, in our view, the IR method should be considered as a first choice for attenuation correction in PET activation studies.