title: Extrastriatal dopamine D2-receptor availability in social anxiety disorder.
abstract: Alterations in the dopamine system are hypothesized to influence the expression of social anxiety disorder (SAD) symptoms. However, molecular imaging studies comparing dopamine function between patients and control subjects have yielded conflicting results. Importantly, while all previous investigations focused on the striatum, findings from activation and blood flow studies indicate that prefrontal and limbic brain regions have a central role in the pathophysiology. The objective of this study was to investigate extrastriatal dopamine D2-receptor (D2-R) availability in SAD. We examined 12 SAD patients and 16 healthy controls using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB457. Parametric images of D2-R binding potential were derived using the Logan graphical method with cerebellum as reference region. Two-tailed one-way independent ANCOVAs, with age as covariate, were used to examine differences in D2-R availability between groups using both region-based and voxel-wise analyses. The region-based analysis showed a medium effect size of higher D2-R levels in the orbitofrontal cortex (OFC) in patients, although this result did not remain significant after correction for multiple comparisons. The voxel-wise comparison revealed elevated D2-R availability in patients within OFC and right dorsolateral prefrontal cortex after correction for multiple comparisons. These preliminary results suggest that an aberrant extrastriatal dopamine system may be part of the disease mechanism in SAD.
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden. Electronic address: pontus.plaven-sigray@ki.se.
authors.forename: Pontus
authors.initials: P
authors.lastname: Plavén-Sigray
authors.affiliation: Stockholm Health Care Services, Stockholm County Council, Sweden; Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Hedman
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Victorsson
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Granville J
authors.initials: GJ
authors.lastname: Matheson
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Forsberg
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Djurfeldt
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Rück
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Lindefors
authors.affiliation: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Cervenka
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000072861:Phobia, Social / Q000000981:diagnostic imaging / Q000473:pathology* / Q000534:rehabilitation*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457
keywords: Dopamine; Dopamine D2; Phobic disorders; Positron-Emission tomography; Prefrontal cortex; Receptors