Digitala Vetenskapliga Arkivet

Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.ORCID-id: 0000-0002-4784-5196
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.ORCID-id: 0000-0003-2516-9075
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.ORCID-id: 0000-0001-5310-6843
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.ORCID-id: 0000-0003-1214-2586
Vise andre og tillknytning
2021 (engelsk)Inngår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, nr 8, s. 3970-3979Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.

sted, utgiver, år, opplag, sider
Springer Nature, 2021. Vol. 26, nr 8, s. 3970-3979
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-400349DOI: 10.1038/s41380-019-0618-7ISI: 000731712800027PubMedID: 31822819OAI: oai:DiVA.org:uu-400349DiVA, id: diva2:1381025
Forskningsfinansiär
Swedish Research CouncilRiksbankens JubileumsfondTilgjengelig fra: 2019-12-19 Laget: 2019-12-19 Sist oppdatert: 2024-01-15bibliografisk kontrollert
Inngår i avhandling
1. Imaging serotonin and dopamine transporters in social anxiety disorder: Characterization, treatment and expectancy effects
Åpne denne publikasjonen i ny fane eller vindu >>Imaging serotonin and dopamine transporters in social anxiety disorder: Characterization, treatment and expectancy effects
2020 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The monoamines serotonin and dopamine are likely to be involved in the pathophysiology of social anxiety and other affective disorders, but their respective contributions and putative interactions in the causes and cures of these disorders are still not well understood. It is also largely unknown if and how expectations of treatment success affect brain neurochemistry and neural activations, and if expectations interact with antidepressants like selective serotonin reuptake inhibitors (SSRIs). In this thesis some of these issues were addressed by use of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Using the highly selective radiotracers [11C]DASB and [11C]PE2I to characterize the availability of serotonin (SERT) and dopamine (DAT) transporter proteins, study I compared non-displaceable binding potentials (BPND), probing the transporters, between patients with social anxiety disorder and healthy controls. Increased SERT binding was observed in the reward related region nucleus accumbens (NAcc), in the social anxiety group. Moreover, increased DAT binding was associated with severity of the disorder and social anxiety was also associated with higher SERT-DAT co-expression in fear- and reward-related areas, including the amygdala and NAcc. Study II showed that verbal instructions regarding expected treatment efficacy strongly affected the clinical outcome of SSRI-treatment. Overt treatment, when patients with social anxiety disorder were correctly informed, was vastly superior to covert SSRI treatment, when patients expected an ineffective placebo. Groups were also differentiated on objective brain activity measures. Study III further demonstrated different SERT and DAT binding changes in limbic and striatal areas with overt as compared to covert SSRI-treatment. Decreased DAT BPND in the striatum, as assessed with PET, correlated with improvement in the overt group, suggesting increased dopaminergic signalling. Study IV compared treatment-induced changes in SERT and DAT binding after cognitive-behavior therapy (CBT) combined with an SSRI or placebo in patients with social anxiety disorder. Both groups showed initial co-expression similar to study I. The SSRI+CBT and placebo+CBT combinations yielded dissimilar transporter change patterns. Higher SERT occupancy in the NAcc correlated with reduced symptoms and this relationship was moderated by the change in DAT BPND. The results of this thesis support that functional interactions between serotonin and dopamine modulate social anxiety symptomatology and are important brain targets for successful treatment. Further it demonstrates that the treatment success of SSRIs in social anxiety disorder depends on how the treatment is presented. These results can be informative for the practice of clinicians, but also highlights an ethical dilemma because a large portion of the total treatment effects is elicited by processes within the patient itself.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2020. s. 85
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 176
Emneord
PET, serotonin, dopamine, placebo, SSRI, CBT, MRI
HSV kategori
Forskningsprogram
Psykologi; Psykiatri; Radiologi
Identifikatorer
urn:nbn:se:uu:diva-406312 (URN)978-91-513-0895-1 (ISBN)
Disputas
2020-04-24, Sal XI, Universitetshuset, Biskopsgatan 3, Uppsala, 10:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2020-04-02 Laget: 2020-03-06 Sist oppdatert: 2020-05-19

Open Access i DiVA

fulltext(1291 kB)599 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 1291 kBChecksum SHA-512
4eecf55077dc6ef9f515889a0082d6e1c1abe420f2f445d25ad3c1a282788c7866ce5417ef27f63ab8d47d59d5136dfa33bd11629f079927218d64056bc68ee6
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Søk i DiVA

Av forfatter/redaktør
Hjorth, OlofFrick, AndreasGingnell, MalinHoppe, Johanna M.Faria, VandaAlaie, ImanMånsson, Kristoffer N TWahlstedt, KurtJonasson, MyLubberink, MarkAntoni, GunnarFredrikson, MatsFurmark, Tomas
Av organisasjonen
I samme tidsskrift
Molecular Psychiatry

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 599 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 305 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf