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  • Hamilton, PaulLinköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten (author)

Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent C-11-raclopride positron emission tomography and functional magnetic resonance imaging investigation

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-11-30
  • NATURE PUBLISHING GROUP,2018
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:liu-153526
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-153526URI
  • https://doi.org/10.1038/s41398-018-0316-2DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • Funding Agencies|Weston Havens Foundation
  • Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the corticostriatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and C-11-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and C-11-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

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  • Sacchet, Matthew D.Stanford Univ, CA 94305 USA (author)
  • Hjornevik, TrineOslo Univ Hosp, Norway; Norwegian Med Cyclotron Ctr, Norway; Stanford Univ, CA 94305 USA (author)
  • Chin, Frederick T.Stanford Univ, CA 94305 USA (author)
  • Shen, BinStanford Univ, CA 94305 USA (author)
  • Kämpe, RobinLinköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten(Swepub:liu)robka95 (author)
  • Park, Jun HyungStanford Univ, CA 94305 USA (author)
  • Knutson, Brian D.Stanford Univ, CA USA (author)
  • Williams, Leanne M.Stanford Univ, CA 94305 USA (author)
  • Borg, NicholasStanford Univ, CA USA (author)
  • Zaharchuk, GregStanford Univ, CA 94305 USA (author)
  • Camacho, M. CatalinaUniv Pittsburgh, PA 15260 USA (author)
  • Mackey, SeanStanford Univ, CA 94305 USA (author)
  • Heilig, MarkusLinköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Region Östergötland, Psykiatriska kliniken(Swepub:liu)marhe41 (author)
  • Drevets, Wayne C.Janssen Res and Dev LLC, NJ USA (author)
  • Glover, Gary H.Stanford Univ, CA 94305 USA (author)
  • Gambhir, Sanjiv S.Stanford Univ, CA 94305 USA (author)
  • Gotlib, Ian H.Stanford Univ, CA USA (author)
  • Linköpings universitetCentrum för social och affektiv neurovetenskap (creator_code:org_t)

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  • In:Translational Psychiatry: NATURE PUBLISHING GROUP82158-3188

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