PMID- 33941857
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20230315
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 46
IP  - 8
DP  - 2021 Jul
TI  - Interactions between hippocampal activity and striatal dopamine in people at 
      clinical high risk for psychosis: relationship to adverse outcomes.
PG  - 1468-1474
LID - 10.1038/s41386-021-01019-0 [doi]
AB  - Preclinical models propose that increased hippocampal activity drives subcortical 
      dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. 
      Here, we used multimodal neuroimaging to examine the relationship between 
      hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis 
      capacity in people at clinical high risk (CHR) for psychosis and investigated its 
      association with subsequent clinical and functional outcomes. Ninety-five 
      participants (67 CHR and 28 healthy controls) underwent arterial spin labeling 
      MRI and (18)F-DOPA PET imaging at baseline. CHR participants were followed up for 
      a median of 15 months to determine functional outcomes with the global assessment 
      of function (GAF) scale and clinical outcomes using the comprehensive assessment 
      of at-risk mental states (CAARMS). CHR participants with poor functional outcomes 
      (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared 
      to CHRs with good functional outcomes (GAF >/= 65, n = 25) (p(fwe) = 0.026). The 
      relationship between rCBF in this right hippocampal region and striatal dopamine 
      synthesis capacity was also significantly different between groups 
      (p(fwe) = 0.035); the association was negative in CHR with poor outcomes 
      (p(fwe) = 0.012), but non-significant in CHR with good outcomes. Furthermore, the 
      correlation between right hippocampal rCBF and striatal dopamine function 
      predicted a longitudinal increase in the severity of positive psychotic symptoms 
      within the total CHR group (p = 0.041). There were no differences in rCBF, 
      dopamine, or their associations in the total CHR group relative to controls. 
      These findings indicate that altered interactions between the hippocampus and the 
      subcortical dopamine system are implicated in the pathophysiology of adverse 
      outcomes in the CHR state.
FAU - Modinos, Gemma
AU  - Modinos G
AUID- ORCID: 0000-0002-7870-066X
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK. gemma.modinos@kcl.ac.uk.
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, 
      King's College London, London, UK. gemma.modinos@kcl.ac.uk.
AD  - MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK. 
      gemma.modinos@kcl.ac.uk.
FAU - Richter, Anja
AU  - Richter A
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
FAU - Egerton, Alice
AU  - Egerton A
AUID- ORCID: 0000-0003-2939-064X
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
FAU - Bonoldi, Ilaria
AU  - Bonoldi I
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
FAU - Azis, Matilda
AU  - Azis M
AUID- ORCID: 0000-0001-8164-0357
AD  - Department of Psychology, Northwestern University, Chicago, IL, USA.
FAU - Antoniades, Mathilde
AU  - Antoniades M
AD  - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 
      USA.
FAU - Bossong, Matthijs
AU  - Bossong M
AD  - Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Centre 
      Utrecht, Utrecht, The Netherlands.
FAU - Crossley, Nicolas
AU  - Crossley N
AD  - Department of Psychiatry, School of Medicine, Pontificia Universidad Catolica de 
      Chile, Santiago, Chile.
FAU - Perez, Jesus
AU  - Perez J
AD  - CAMEO Early Intervention in Psychosis Service, Cambridgeshire and Peterborough 
      NHS Foundation Trust, Cambridge, UK.
AD  - Department of Psychiatry, University of Cambridge, Cambridge, UK.
AD  - Department of Neuroscience, Instituto de Investigacion Biomedica de Salamanca 
      (IBSAL), University of Salamanca, Salamanca, Spain.
FAU - Stone, James M
AU  - Stone JM
AUID- ORCID: 0000-0003-3051-0135
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, 
      King's College London, London, UK.
AD  - South London and Maudsley Foundation NHS Trust, Maudsley Hospital, London, UK.
FAU - Veronese, Mattia
AU  - Veronese M
AUID- ORCID: 0000-0003-3562-0683
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, 
      King's College London, London, UK.
FAU - Zelaya, Fernando
AU  - Zelaya F
AD  - Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, 
      King's College London, London, UK.
FAU - Grace, Anthony A
AU  - Grace AA
AD  - Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, 
      Pittsburgh, PA, USA.
FAU - Howes, Oliver D
AU  - Howes OD
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
AD  - MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
AD  - South London and Maudsley Foundation NHS Trust, Maudsley Hospital, London, UK.
AD  - MRC London Institute of Medical Sciences, Imperial College London, Hammersmith 
      Hospital, London, UK.
FAU - Allen, Paul
AU  - Allen P
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
AD  - Department of Psychology, University of Roehampton, London, UK.
FAU - McGuire, Philip
AU  - McGuire P
AD  - Department of Psychosis Studies, Institute of Psychiatry, Psychology and 
      Neuroscience, King's College London, London, UK.
AD  - MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
AD  - South London and Maudsley Foundation NHS Trust, Maudsley Hospital, London, UK.
LA  - eng
GR  - 091667/WT_/Wellcome Trust/United Kingdom
GR  - MC_U120097115/MRC_/Medical Research Council/United Kingdom
GR  - G0700995/MRC_/Medical Research Council/United Kingdom
GR  - 202397/Z/16/Z/WT_/Wellcome Trust/United Kingdom
GR  - MR/N026063/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210503
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Corpus Striatum/diagnostic imaging
MH  - *Dopamine
MH  - Hippocampus/diagnostic imaging
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - *Psychotic Disorders/diagnostic imaging
PMC - PMC8209204
EDAT- 2021/05/05 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/05/03
CRDT- 2021/05/04 06:45
PHST- 2021/02/01 00:00 [received]
PHST- 2021/04/08 00:00 [accepted]
PHST- 2021/04/06 00:00 [revised]
PHST- 2021/05/05 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/05/04 06:45 [entrez]
PHST- 2021/05/03 00:00 [pmc-release]
AID - 10.1038/s41386-021-01019-0 [pii]
AID - 1019 [pii]
AID - 10.1038/s41386-021-01019-0 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2021 Jul;46(8):1468-1474. doi: 
      10.1038/s41386-021-01019-0. Epub 2021 May 3.