Synaptic changes in psychiatric and neurological disorders: state-of-the art of in vivo imaging.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
12 Aug 2024
12 Aug 2024
Historique:
received:
27
03
2024
accepted:
19
07
2024
revised:
03
07
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
12
8
2024
Statut:
aheadofprint
Résumé
Synapses are implicated in many neuropsychiatric illnesses. Here, we provide an overview of in vivo techniques to index synaptic markers in patients. Several positron emission tomography (PET) tracers for synaptic vesicle glycoprotein 2 A (SV2A) show good reliability and selectivity. We review over 50 clinical studies including over 1700 participants, and compare findings in healthy ageing and across disorders, including addiction, schizophrenia, depression, posttraumatic stress disorder, and neurodegenerative disorders, including tauopathies, Huntington's disease and α-synucleinopathies. These show lower SV2A measures in cortical brain regions across most of these disorders relative to healthy volunteers, with the most well-replicated findings in tauopathies, whilst changes in Huntington's chorea, Parkinson's disease, corticobasal degeneration and progressive supranuclear palsy are predominantly subcortical. SV2A PET measures are correlated with functional connectivity across brain networks, and a number of other measures of brain function, including glucose metabolism. However, the majority of studies found no relationship between grey matter volume measured with magnetic resonance imaging and SV2A PET measures. Cognitive dysfunction, in domains including working memory and executive function, show replicated inverse relationships with SV2A measures across diagnoses, and initial findings also suggest transdiagnostic relationships with mood and anxiety symptoms. This suggests that synaptic abnormalities could be a common pathophysiological substrate underlying cognitive and, potentially, affective symptoms. We consider limitations of evidence and future directions; highlighting the need to develop postsynaptic imaging markers and for longitudinal studies to test causal mechanisms.
Identifiants
pubmed: 39134769
doi: 10.1038/s41386-024-01943-x
pii: 10.1038/s41386-024-01943-x
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : RCUK | Medical Research Council (MRC)
ID : MC_U120097115
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/W005557/1
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/V013734/1
Organisme : Wellcome Trust (Wellcome)
ID : 094849/Z/10/Z
Informations de copyright
© 2024. The Author(s).
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