Striatal dopamine D-2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis

Oswald J. N. Bloemen, Mariken B. de Koning, Tobias Gleich, Julia Meijer, Lieuwe de Haan, Don H. Linszen, Jan Booij, Therese A. M. J. van Amelsvoort*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Altered striatal dopaminergic neurotransmission is thought to be fundamental to schizophrenia. Increased presynaptic dopaminergic activity ([F-18]-DOPA PET) may predate the onset of psychotic symptoms and correlates to clinical symptoms in subjects at Ultra High Risk (UHR) for developing psychosis. Postsynaptic dopaminergic neurotransmission has not been investigated yet in UHR patients. We hypothesized that synaptic dopamine concentration would be increased in UHR patients, and that synaptic dopamine concentration would be related to symptom severity. 14 UHR patients and 15 age and IQ matched controls completed an [I-123]-IBZM SPECT scan at baseline and again after dopamine depletion with alpha-methyl-para-tyrosine (AMPT). We measured changes in radiotracer binding potential, compared these between UHR patients and controls, and correlated these to symptom severity. The UHR group as a whole did not differ significantly from controls. AMPT significantly reduced symptom severity in the UHR group (p = 0.014). Higher synaptic dopamine concentration predicted larger reduction of positive symptoms following depletion in the UHR group (p = 0.01). In UHR patients, positive symptoms responded to dopamine depletion, comparable to observations in schizophrenia, suggesting a similar mechanism. Higher synaptic dopamine concentration was associated with more severe positive symptoms and a greater reduction of these symptoms following depletion.
Original languageEnglish
Pages (from-to)126-132
JournalEuropean Neuropsychopharmacology
Issue number2
Publication statusPublished - Feb 2013


  • UHR
  • Schizophrenia
  • Depletion
  • AMPT
  • Dopamine
  • Striatum

Cite this