title: Pre-pulse inhibition and striatal dopamine in subjects at an ultra-high risk for psychosis.
abstract: Reduced prepulse inhibition (PPI) of the acoustic startle response is thought to represent a robust biomarker in schizophrenia. Reduced PPI has been demonstrated in subjects at ultra high risk (UHR) for developing psychosis. Imaging studies report disruption of striatal dopaminergic neurotransmission in patients with schizophrenia. First, we compared the PPI of the acoustic startle response in UHR subjects versus healthy controls, to see if we could replicate previous findings of reduced PPI; secondly, we investigated our hypothesis that PPI would be negatively correlated with striatal synaptic dopamine (DA) concentration. We measured the startle reactivity and PPI of the acoustic startle response in 14 UHR subjects, and 14 age- and gender-matched healthy controls. Imaging of 11 UHR subjects and 11 healthy controls was completed by an [(123)I]-IBZM (radiotracer for dopamine D2/3 receptors) SPECT, at baseline and again after DA depletion with alpha-methyl-para-tyrosine (AMPT). The percentage change in striatal [(123)I]-IBZM radiotracer binding potential is a proxy of striatal synaptic DA concentration. UHR subjects showed reduced PPI, compared to control subjects. In both UHR and control subjects, there were no significant correlations between striatal synaptic DA concentration and PPI. We provide further evidence for the hypothesis that these two biomarkers are measuring different aspects of pathophysiology.
authors: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Arkin Mental Health Care, Amsterdam, The Netherlands m.b.dekoning@amc.uva.nl.
authors: Mariken B
authors: MB
authors: De Koning
authors: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Oswald Jn
authors: OJ
authors: Bloemen
authors: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Esther DA
authors: ED
authors: Van Duin
authors: Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Jan
authors: J
authors: Booij
authors: Centre for Women's Mental Health, Manchester Academy of Health Sciences, University of Manchester, Manchester, UK.
authors: Kathryn M
authors: KM
authors: Abel
authors: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Lieuwe
authors: L
authors: De Haan
authors: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Don H
authors: DH
authors: Linszen
authors: Department of Psychiatry, Maastricht University, Maastricht, The Netherlands Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Thérèse Amj
authors: TA
authors: Van Amelsvoort
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001549:Benzamides / Q000008:administration & dosage; D016022:Case-Control Studies; D003287:Contrast Media / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D065808:Prepulse Inhibition; D011618:Psychotic Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D011759:Pyrrolidines / Q000008:administration & dosage; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D013216:Reflex, Startle; D018570:Risk Assessment; D012307:Risk Factors; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D001549:Benzamides; D003287:Contrast Media; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D004298:Dopamine
keywords: Acoustic startle response; biomarkers; dopamine; dopamine receptor; high risk; imaging; pre-pulse inhibition; psychosis; schizophrenia; sensorimotor gating