Neurochemical effects of oxytocin in people at clinical high risk for psychosis

TY - JOUR

T1 - Neurochemical effects of oxytocin in people at clinical high risk for psychosis

AU - Davies, Catherine

AU - Rutigliano, Grazia

AU - Stone, James

AU - Zelaya, Fernando

AU - Allen, Paul

AU - Morrison, Paul D.

AU - Williams , Steve

AU - Taylor, David

AU - Lythgoe, David

AU - McGuire, Philip K.

AU - Fusar-Poli, Paolo

PY - 2019/3/28

Y1 - 2019/3/28

N2 - Alterations in neurochemical metabolites are thought to play a role in the pathophysiology of psychosis onset. Oxytocin, a neuropeptide with prosocial and anxiolytic properties, modulates glutamate neurotransmission in preclinical models but its neurochemical effects in people at high risk for psychosis are unknown. We used proton magnetic resonance spectroscopy (1H-MRS) to examine the effects of intranasal oxytocin on glutamate and other metabolites in people at Clinical High Risk for Psychosis (CHR-P) in a double-blind, placebo- controlled, crossover design. 30 CHR-P males were studied on two occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on the concentration of glutamate, glutamate+glutamine and other metabolites (choline, N- acetylaspartate, myo-inositol) scaled to creatine were examined in the left thalamus, anterior cingulate cortex (ACC) and left hippocampus, starting approximately 75, 84 and 93 minutes post-dosing, respectively. Relative to placebo, administration of oxytocin was associated with an increase in choline levels in the ACC (p=.008, Cohen’s d =0.54). There were no other significant effects on metabolite concentrations (all p>.05). Our findings suggest that, at ~75-93 minutes post-dosing, a single dose of intranasal oxytocin does not alter levels of neurochemical metabolites in the thalamus, ACC, or hippocampus in those at CHR-P, aside from potential effects on choline in the ACC. © 2019, Elsevier. The attached document (embargoed until 28/03/2020) is an author produced version of a paper published in EUROPEAN NEUROPSYCHOPHARMACOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

AB - Alterations in neurochemical metabolites are thought to play a role in the pathophysiology of psychosis onset. Oxytocin, a neuropeptide with prosocial and anxiolytic properties, modulates glutamate neurotransmission in preclinical models but its neurochemical effects in people at high risk for psychosis are unknown. We used proton magnetic resonance spectroscopy (1H-MRS) to examine the effects of intranasal oxytocin on glutamate and other metabolites in people at Clinical High Risk for Psychosis (CHR-P) in a double-blind, placebo- controlled, crossover design. 30 CHR-P males were studied on two occasions, once after 40IU intranasal oxytocin and once after placebo. The effects of oxytocin on the concentration of glutamate, glutamate+glutamine and other metabolites (choline, N- acetylaspartate, myo-inositol) scaled to creatine were examined in the left thalamus, anterior cingulate cortex (ACC) and left hippocampus, starting approximately 75, 84 and 93 minutes post-dosing, respectively. Relative to placebo, administration of oxytocin was associated with an increase in choline levels in the ACC (p=.008, Cohen’s d =0.54). There were no other significant effects on metabolite concentrations (all p>.05). Our findings suggest that, at ~75-93 minutes post-dosing, a single dose of intranasal oxytocin does not alter levels of neurochemical metabolites in the thalamus, ACC, or hippocampus in those at CHR-P, aside from potential effects on choline in the ACC. © 2019, Elsevier. The attached document (embargoed until 28/03/2020) is an author produced version of a paper published in EUROPEAN NEUROPSYCHOPHARMACOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

U2 - 10.1016/j.euroneuro.2019.03.008

DO - 10.1016/j.euroneuro.2019.03.008

M3 - Article

SN - 0924-977X

VL - 29

SP - 601

EP - 615

JO - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

IS - 5

ER -