Nigral Stress-Induced Dopamine Release in Clinical High Risk and Antipsychotic-Naïve Schizophrenia

Overview

Journal Schizophr Bull

Publisher Oxford University Press

Specialty Psychiatry

Date 2017 Oct 17

PMID 29036383

Citations 13

Authors

Huai-Hsuan Tseng

Jeremy J Watts

Michael Kiang

Ivonne Suridjan

Alan A Wilson

Sylvain Houle

Pablo M Rusjan

Romina Mizrahi

Affiliations

Soon will be listed here.

Abstract

Background: Striatal dopamine (DA) synthesis capacity and release are elevated in schizophrenia (SCZ) and its putative prodrome, the clinical high risk (CHR) state. Striatal DA function results from the activity of midbrain DA neurons projecting mainly from the substantia nigra (SN). Elevated stress-induced DA release in SCZ and CHR was observed in the striatum; however, whether it is also elevated in the SN is unclear. The current study aims to determine whether nigral DA release in response to a validated stress task is altered in CHR and in antipsychotic-naïve SCZ. Further, we explore how DA release in the SN and striatum might be related.

Methods: 24 CHR subjects, 9 antipsychotic-naïve SCZ and 25 healthy volunteers (HV) underwent 2 positron emission tomography (PET) scans using the DA D2/3 agonist radiotracer, [11C]-(+)-PHNO, which allows simultaneous investigations of DA in the SN and striatum. Psychosocial stress-induced DA release was estimated as the percentage differences in BPND (%[11C]-(+)-PHNO displacement) between stress and sensory-motor control sessions.

Results: We observed a significant diagnostic group by session interaction, such that SCZ exhibited greater stress-induced [11C]-(+)-PHNO % displacement (25.90% ± 32.2%; mean ± SD), as compared to HVs (-10.94% ± 27.1%). Displacement in CHRs (-1.13% ± 32.2%) did not differ significantly from either HV or SCZ.

Conclusion: Our findings suggest that elevated nigral DA responsiveness to stress is observed in antipsychotic-naïve SCZ.

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