Abstract
Background
Impaired probabilistic reasoning and the jumping-to-conclusions reasoning bias are
hallmark features of schizophrenia (SCZ), yet the neuropharmacological basis of these
deficits remains unclear. Here we tested the hypothesis that glutamatergic neurotransmission
specifically contributes to jumping to conclusions and impaired probabilistic reasoning
in SCZ.
Methods
A total of 192 healthy participants received either NMDA receptor agonists/antagonists
(D-cycloserine/dextromethorphan), dopamine type 2 receptor agonists/antagonists (bromocriptine/haloperidol),
or placebo in a randomized, double-blind, between-subjects design. In addition, we
tested 32 healthy control participants matched to 32 psychotic inpatients with SCZ—a
state associated with compromised probabilistic reasoning due to reduced glutamatergic
neurotransmission. All experiments employed two versions of a probabilistic reasoning
(beads) task, which required participants to either sample individual amounts of sensory
information to infer correct decisions or provide explicit probability estimates for
presented sensory information. Our task instantiations assessed both information sampling
and explicit probability estimates in different probabilistic contexts (easy vs. difficult
conditions) and changing sensory information through random transitions among easy,
difficult, and ambiguous trial types.
Results
Following administration of D-cycloserine, haloperidol, and bromocriptine, healthy
participants displayed data-gathering behavior that was normal compared with placebo
and was adequate in the context of all employed task conditions and trial level difficulties.
However, healthy participants receiving dextromethorphan displayed a jumping-to-conclusions
bias, abnormally increased probability estimates, and overweighting of sensory information.
These effects were mirrored in patients with SCZ performing the same versions of the
beads task.
Conclusions
Our findings provide novel neuropharmacological evidence linking reduced glutamatergic
neurotransmission to impaired information sampling and to disrupted probabilistic
reasoning, namely to overweighting of sensory evidence, in patients with SCZ.
Keywords
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Article info
Publication history
Published online: April 08, 2020
Accepted:
March 23,
2020
Received in revised form:
March 4,
2020
Received:
November 7,
2019
Identification
Copyright
© 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Challenges Associated With Neuropharmacological Challenge StudiesBiological PsychiatryVol. 88Issue 9
- PreviewIn the current issue of Biological Psychiatry, Strube et al. (1) present a large-scale neuropharmacological challenge study in healthy individuals testing two candidate neurotransmitter–neuroreceptor mechanisms posited to underlie probabilistic reasoning deficits in actively psychotic schizophrenia patients: 1) deficient glutamatergic NMDA receptor (NMDAR) neurotransmission and 2) excessive dopaminergic D2 receptor (D2R) neurotransmission. Research on delusions in schizophrenia has implicated impairments in probabilistic reasoning.
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