Wolfgang Strube1, Louise Marshall2, Graziella Quattrocchi2, Simon Little3, Camelia Lucia Cimpianu4, Miriam Ulbrich4, Thomas Schneider-Axmann4, Peter Falkai4, Alkomiet Hasan5, Sven Bestmann6. 1. Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Munich, Germany. Electronic address: wolfgang.strube@med.uni-muenchen.de. 2. Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom. 3. Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California. 4. Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Munich, Germany. 5. Department of Psychiatry and Psychotherapy, Ludwig Maximillian University, Munich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg, Bezirkskrankenhaus Augsburg, University of Augsburg, Augsburg, Germany. 6. Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom; Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, Queen Square, London, United Kingdom.
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 receivingdextromethorphan 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.
RCT Entities:
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.
Authors: Wolfgang Strube; Camelia Lucia Cimpianu; Miriam Ulbrich; Ömer Faruk Öztürk; Thomas Schneider-Axmann; Peter Falkai; Louise Marshall; Sven Bestmann; Alkomiet Hasan Journal: Schizophr Bull Date: 2022-03-01 Impact factor: 7.348
Authors: D J Hauke; V Roth; P Karvelis; R A Adams; S Moritz; S Borgwardt; A O Diaconescu; C Andreou Journal: Schizophr Bull Date: 2022-06-21 Impact factor: 7.348