Evidence map›Paper›PMID 42132958›Full record

ArticlePsychopharmacology2026

16p11.2 duplication and NMDA receptor antagonism have distinct impacts on reward learning and decision making.

Dana Mueller, Evan Knep, Angelica Velosa, Erin Giglio, Cathy S Chen, Sarah R Heilbronner, R Becket Ebitz, Patrick E Rothwell, Nicola M Grissom

Abstract read
PubMed Publisher
In one paragraph

Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Dana MuellerDepartment of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA.ORCID http://orcid.org/0000-0002-3768-6347
Evan KnepDepartment of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA.
Angelica VelosaDepartment of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA.
Erin GiglioDepartment of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA.
Cathy S ChenDepartment of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA.
Sarah R HeilbronnerDepartment of Neurosurgery, Baylor College of Medicine, Houston, TX, 77030, USA.
R Becket EbitzDepartment of Neurosciences, Université de Montréal, Quebec, H3T 1J4, Canada.
Patrick E RothwellDepartment of Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA.
Nicola M GrissomDepartment of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA. ngrissom@umn.edu.ORCID http://orcid.org/0000-0003-3630-8130

Funding

Using a computational and network neuroscience framework to study pharmacological manipulations of state representation processes in early psychosisP50MH119569 · NIMH · UNIVERSITY OF MINNESOTA · PI A DAVID REDISH, Sophia Vinogradov · 2020 to 2026
$24.5M
Sex-biased impacts of 16p11.2 variants on reward-guided choiceR01MH123661 · NIMH · UNIVERSITY OF MINNESOTA · PI GRISSOM, NICOLA · 2020 to 2024
$2.5M
Using Computation to Achieve Breakthroughs in NeuroscienceT32MH115886 · NIMH · UNIVERSITY OF MINNESOTA · PI REDISH, A DAVID · 2018 to 2022
$1.7M
Canada Excellence Research Chairs, Government of Canada FD507106NIMH NIH HHS P50 MH119569NIMH NIH HHS R01 MH123661NIMH NIH HHS T32 MH115886
6 · The paper itself

Abstract

rationale16p11.2 duplication is associated with numerous neuropsychiatric conditions at a genome-wide level, including psychosis. Mice modeling 16p11.2 duplication may provide important insights into cognitive risk factors, in particular in reward-guided decision making. NMDAR function has also been implicated in psychosis phenotypes, but whether these phenotypes differ by genetic risk factor is unknown.

objectivesWe aimed to: (1) identify sex and genotype differences in early operant training and two-arm spatial restless bandit task performance; (2) examine the effects of an NMDAR antagonist on task performance and strategy across genotypes.

methods16p11.2 duplication and wildtype mice completed a series of training schedules of escalating difficulty followed by bandit tasks. MK-801 and saline were administered in alternating sessions prior to later bandit task performance.

resultsLarge sex differences in early operant training revealed some male-biased impacts of 16p11.2 duplication, contingent on training schedule difficulty. Once on the two-arm spatial restless bandit task, 16p11.2 duplication was no longer a strong contributor to decision making. However, MK-801 decreased the tendency to stay with a rewarded choice, lowered the probability of selecting the highest rewarded option, and decreased the influence of prior outcomes on choice.

conclusionsThe male-biased vulnerability in early operant training suggests that strategies for learning early schemas or in novel environments may be impacted by 16p11.2 duplication in males. In contrast, NMDAR are influential in the ability to flexibly switch between choices, and disrupting this function significantly impairs decision making in all animals.

Indexed as

16p11.2 duplicationBanditMK-801NMDAPsychosisReinforcement learningSex differences

Identifiers

PMID42132958

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.