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Cited by 123Schizophrenia research and treatmentNeural and Behavioral Psychology StudiesCognitive Abilities and Testing

Mechanisms of Working Memory Impairment in Schizophrenia

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Van Snellenberg, Jared X., Girgis, Ragy R., Horga, Guillermo, van de Giessen, Elsmarieke, Slifstein, Mark, Ojeil, Najate, Weinstein, Jodi J., Moore, Holly +4 more·2016·Biological Psychiatry
DOI 10.1016/j.biopsych.2016.02.017PMC PMC4995154
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Abstract

Background The neural correlates of working memory (WM) impairment in schizophrenia remain a key puzzle in understanding the cognitive deficits and dysfunction of dorsolateral prefrontal cortex observed in this disorder. We sought to determine whether patients with schizophrenia exhibit an alteration in the inverted-U relationship between WM load and activation that we recently observed in healthy individuals and whether this could account for WM deficits in this population. Methods Medicated (n = 30) and unmedicated (n = 21) patients with schizophrenia and healthy control subjects (n = 45) performed the self-ordered WM task during functional magnetic resonance imaging. We identified regions exhibiting an altered fit to an inverted-U relationship between WM load and activation that were also predictive of WM performance. Results A blunted inverted-U response was observed in left dorsolateral prefrontal cortex in patients and was associated with behavioral deficits in WM capacity. In addition, suppression of medial prefrontal cortex during WM was reduced in patients and was associated with poorer WM capacity in patients. Finally, activation of visual cortex in the cuneus was elevated in patients and associated with improved WM capacity. Together, these findings explained 55% of the interindividual variance in WM capacity when combined with diagnostic and medication status, which alone accounted for only 22% of the variance in WM capacity. Conclusions These findings identify a novel biomarker and putative mechanism of WM deficits in patients with schizophrenia, a reduction or flattening of the inverted-U relationship between activation and WM load observed in healthy individuals in left dorsolateral prefrontal cortex.

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  • Increased dopamine release can impair working memory.

    “indicating that increased dopamine release can impair WM, as is seen in people with schizophrenia with a similar test of WM (Abi‐Dargham et al., 2002; Van Snellenberg et al., 2016).”

    From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Van Snellenberg et al., 2016

    The Introduction links dopamine function in the dorsolateral prefrontal cortex to working-memory performance and notes dopaminergic abnormalities in schizophrenia. It does not say that increased dopamine release impairs working memory; the cited paper's reference list instead includes a study titled 'Deficits in prefrontal cortical and extra-striatal dopamine release in schizophrenia.' (LLM, conf=0.84)

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Research works printed but not linked: 43

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Cited by

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Authors
Van Snellenberg, J. X., Girgis, R. R., Horga, G., van de Giessen, E., Slifstein, M., Ojeil, N., Weinstein, J. J., Moore, H., Lieberman, J. A., Shohamy, D., Smith, E. E., & Abi-Dargham, A.
Affiliations
  • Columbia University Irving Medical Center (US)
  • New York State Psychiatric Institute (US)
  • Columbia University (US)
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2016-10
Volume
80
Issue
8
Pages
617-626
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2016.02.017
PMC
PMC4995154
OpenAlex
W2282523187
Cited by
123
References
6
Citations by year
2026: 10 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 19 · 2021: 23 · 2020: 17 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 2
FWCI
8.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Amgen
  • National Institutes of Health
  • National Institute of Mental Health (U01MH076544, T32MH018870, P50MH086404, K01MH107763, K23MH101637)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
schizophrenia, working memory impairment, dorsolateral prefrontal cortex, inverted U-shaped relationship, working memory load, visual cortex activation, cuneus, antipsychotic drugs, neural markers, interindividual variability
MeSH terms
Adult, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Memory, Short-Term, Neural Pathways, Neuropsychological Tests, Occipital Lobe, Schizophrenia, Schizophrenic Psychology, Case-Control Studies, Prefrontal Cortex, Young Adult

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