Cited by 840Psychological Testing and AssessmentHistorical and Modern Theater StudiesCognitive Abilities and Testing

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index; none of the 55 sources its claims cite is checked for support yet.

Digit Symbol Substitution Test: The Case for Sensitivity Over Specificity in Neuropsychological Testing

Open access
Jaeger, Judith·2018·Journal of Clinical Psychopharmacology

Abstract

Purpose/Background: Development of the Digit Symbol Substitution Test (DSST) was initiated over a century ago as an experimental tool to understand human associative learning. Its clinical utility, owing to its brevity and high discriminant validity, was first recognized in the 1940s, and now the DSST is among the most commonly used tests in clinical neuropsychology. Methods: Specific studies and articles were reviewed to illustrate what the test measures, to evaluate its sensitivity to change, and to discuss its use in clinical practice. Results: The DSST is a valid and sensitive measure of cognitive dysfunction impacted by many domains. Performance on the DSST correlates with real-world functional outcomes (eg, the ability to accomplish everyday tasks) and recovery from functional disability in a range of psychiatric conditions including schizophrenia and major depressive disorder. Importantly, the DSST has been demonstrated to be sensitive to changes in cognitive functioning in patients with major depressive disorder and offers promise as a clinical decision-making tool for monitoring treatment effects in this and other disorders affecting cognition. Implications/Conclusions: The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function across a wide range of clinical populations but has low specificity to determine exactly which cognitive domain has been affected. However, the DSST offers a practical and effective method to monitor cognitive functions over time in clinical practice.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

The Digit Symbol Substitution Test (DSST) is a brief, widely used paper-and-pencil measure that is sensitive to cognitive dysfunction and change across many clinical populations, including major depressive disorder (MDD). It is polyfactorial and has low specificity for identifying which cognitive domain is impaired, but it may be useful for monitoring cognition over time in clinical practice.

Key findings

  • The DSST is sensitive to cognitive impairment and change across psychiatric, neurologic, pharmacologic, and sleep-related conditions; in MDD, a meta-analysis of 1904 subjects across 22 studies found moderate impairment versus controls (Cohen’s d = 0.55; 95% CI, 0.34–0.75; P < 0.001).
  • Vortioxetine trials in MDD reported DSST treatment effect sizes of 0.51 and 0.52 for 10 or 20 mg in one study and 0.254 for 10 to 20 mg in another; a meta-analysis found vortioxetine improved DSST-assessed cognition more than other antidepressants.
  • DSST performance correlates with real-world functional outcomes: in MDD patients 6 months after hospital discharge, DSST was strongly associated with functional recovery in work, school, and housing (odds ratio nearly 20).
  • The DSST is polyfactorial and sensitive but not specific: impaired performance can arise from motor speed, attention, visuoperceptual functions, associative learning, working memory, and executive functions, so it does not by itself identify the affected cognitive domain.

Methods

  • Narrative review of specific studies and articles to illustrate what the DSST measures, its sensitivity to change, and its use in clinical practice.
  • Evidence reviewed includes DSST studies in brain damage, schizophrenia, MDD, diabetes, sleep restriction, alcohol intoxication, and sedative/hypnotic pharmacodynamic studies.
  • Main synthesis compares DSST effect sizes across patient groups and pharmacologic benchmarks, including alcohol, antihistamines, benzodiazepines, caffeine, and sleep deprivation.

Limitations

  • The paper states the DSST has low specificity for determining exactly which cognitive domain has been affected and raises the question of whether a single brief cognitive assessment can be sufficient for clinically meaningful conclusions.
  • The paper notes that repeated DSST administration may produce learning or practice effects, although randomized designs can overcome resulting confounding in some studies.
  • Evident from the text: this is a narrative review of selected studies rather than a systematic review, and it does not report a formal search strategy, inclusion criteria, or quantitative synthesis of all available DSST evidence.

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Integrity signals

Registry

Crossref · 10.1097/jcp.0000000000000941

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

FIGURE 1 The DSST symbol coding sheet. Figure reprinted from Patel and Kurdi.3
FIGURE 1 The DSST symbol coding sheet. Figure reprinted from Patel and Kurdi.3CC BY-NC-ND · PubMed Central
FIGURE 2 Alcohol has known effects on DSST performance; this observation can be used as a benchmark to reference the recovery time following administration of sedating agents. Graph shows effects over time following 2 mg/70 kg midazolam (square), 70 mg/70 kg propofol (circle), and 50 μg/70 kg fentanyl (triangle) on the DSST performance relative to placebo (diamond) and relative to the effect of sustained BAC levels of approximately 0.11%. The alcohol effects are denoted in the gray area (mean: center line; outermost lines: ±1 SEM). Closed symbols represent statistically significant differences from placebo at a given time. Figure reprinted from Thapar et al.33 Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer. Please contact permissions@lww.com for further information.
FIGURE 2 Alcohol has known effects on DSST performance; this observation can be used as a benchmark to reference the recovery time following administration of sedating agents. Graph shows effects over time following 2 mg/70 kg midazolam (square), 70 mg/70 kg propofol (circle), and 50 μg/70 kg fentanyl (triangle) on the DSST performance relative to placebo (diamond) and relative to the effect of sustained BAC levels of approximately 0.11%. The alcohol effects are denoted in the gray area (mean: center line; outermost lines: ±1 SEM). Closed symbols represent statistically significant differences from placebo at a given time. Figure reprinted from Thapar et al.33 Promotional and commercial use of the material in print, digital or mobile device format is prohibited without the permission from the publisher Wolters Kluwer. Please contact permissions@lww.com for further information.CC BY-NC-ND · PubMed Central
FIGURE 3 The chronic sleep restriction experiment involved randomization to 1 of 3 sleep doses (4-, 6-, or 8-hour time in bed per night), which were maintained for 14 consecutive days. Subjects were tested every 2 hours each day; data points represent the daily average (7:30 am–11:30 pm) expressed relative to baseline. The study also involved 3 baseline (predeprivation) days and 3 recovery days.37 Figure republished with permission of the Journal of Sleep Medicine from Banks S, Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med. 2007;3:519–528; permission conveyed through Copyright Clearance Center, Inc. TIB indicates time in bed.
FIGURE 3 The chronic sleep restriction experiment involved randomization to 1 of 3 sleep doses (4-, 6-, or 8-hour time in bed per night), which were maintained for 14 consecutive days. Subjects were tested every 2 hours each day; data points represent the daily average (7:30 am–11:30 pm) expressed relative to baseline. The study also involved 3 baseline (predeprivation) days and 3 recovery days.37 Figure republished with permission of the Journal of Sleep Medicine from Banks S, Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med. 2007;3:519–528; permission conveyed through Copyright Clearance Center, Inc. TIB indicates time in bed.CC BY-NC-ND · PubMed Central
FIGURE 4 Effect size on DSST performance of antidepressants in patients with MDD is compared with the effect size in healthy volunteers for known compounds such as acute caffeine consumption, caffeine deprivation, and diphenhydramine (an antihistamine). Benchmarking effect sizes to known compounds in clinically healthy volunteers serves as a guide to evaluating the clinical meaningfulness of particular effect sizes in cognition.32,39,43,44,48–53 Positive effect sizes indicate improvements in cognitive functioning, and negative effect sizes indicate decline in cognitive functioning. The top part of the graph shows the effects of antidepressant treatments on cognitive functioning, whereas the bottom part illustrates the effects of other agents known to affect cognitive functioning in healthy volunteers. Figure 4 can be viewed online in color at www.psychopharmacology.com.
FIGURE 4 Effect size on DSST performance of antidepressants in patients with MDD is compared with the effect size in healthy volunteers for known compounds such as acute caffeine consumption, caffeine deprivation, and diphenhydramine (an antihistamine). Benchmarking effect sizes to known compounds in clinically healthy volunteers serves as a guide to evaluating the clinical meaningfulness of particular effect sizes in cognition.32,39,43,44,48–53 Positive effect sizes indicate improvements in cognitive functioning, and negative effect sizes indicate decline in cognitive functioning. The top part of the graph shows the effects of antidepressant treatments on cognitive functioning, whereas the bottom part illustrates the effects of other agents known to affect cognitive functioning in healthy volunteers. Figure 4 can be viewed online in color at www.psychopharmacology.com.CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

39 Not checked yet · 28 Own interpretation · 11 Sources not found · 2 No basis given · 1 Own method

Verify all 43 references — free account
  • It may state two separate claims as one. 14
  • Probably not a substantial claim. 16
27 of 27
  • The paper relies on this without support.

    In clinical practice, the DSST is administered in the manner in which it was validated.

    “the validity and reliability of the paper DSST depend on the test being administered in the manner it was validated.”
  • The authors state this as an assumption.

    Cognition is important for functioning and quality of life.

    “Although the importance of cognition for functioning and quality of life may be regarded as self-evident”
2 of 2

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Metadata

Authors
Jaeger, J.
Affiliations
Albert Einstein College of Medicine (US)
Corresponding author
Jaeger, Judith
Venue
Journal of Clinical Psychopharmacology
Published
2018-10
Volume
38
Issue
5
Pages
513-519
ISSN
  • 0271-0749 (ISSN-L)
  • 1533-712X
OpenAlex
W2888254436
Cited by
836
References
51
Citations by year
2026: 103 · 2025: 169 · 2024: 175 · 2023: 119 · 2022: 100 · 2021: 100 · 2020: 52 · 2019: 17
FWCI
5.73
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Psychopharmacology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Psychology › Applied Psychology › Psychological Testing and Assessment
  • Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
Digit Symbol Substitution Test, cognitive impairment, neuropsychological assessment, major depressive disorder, schizophrenia, treatment monitoring, functional disability, sensitivity to change, associative learning, clinical decision-making
MeSH terms
Association Learning, Major Depressive Disorder, Humans, Neuropsychological Tests, Reproducibility of Results, Cognitive Dysfunction

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