Evidence map›Paper›PMID 40759531›Full record

ArticlePsychological medicine2025

Genetic overlap between functional impairment and depression and anxiety symptom severity: evidence from the GLAD Study.

Megan Skelton, Jessica Mundy, Abigail R Ter Kuile, Brett N Adey, Chérie Armour, Joshua E J Buckman, Jonathan R I Coleman, Molly R Davies, Colette R Hirsch, Matthew Hotopf and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Anxiety disorders: a cross-sectional study of clinical and biological associations.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Article
  3. Article
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

26 authors.

Megan SkeltonInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-7619-349X
Jessica MundyInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0001-5513-8902
Abigail R Ter KuileInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-7869-3754
Brett N AdeyInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-4356-4079
Chérie ArmourResearch Centre for Stress, Trauma & Related Conditions (STARC), School of Psychology, Queen's University Belfast, Belfast, Northern Ireland, UK.ORCID 0000-0001-7649-3874
Joshua E J BuckmanCentre for Outcomes Research and Effectiveness (CORE), Research Department of Clinical, Educational and Health Psychology, University College London, London, UK.ORCID 0000-0002-2281-0907
Jonathan R I ColemanInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-6759-0944
Molly R DaviesInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-3483-9907
Colette R HirschInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-3579-2418
Matthew HotopfInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-3980-4466
Ian R JonesNational Centre for Mental Health, Division of Psychiatry and Clinical Neuroscience, Cardiff University, Cardiff, UK.ORCID 0000-0001-5821-5889
Gursharan KalsiInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-5156-7176
Georgina KrebsInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-5353-5645
Sang Hyuck LeeInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-5610-033X
Yuhao LinInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Andrew M McIntoshDivision of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-0198-4588
Alicia J PeelInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-6144-5412
Christopher RaynerInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2950-343X
Katharine A RimesInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2634-455X
Daniel J SmithDivision of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-2267-1951
Katherine N ThompsonInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-1818-0428
David VealeInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-1717-4766
James T R WaltersNational Centre for Mental Health, Division of Psychiatry and Clinical Neuroscience, Cardiff University, Cardiff, UK.ORCID 0000-0002-6980-4053
Christopher HübelInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0002-1267-8287
Gerome BreenInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0003-2053-1792
Thalia C EleyInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.ORCID 0000-0001-6458-0700

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFunctional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.

methodsIn 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.

resultsThe phenotypic correlations were moderate across the three measures (Pearson's

conclusionsAmong individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.

Indexed as

Activities of Daily LivingAnxietyAnxiety DisordersDepressionMajor Depressive DisorderAdultFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideSeverity of Illness Indexdimensional symptomsdisabilitygenetic correlationsGWASinternalizing symptomsmental health

Identifiers

PMID40759531
PMCPMC12341029

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