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Cited by 340Attention Deficit Hyperactivity DisorderChild and Adolescent Psychosocial and Emotional DevelopmentAutism Spectrum Disorder Research

Subtyping Attention-Deficit/Hyperactivity Disorder Using Temperament Dimensions: Toward Biologically Based Nosologic Criteria

Open access
Karalunas, Sarah L., Fair, Damien, Musser, Erica D., Aykes, Kamari, Iyer, Swathi P., Nigg, Joel T.·2014·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2014.763PMC PMC4278404
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Abstract

IMPORTANCE: Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (i.e., temperament), novel classification algorithms, and multiple external validators. DESIGN, SETTING, AND PARTICIPANTS: A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. MAIN OUTCOMES AND MEASURES: Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). RESULTS: The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing clinical demarcations including DSM-5 presentations or symptom severity. These types showed stability over time and were distinguished by unique patterns of cardiac physiological response, resting-state functional brain connectivity, and clinical outcomes 1 year later. CONCLUSIONS AND RELEVANCE: Results suggest that a biologically informed temperament-based typology, developed with a discovery-based community detection algorithm, provides a superior description of heterogeneity in the ADHD population than does any current clinical nosologic criteria. This demonstration sets the stage for more aggressive attempts at a tractable, biologically based nosology.

AI snapshot

Written from the paper’s full text.

TL;DR

This study used parent-rated temperament and community detection to identify three ADHD subgroups—Mild, Surgent, and Irritable—that cut across DSM-5 presentations. The subgroups showed distinct peripheral physiology, amygdala resting-state connectivity, one-year stability, and prediction of new comorbid disorders.

Key findings

  • Among 247 children with ADHD, community detection produced three temperament-based types: Mild (n=64, 25.9%), Surgent (n=85, 34.4%), and Irritable (n=98, 39.7%), with strong separation (Q=.50); these types did not map onto DSM-5 ADHD presentations.
  • Surgent children had shorter tonic pre-ejection period than controls and the other ADHD types (baseline F[1,305]=2.73, p=.044; task F[3,303]=3.95, p=.009), while Irritable children showed a smaller respiratory sinus arrhythmia increase during negative emotion conditions, and Surgent children showed respiratory sinus arrhythmia withdrawal during positive conditions.
  • Amygdala connectivity differed by type: Irritable children had weaker amygdala–anterior insula connectivity than all other groups, Mild children had reduced posterior cingulate/precuneus connectivity, and Surgent children had increased amygdala–cingulate/precuneus connectivity relative to Mild and Irritable children.
  • At one-year follow-up, types were more stable than chance (χ²[4]=71.84, p<.001); over 70% of Surgent and Irritable children stayed in the same type, whereas only 43.6% of Mild children did. Irritable children had more new comorbid disorder onsets (39.5%) than controls (11.1%), Mild (18.2%), or Surgent (11.1%) children, and temperament type predicted comorbidity onset (p=.019, OR=2.46) while DSM-5 presentation and ODD symptoms did not uniquely predict it.

Methods

  • Longitudinal community-recruited sample of 437 children ages 7–11: 190 controls (46.3% male) and 247 with ADHD (71.6% male). Parent/guardian ratings on the Temperament in Middle Childhood Questionnaire provided 16 subscales used as clustering features.
  • Community detection used a weight-conserving modularity algorithm on child-by-child correlations; final assignments were based on the modal group across 10 runs, with Variation of Information used to assess robustness.
  • External validation included peripheral physiology (respiratory sinus arrhythmia and pre-ejection period) during emotion tasks for 178 ADHD and 128 control children, resting-state functional connectivity MRI with an amygdala seed for 39 ADHD children (18 Mild, 11 Surgent, 10 Irritable) and 15 controls, and one-year follow-up for 101 children with ADHD. Analyses included repeated-measures ANOVAs, connectivity t-tests with Monte Carlo correction, and logistic/multinomial regression.

Limitations

  • The paper states that imaging results come from a small subsample and should be considered preliminary; it also notes known limitations of parent-report measures and calls for future work on family history, genetics, replication in other samples, and treatment response.
  • The paper states that the Mild type was less well validated because it showed normative peripheral physiology and was not particularly stable over time.
  • Evident from the text: community detection is nondeterministic, so the authors relied on modal assignments across 10 runs; the follow-up sample was only 101 children with ADHD, and the MRI subsample was small, limiting confidence in neural findings.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jamapsychiatry.2014.763This paper is marked retracted.

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 55 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The Surgent type differed from the other three groups during the negative suppression condition (p=.036, η2=0.04) because they showed no change in RSA in this condition from baseline.

    “The Surgent Type differed from the other three groups during the negative suppression condition (p=.036, η2=0.04) because they showed no change in RSA in this condition from baseline.”
    Quote in the paperSubstantial claim
  • Findingown data

    Type 1 had milder impulsivity, inhibition, and attentional dyscontrol than the other two ADHD types.

    “Type 1 had milder impulsivity, inhibition, and attentional dyscontrol than the other two ADHD types (all p<.001).”
    Quote in the paperSubstantial claim
  • Findingown data

    For tonic PEP scores across the four emotion task conditions, only the group main effect was significant (F[3,303]=3.95, p=.009, η2=0.05).

    “Only the group main effect was significant (F[3, 303]=3.95, p=.009, η2=0.05).”
    Quote in the paperSubstantial claim
  • Findingown data

    Community detection on the 247 children with ADHD yielded a modal solution of three profiles with n=64 (25.9%), 85 (34.4%), and 98 (39.7%).

    “Community detection using the 247 children with ADHD identified as the modal solution three profiles (referred to herein as “types”) with n= 64 (25.9%), 85 (34.4%), and 98 (39.7%) based on modal type assignments.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The TMCQ subscales and higher order factors are influenced by underlying neurobehavioral systems.
  • Findingown data

    The Surgent group had significantly shorter PEP values than typically-developing children or the other ADHD types.

    “Post-hoc tests indicated that the Surgent group had significantly shorter PEP values than typically-developing children or the other ADHD types.”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingown data

    Community detection applied to all 437 children identified three profiles with sizes 192, 181, and 64 and a quality quotient of .55.

    “At the first step, including all 437 children in the sample, community detection identified three profiles of children (Q=.55) with sizes of 192, 181, 64.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Type 3 (Irritable ADHD) had greater impulsivity and attentional dyscontrol than Mild type and more negative emotionality than other two types or controls.

    “Type 3, in addition to greater impulsivity and attentional dyscontrol than the Mild type, also had more negative emotionality than the other two types or the controls (all p<.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was a main effect of group on RSA change from baseline to task (F[3,303]=3.97, p=.047, η2=0.03), qualified by a three-way Valence×Condition×Group interaction (F[3,303]=4.09, p=.018, η2=0.03).

    “A main effect of group (F[3, 303]=3.97, p=.047, η2=0.03) was qualified by a 3-way interaction of Valence×Condition × Group (F[3, 303]=4.09, p=.018, η2=0.03).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The first profile contained 82% of control children and 13% of ADHD children, while profiles 2 and 3 together contained 87% of ADHD children and 18% of non-ADHD controls.

    “Profile 1 included 82% of the control children and only 13% of the ADHD children. Profiles 2 and 3 together included 87% of the ADHD children and only 18% of non-ADHD controls.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Type 3 had higher levels of anger, discomfort, fear, and sadness, and lower soothability than other types and controls.

    “This included higher levels of anger, discomfort, fear, and sadness, and lower levels of soothability (all p<.001), suggesting this is a group of children prone to anger, tantrums, and irritable behavior as described in recent literature [53].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Leibenluft E Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths The American Journal of Psychiatry 2011 168 2 129 21123313 PMC3396206

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    None of the groups showed significant change in PEP from baseline to task, and PEP reactivity scores did not differ from zero (all p>.05).

    “None of the groups showed significant change in PEP from baseline to task (i.e. PEP reactivity scores did not differ from zero, all p>.05), and there were no significant main or interaction effects when PEP reactivity scores were examined for the emotion task (all p>.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Type 2 (Surgent ADHD) had more severe impulsivity than Type 1 and less shyness and more assertiveness/dominance, high-intensity pleasure seeking, and activity level than either other type or controls.

    “Type 2 had more severe impulsivity than Type 1, and also less shyness and more assertiveness/dominance, high-intensity pleasure seeking, and activity level than either of the other two types or than controls (all p<.001); we labeled this type “Surgent ADHD.””
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Type 1 (Mild ADHD) was more impulsive and inattentive than controls and less affiliative, but otherwise did not differ from controls on any temperament domain.

    “Clinically, Type 1 was more impulsive and inattentive (all p<.01) than controls, as well as less affiliative (all p<.05), but otherwise did not differ from controls on any temperament domain.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Mild type often changed profile: 43.6% remained Mild at Time 2; 41% became Surgent and 15.4% became Irritable.

    “In contrast, the Mild type often changed profile: 43.6% remained Mild type at Time 2; 41% became Surgent type and 15.4% became Irritable type (see eVideo 1 in Supplement for depiction of stability of types over time).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The one-year follow-up period is sufficient to assess stability and clinical prediction.

  • May combine two claims.

    Findingown data

    Neither DSM-5 presentations nor groups based on presence/absence of ODD symptoms differed in rates of new comorbid disorder onsets at Time 2 (χ2[1]=0.68, p=.409 and χ2[1]=2.54, p=.111, respectively).

    “neither DSM-5 presentations nor groups based on the presence/absence of ODD symptoms (i.e. 0 symptoms versus 1+ symptoms) differed in their rates of new comorbid disorder onsets at Time 2 (χ2[1]=0.68, p=.409 and χ2[1]=2.54, p=.111, respectively).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither presence of Time 1 ODD symptoms (p=.563) nor ADHD DSM-5 presentation (p=.113) uniquely predicted new onsets at Time 2.

    “Neither the presence of Time 1 ODD symptoms (p=.563) nor ADHD DSM-5 presentation (p=.113) uniquely predicted new onsets at Time 2.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Irritable group displayed weaker connectivity from the amygdala to the anterior insula relative to all other groups and weaker connectivity to the posterior cingulate relative to typically-developing and Surgent children.

    “The Irritable group displayed weaker connectivity (in the form of reduced negative relationships) from the amygdala to the anterior insula relative to all other groups (including non-ADHD controls) and weaker connectivity to the posterior cingulate (a key hub in the default network) relative to typically-developing and the Surgent children.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Surgent type evidenced increased connectivity from the amygdala to cingulate/precuneus compared to Mild and Irritable groups, but was similar relative to control populations.

    “The Surgent type evidenced increased connectivity from the amygdala to cingulate/precuneus compared to the Mild and Irritable groups, but was similar relative to control populations.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The Surgent and Irritable types were stable over time.

    “the subgroups found here were largely stable over time”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The Surgent and Irritable types have distinct peripheral physiological profiles compared to each other and to typically-developing children.

    “Thus, data suggest that the Surgent and Irritable types have distinct peripheral physiological profiles as compared to each other and to typically-developing children.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The reliabilities of TMCQ scales in the current sample were all satisfactory.

    “List of scales and reliabilities in the current sample (which were all satisfactory) are provided in the Supplement.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The amygdala plays a key role in emotion and motivation and is an important brain correlate of temperament domains.

    “The amygdala, in particular, plays a key role in emotion and motivation, and so is one important brain correlate of temperament domains [17, 28, 29].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] Smillie LD Extraversion and Reward Processing Current Directions in Psychological Science 2013 22 3 167 172 PMC3989147 24748727

      Not checked in the free run.

    • cites [28] Miskovic V Schmidt LA New directions in the study of individual differences in temperament: A brain–body approach to understanding fearful and fearless children Monographs of the Society for Research in Child Development 2012 77 2 28 38

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    • cites [29] Rothbart MK Temperament, development, and personality Current Directions in Psychological Science 2007 16 4 207 212

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Standard methods for artifact detection were followed as published in prior work.

    “Standard methods for artifact detection were followed as published in our prior work [40] and are also provided in the Supplement.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Musser ED Emotion regulation via the autonomic nervous system in children with attention-deficit/hyperactivity disorder (ADHD) Journal of Abnormal Child Psychology: An official publication of the International Society for Research in Child and Adolescent Psychopathology 2011 39 6 841 852 PMC3112468 21394506

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DSM-IV subtypes (and thus DSM-5 presentations) fail to elucidate clear differences in pathophysiology or clinical course, in part due to their instability over time.

    “but DSM-IV subtypes (and thus DSM-5 presentations) fail to elucidate clear differences in pathophysiology or clinical course, in part due to their own instability over time [5, 7–9].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [5] Khan SA Faraone SV The genetics of ADHD: a literature review of 2005 Current Psychiatry Reports 2006 8 5 393 16968622

      Not checked in the free run.

    • cites [7] Chhabildas N Pennington BF Willcutt EG A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD Journal of Abnormal Child Psychology 2001 29 6 529 540 11761286

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    • cites [8] Lahey BB Pelham WE Loney J Lee SS Willcutt E Instability of the DSM-IV subtypes of ADHD from preschool through elementary school Archives of General Psychiatry 2005 62 8 896 902 16061767

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    • cites [9] Willcutt EG Validity of DSM–IV Attention Deficit/Hyperactivity Disorder Symptom Dimensions and Subtypes 2012 PMC3622557 22612200

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  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Thresholding based on Monte Carlo simulation was implemented to account for multiple comparisons.

    “To account for multiple comparisons, thresholding based on Monte Carlo simulation was implemented [52].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Forman SD Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold Magnetic Resonance in Medicine 1995 33 5 636 647 7596267

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    A secondary validation method (VOI) was used to evaluate internal validity (group robustness to chance data variation).

    “A secondary validation method [Variation of Information Algorithm (VOI), 37] was also used to evaluate internal validity (group robustness to chance data variation).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Karrer B Levina E Newman ME Robustness of community structure in networks Physical Review E 2008 77 4 046119 18517702

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Community detection is a widely used optimization clustering method that is data-driven and provides a quantitative measure of group robustness to chance variations.

    “Community detection is a widely used optimization clustering method (another well-known optimization clustering method is mixture modeling). As a clustering approach it has the attractive features of being data-driven (in that the number of communities does not have to be pre-specified in the model) and provides a quantitative measure of group robustness to chance variations in the data structure.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Newman MEJ Modularity and community structure in networks Proceedings of the National Academy of Sciences of the United States of America 2006 103 23 8577 8582 16723398 PMC1482622

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Temperament traits have distinct neurobiological correlates with a substantial literature in humans and animals.

    “Temperament traits also have distinct neurobiological correlates with a substantial literature in humans and animals [18–20].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] Depue RA Lenzenweger MF A neurobehavioral dimensional model of personality disturbance Major theories of personality disorder 2005 2 391 453

      Not checked in the free run.

    • cites [19] Kennis M Rademaker AR Geuze E Neural correlates of personality: An integrative review Neuroscience & Biobehavioral Reviews 2012 23142157

      Not checked in the free run.

    • cites [20] Zuckerman M Psychobiology of personality 2005 2nd ed. New York, NY Cambridge University Press

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Motion was corrected and quantified several ways.

    “Motion, a known confound in functional MRI studies, was corrected and quantified several ways [46, 49] (for details see the Supplement).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46] Fair DA Distinct neural signatures detected for ADHD subtypes after controlling for micro-movements in resting state functional connectivity MRI data Frontiers in Systems Neuroscience 2012 6 PMC3563110 23382713

      Not checked in the free run.

    • cites [49] Power JD Barnes KA Snyder AZ Schlaggar BL Petersen SE Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion Neuroimage 2012 59 3 2142 2154 22019881 PMC3254728

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Clustering algorithms can yield varying results depending on algorithm and features, and are exploratory.

    “Clustering algorithms can be expected to yield varying results depending on the algorithm used and features selected as input [13] and therefore are, in themselves, exploratory [14]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] Everitt BS Landau S Leese M Stahl D Cluster Analysis 2011 5th ed. West Sussex, United Kingdom John Wiley & Sons, Ltd

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    • cites [14] Jain AK Data clustering: 50 years beyond K-means Pattern Recognition Letters 2010 31 8 651 666

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  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Final group assignments were based on the modal group assignment across 10 runs of the modularity algorithm to generate a single stable depiction of structure.

    “To generate a single, stable depiction of structure, final group assignments for each child were based on the modal group assignment across 10 runs of the modularity algorithm.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In humans, temperament domains are differentially related to peripheral nervous system indicators and to specific neural circuitry.

    “In humans, temperament domains are differentially related to peripheral nervous system indicators [21–25], as well to specific neural circuitry [e.g. amygdala, hippocampus, insula, and striatum, anterior cingulate cortex, and prefrontal cortex, 26, 27].”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [21] Beauchaine TP Katkin ES Strassberg Z Snarr J Disinhibitory psychopathology in male adolescents: Discriminating conduct disorder from attention-deficit/hyperactivity disorder through concurrent assessment of multiple autonomic states Journal of Abnormal Psychology 2001 110 4 610 624 11727950

      Not checked in the free run.

    • cites [22] Healy B Treadwell A Reagan M Measures of RSA suppression, attentional control, and negative affect predict self-ratings of executive functions Journal of Psychophysiology 2011 25 4 164 173

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    • cites [23] Miller JG Children's dynamic RSA change during anger and its relations with parenting, temperament, and control of aggression Biological Psychology 2012 PMC4055035 23274169

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    • cites [24] Stifter CA Dollar JM Cipriano EA Temperament and emotion regulation: the role of autonomic nervous system reactivity Developmental psychobiology 2011 53 3 266 279 21400489 PMC3737744

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    • cites [25] Zalewski M Lengua LJ Wilson AC Trancik A Bazinet A Emotion regulation profiles, temperament, and adjustment problems in preadolescents Child Development 2011 82 3 951 966 21413935 PMC4080917

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    • cites [26] Ochsner KN Silvers JA Buhle JT Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion Annals of the New York Academy of Sciences 2012 1251 1 E1 E24 23025352 PMC4133790

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    • cites [27] Whittle S Allen NB Lubman DI Yücel M The neurobiological basis of temperament: Towards a better understanding of psychopathology Neuroscience & Biobehavioral Reviews 2006 30 4 511 525 16289282

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    Functional images were processed to reduce artifacts and connectivity was processed following published methods.

    “Functional images were processed to reduce artifacts and connectivity was processed following published methods [48] and are reproduced in the Supplement.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Miezin FM Maccotta L Ollinger J Petersen S Buckner R Characterizing the hemodynamic response: effects of presentation rate, sampling procedure, and the possibility of ordering brain activity based on relative timing Neuroimage 2000 11 6 735 759 10860799

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The imaging findings come from a small subsample and are preliminary.

    “imaging results are based on a small subsample of participants and should be considered preliminary”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The data suggest the insula matters for emotional regulation and impulse control.

    “Together these data may highlight the region’s importance for emotional regulation and impulse control.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The insula is important for monitoring and adjusting sympathetic and parasympathetic tone.

  • Classified as probably not a substantial claim.

    Premisenone given

    Modularity algorithms are not deterministic and can yield slightly different solutions on different runs.

    “Importantly, this and other modularity algorithms are not deterministic, and thus can yield slightly different solutions on different runs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The Surgent and Irritable types are promising, novel ADHD types.

    “they emerge as promising, novel types of ADHD”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Temperament traits have been studied in numerous other disorders.

    “temperament traits have been investigated in many other disorders [65]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Nigg JT Temperament and developmental psychopathology Journal of Child Psychology and Psychiatry 2006 47 3–4 395 422 16492265

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The findings largely align with and extend earlier temperament-subgroup work in a separate ADHD sample.

    “while being mostly consistent with and building on previous work exploring temperament subgroups in ADHD in a different sample [66]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Martel MM Goth-Owens T Martinez-Torteya C Nigg JT A person-centered personality approach to heterogeneity in attention-deficit/hyperactivity disorder (ADHD) Journal of Abnormal Psychology 2010 119 1 186 196 20141255 PMC2846424

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Revising ADHD nosology is feasible and biologically meaningful.

    “Results suggest that revising the nosology in the case of ADHD is tractable and will be biologically meaningful.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Parent-reported temperament measures have some validity and clinical applicability.

    “suggesting some validity and clinical applicability for these measures”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The findings largely agree with the prior ADHD temperament theory that motivated the study, though they imply some changes.

    “these findings are broadly consistent with, but suggest some modifications to, prior theory of ADHD temperament variation that inspired this work [64, 65]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [64] Nigg J Goldsmith HH Sachek J Temperament and Attention Deficit Hyperactivity Disorder: The Development of a Multiple Pathway Model Journal of Clinical Child and Adolescent Psychology 2004 33 1 42 53 15028540

      Not checked in the free run.

    • cites [65] Nigg JT Temperament and developmental psychopathology Journal of Child Psychology and Psychiatry 2006 47 3–4 395 422 16492265

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The insula is implicated in higher order control processing.

    “it has also been shown to be heavily involved in higher order control processing [62, 63]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [62] Dosenbach NU Fair DA Cohen AL Schlaggar BL Petersen SE A dual-networks architecture of top-down control Trends in Cognitive Sciences 2008 12 3 99 105 18262825 PMC3632449

      Not checked in the free run.

    • cites [63] Dosenbach NU Distinct brain networks for adaptive and stable task control in humans Proceedings of the National Academy of Sciences 2007 104 26 11073 11078 PMC1904171 17576922

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The TMCQ is a widely used parent-rated measure of child temperament.

    “A parent/guardian completed the widely used Temperament in Middle Childhood Questionnaire [TMCQ, 34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Simonds J Rothbart MK The Temperament in Middle Childhood Questionnaire (TMCQ): A computerized self-report measure of temperament for ages 7–10, in Occasional Temperament Conference 2004 Athens, GA

      Not checked in the free run.

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  • The paper relies on this without support.

    No prior study of alternative nosology has demonstrated both biological validity and clinical prediction within the same sample.

    “For example, no study of alternative nosology has demonstrated both biological validity and clinical prediction within the same sample.”

  • The authors state this as an assumption.

    The TMCQ subscales and higher order factors are influenced by underlying neurobehavioral systems.

    “Items form 16 subscales and three higher order factors that are hypothesized to be influenced by underlying neurobehavioral systems.”

  • The paper relies on this without support.

    The 247 children with ADHD in this community-recruited sample are representative of the broader ADHD population.

    “Data are reported for 437 children: NControl=190 (46.3% male); NADHD=247 (71.6% male) between the ages of 7–11. Participants were drawn from the Oregon ADHD Program, a child cohort for which the community-based recruitment and enrollment procedures and multi-informant assessment procedures for ADHD diagnosis are published elsewhere [31–33] and described in the Supplement.”

  • The paper relies on this without support.

    The one-year follow-up period is sufficient to assess stability and clinical prediction.

    “One-year longitudinal follow-up data on clinical features and TMCQ ratings are reported for 101 children with ADHD (98% of those currently due for follow up in this ongoing study).”

  • The paper relies on this without support.

    Parent-report on the TMCQ broadly captures RDoC domains of negative valence systems, positive valence systems/approach motivation, and cognitive control.

    “parent-report on the TMCQ broadly captures RDoC domains of negative valence systems, positive valence systems/approach motivation, and cognitive control”

  • The paper relies on this without support.

    The insula is important for monitoring and adjusting sympathetic and parasympathetic tone.

    “the insula is a region that has been long known to be important for monitoring and adjusting sympathetic and parasympathetic tone”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Limited sample size, clinical heterogeneity in terms of comorbidities, gender effects, diverse courses and outcomes, and varying etiological sources also play roles in the inconsistency of existing studies in ADHD.

    “Limited sample size, clinical heterogeneity in terms of comorbidities, gender effects, diverse courses and outcomes, varying etiological sources, also play their roles (Hyman, 2007; Kapur et al., 2012; Karalunas et al., 2014).”

    From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Karalunas et al., 2014

    The Introduction (page not provided) describes suspected diverse etiologies in ADHD and limitations of existing subtypes in distinguishing clinical course. The Results on longitudinal outcomes (page not provided) also document differences in new comorbid disorders. The paper does not establish that limited sample sizes or gender effects cause inconsistency across ADHD studies, so the full list of explanations is not supported by this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Discovery methods applied to temperamental traits identified ADHD subtypes marked by high positive and negative emotionality.

    “discovery methods applied to temperamental traits distinguished ADHD subtypes defined by high positive and negative emotionality (Karalunas et al., 2014).”

    From Data‐driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders (2020) · cites this paper as Karalunas et al., 2014

  • Community detection on temperamental traits in ADHD revealed segregation by positive and negative emotion regulation problems.

    “Interestingly, community detection applied to temperamental traits in ADHD, revealed segregation by positive and negative emotion regulation problems (Karalunas et al., 2014)”

    From Data‐driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders (2020) · cites this paper as Karalunas et al., 2014

  • Attempts to group mental disorders by biological substrates have been made, but more research is required to establish meaningful links to behaviors, developmental course, or treatment.

    “Attempts to group mental disorders by biological substrates have been made (Hyman 2010, Karalunas et al. 2014), but more research is required to establish meaningful links to behaviors, developmental course, or treatment (Sisti et al. 2013).”

    From Recent Advances in Autism Research as Reflected in DSM-5 Criteria for Autism Spectrum Disorder (2015) · cites this paper as Karalunas et al. 2014

  • The findings here are not that dissimilar with other modeling approaches such as latent class analysis that often derive low and high performing groups.

    “The findings here are not that dissimilar with other modeling approaches such as latent class analysis that often derive low and high performing groups ( Karalunas et al., 2014, Katuwal et al., 2016).”

    From Heterogeneity of executive function revealed by a functional random forest approach across ADHD and ASD (2020) · cites this paper as Karalunas et al., 2014

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Baseline PEP group test has the wrong numerator degrees of freedom

    Minor

    The analysis compares four groups, so an omnibus group effect has 3 numerator degrees of freedom, not the reported 1. The reported F statistic and p-value therefore do not describe a consistent four-group test.

    Reported 1 · recomputed 3

  • First profile's size conflicts with its reported composition

    Minor

    With 190 controls and 247 children with ADHD, the stated percentages put approximately 156 controls and 32 children with ADHD in Profile 1, or about 188 children total-not 192. Rounding the percentages to whole numbers cannot account for the gap.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. [15]Bates JE Goodnight JA Fite JE Lewis M Haviland-Jones JM Barrett LF Temperament and Emotion, in Handbook of Emotion 2008 New York, NY The Guilford Press
  2. [20]Zuckerman M Psychobiology of personality 2005 2nd ed. New York, NY Cambridge University Press
  3. [34]Simonds J Rothbart MK The Temperament in Middle Childhood Questionnaire (TMCQ): A computerized self-report measure of temperament for ages 7–10, in Occasional Temperament Conference 2004 Athens, GA
  4. [50]Patenaude B Smith S Kennedy D Jenkinson M FIRST-FMRIB’s integrated registration and segmentation tool Human Brain Mapping Conference 2007
  5. [55]Keppel G Review of Statistical Analysis in Psychology and Education PsycCRITIQUES 1981 26 9 5th ed. 723 723

Cited by

Sorted by citations

Related

Authors
Karalunas, S. L., Fair, D., Musser, E. D., Aykes, K., Iyer, S. P., & Nigg, J. T.
Affiliations
  • Oregon Health & Science University (US)
  • Florida International University (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Karalunas, Sarah L.
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2014-09-01
Volume
71
Issue
9
Pages
1015
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2014.763
PMC
PMC4278404
OpenAlex
W1983915852
Semantic Scholar
15a19b0e1e4cfa79179c3b4e696bd06c7c77fc40
Cited by
340
References
71
Citations by year
2026: 16 · 2025: 15 · 2024: 18 · 2023: 17 · 2022: 29 · 2021: 37 · 2020: 39 · 2019: 37 · 2018: 26 · 2017: 41 · 2016: 32 · 2015: 29 · 2014: 4
FWCI
26.96
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2018-03-07)
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01mh099064-05)
  • National Institute of Mental Health (R01-MH099064, R01MH115357, F32MH098632, R00MH091238, R37MH059105, R01MH096773, R01MH059105, R01MH086654)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
attention deficit hyperactivity disorder, childhood ADHD, temperament dimensions, Research Domain Criteria, community detection, emotion regulation, approach motivation, negative affectivity, pre-ejection period, resting-state functional connectivity, disease classification, clinical prediction, longitudinal stability
MeSH terms
Algorithms, Attention Deficit Disorder with Hyperactivity, Brain, Child, Electrocardiography, Female, Heart Rate, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Surveys and Questionnaires, Temperament, Case-Control Studies, Functional Neuroimaging, Respiratory Sinus Arrhythmia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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