Skip to main content Accessibility help
×
Home

A risk calculator to predict adult attention-deficit/hyperactivity disorder: generation and external validation in three birth cohorts and one clinical sample

  • A. Caye (a1), J. Agnew-Blais (a2), L. Arseneault (a2), H. Gonçalves (a3), C. Kieling (a1), K. Langley (a4) (a5), A. M. B. Menezes (a3), T. E. Moffitt (a6), I. C. Passos (a7), T. B. Rocha (a1), M. H. Sibley (a8), J. M. Swanson (a9), A. Thapar (a5), F. Wehrmeister (a3) and L. A. Rohde (a1) (a10)...
  • Please note a correction has been issued for this article.

Abstract

Aim

Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD).

Methods

Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC – UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old).

Results

The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79–0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71–0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower –0.57 (95% CI 0.54–0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73–0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/.

Conclusions

The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.

Copyright

Corresponding author

Author for correspondence: Luis Augusto Rohde, E-mail: lrohde@terra.com.br

References

Hide All
The MTA Cooperative Group (1999) A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Archives of General Psychiatry 56, 10731086.
Agnew-Blais, JC, Polanczyk, GV, Danese, A, Wertz, J, Moffitt, TE and Arseneault, L (2016) Evaluation of the persistence, remission, and emergence of attention-deficit/hyperactivity disorder in young adulthood. JAMA Psychiatry 73, 713720.
Anstey, KJ, Cherbuin, N, Herath, PM, Qiu, C, Kuller, LH, Lopez, OL, Wilson, RS and Fratiglioni, L (2014) A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: the ANU-ADRI. PLoS ONE 9, e86141.
Asherson, P, Buitelaar, J, Faraone, SV and Rohde, LA (2016) Adult attention-deficit hyperactivity disorder: key conceptual issues. The Lancet. Psychiatry 3, 568578.
Bitton, A and Gaziano, TA (2010) The Framingham Heart Study's impact on global risk assessment. Progress in Cardiovascular Diseases 53, 6878.
Boyd, A, Golding, J, Macleod, J, Lawlor, DA, Fraser, A, Henderson, J, Molloy, L, Ness, A, Ring, S and Davey Smith, G (2013) Cohort profile: the ‘children of the 90s’ – the index offspring of the Avon Longitudinal Study of Parents and Children. International Journal of Epidemiology 42, 111127.
Brent, DA, Brunwasser, SM, Hollon, SD, Weersing, VR, Clarke, GN, Dickerson, JF, Beardslee, WR, Gladstone, TR, Porta, G, Lynch, FL, Iyengar, S and Garber, J (2015) Effect of a cognitive-behavioral prevention program on depression 6 years after implementation among at-risk adolescents: a randomized clinical trial. JAMA Psychiatry 72, 11101118.
Buntrock, C, Ebert, DD, Lehr, D, Smit, F, Riper, H, Berking, M and Cuijpers, P (2016) Effect of a web-based guided self-help intervention for prevention of major depression in adults with subthreshold depression: a randomized clinical trial. JAMA 315, 18541863.
Caye, A, Rocha, TB, Anselmi, L, Murray, J, Menezes, AM, Barros, FC, Goncalves, H, Wehrmeister, F, Jensen, CM, Steinhausen, HC, Swanson, JM, Kieling, C and Rohde, LA (2016 a) Attention-deficit/hyperactivity disorder trajectories from childhood to young adulthood: evidence from a birth cohort supporting a late-onset syndrome. JAMA Psychiatry 73, 705712.
Caye, A, Spadini, AV, Karam, RG, Grevet, EH, Rovaris, DL, Bau, CH, Rohde, LA and Kieling, C (2016 b) Predictors of persistence of ADHD into adulthood: a systematic review of the literature and meta-analysis. European Child & Adolescent Psychiatry 25, 11511159.
Caye, A, Swanson, J, Thapar, A, Sibley, M, Arseneault, L, Hechtman, L, Arnold, LE, Niclasen, J, Moffitt, T and Rohde, LA (2016 c) Life span studies of ADHD-conceptual challenges and predictors of persistence and outcome. Current Psychiatry Reports 18, 111.
Caye, A, Sibley, MH, Swanson, JM and Rohde, LA (2017) Late-onset ADHD: understanding the evidence and building theoretical frameworks. Current Psychiatry Reports 19, 106.
Chang, Z, Lichtenstein, P, D'Onofrio, BM, Sjolander, A and Larsson, H (2014) Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: a population-based study. JAMA Psychiatry 71, 319325.
Chia, YC, Gray, SY, Ching, SM, Lim, HM and Chinna, K (2015) Validation of the Framingham general cardiovascular risk score in a multiethnic Asian population: a retrospective cohort study. BMJ Open 5, e007324.
Collins, GS, Reitsma, JB, Altman, DG and Moons, KG (2015) Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD). Annals of Internal Medicine 162, 735736.
Cooper, M, Hammerton, G, Collishaw, S, Langley, K, Thapar, A, Dalsgaard, S, Stergiakouli, E, Tilling, K, Davey Smith, G, Maughan, B, O'Donovan, M, Thapar, A and Riglin, L (2018) Investigating late-onset ADHD: a population cohort investigation. Journal of Child Psychology and Psychiatry 59, 11051113.
Cortese, S, Faraone, SV, Bernardi, S, Wang, S and Blanco, C (2013) Adult attention-deficit hyperactivity disorder and obesity: epidemiological study. British Journal of Psychiatry 203, 2434.
Cross-Disorder Group of the Psychiatric Genomics C, Lee, SH, Ripke, S, Neale, BM, Faraone, SV, Purcell, SM, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayes, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DH, Bloss, CS, Boehnke, M, Boomsma, DI, Breen, G, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Cloninger, CR, Collier, DA, Cook, EH, Coon, H, Cormand, B, Corvin, A, Coryell, WH, Craig, DW, Craig, IW, Crosbie, J, Cuccaro, ML, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, EJ, Degenhardt, F, Djurovic, S, Donohoe, GJ, Doyle, AE, Duan, J, Dudbridge, F, Duketis, E, Ebstein, RP, Edenberg, HJ, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, AE, Ferrier, IN, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, NB, Freitag, CM, Friedl, M, Frisen, L, Gallagher, L, Gejman, PV, Georgieva, L, Gershon, ES, Geschwind, DH, Giegling, I, Gill, M, Gordon, SD, Gordon-Smith, K, Green, EK, Greenwood, TA, Grice, DE, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, JL, Hakonarson, H, Hallmayer, J, Hamilton, SP, Hamshere, ML, Hansen, TF, Hartmann, AM, Hautzinger, M, Heath, AC, Henders, AK, Herms, S, Hickie, IB, Hipolito, M, Hoefels, S, Holmans, PA, Holsboer, F, Hoogendijk, WJ, Hottenga, JJ, Hultman, CM, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, EG, Jones, I, Jones, L, Tzeng, JY, Kahler, AK, Kahn, RS, Kandaswamy, R, Keller, MC, Kennedy, JL, Kenny, E, Kent, L, Kim, Y, Kirov, GK, Klauck, SM, Klei, L, Knowles, JA, Kohli, MA, Koller, DL, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landen, M, Langstrom, N, Lathrop, M, Lawrence, J, Lawson, WB, Leboyer, M, Ledbetter, DH, Lee, PH, Lencz, T, Lesch, KP, Levinson, DF, Lewis, CM., Li, J, Lichtenstein, P, Lieberman, JA, Lin, DY, Linszen, DH, Liu, C, Lohoff, FW, Loo, SK, Lord, C, Lowe, JK, Lucae, S, MacIntyre, DJ, Madden, PA, Maestrini, E, Magnusson, PK, Mahon, PB, Maier, W, Malhotra, AK, Mane, SM, Martin, CL, Martin, NG, Mattheisen, M, Matthews, K, Mattingsdal, M, McCarroll, SA, McGhee, KA, McGough, JJ, McGrath, PJ, McGuffin, P, McInnis, MG, McIntosh, A, McKinney, R, McLean, AW, McMahon, FJ, McMahon, WM, McQuillin, A, Medeiros, H, Medland, SE, Meier, S, Melle, I, Meng, F, Meyer, J, Middeldorp, CM, Middleton, L, Milanova, V, Miranda, A, Monaco, AP, Montgomery, GW, Moran, JL, Moreno-De-Luca, D, Morken, G, Morris, DW, Morrow, EM, Moskvina, V, Muglia, P, Muhleisen, TW, Muir, WJ, Muller-Myhsok, B, Murtha, M, Myers, RM, Myin-Germeys, I, Neale, MC, Nelson, SF, Nievergelt, CM, Nikolov, I, Nimgaonkar, V, Nolen, WA, Nothen, MM, Nurnberger, JI, Nwulia, EA, Nyholt, DR, O'Dushlaine, C, Oades, RD, Olincy, A, Oliveira, G, Olsen, L, Ophoff, RA, Osby, U, Owen, MJ, Palotie, A, Parr, JR, Paterson, AD, Pato, CN, Pato, MT, Penninx, BW, Pergadia, ML, Pericak-Vance, MA, Pickard, BS, Pimm, J, Piven, J, Posthuma, D, Potash, JB, Poustka, F, Propping, P, Puri, V., Quested, DJ, Quinn, EM, Ramos-Quiroga, JA, Rasmussen, HB, Raychaudhuri, S, Rehnstrom, K, Reif, A, Ribases, M, Rice, JP, Rietschel, M, Roeder, K, Roeyers, H, Rossin, L, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, AR, Sanders, SJ, Santangelo, SL, Sergeant, JA, Schachar, R, Schalling, M, Schatzberg, AF, Scheftner, WA, Schellenberg, GD, Scherer, SW, Schork, NJ, Schulze, TG, Schumacher, J, Schwarz, M, Scolnick, E, Scott, LJ, Shi, J, Shilling, PD, Shyn, SI, Silverman, JM, Slager, SL, Smalley, SL, Smit, JH, Smith, EN, Sonuga-Barke, EJ, St Clair, D, State, M, Steffens, M, Steinhausen, HC, Strauss, JS, Strohmaier, J, Stroup, TS, Sutcliffe, JS, Szatmari, P., Szelinger, S, Thirumalai, S, Thompson, RC, Todorov, AA, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, EJ, Van Grootheest, G, Van Os, J, Vicente, AM, Vieland, VJ, Vincent, JB, Visscher, PM, Walsh, CA, Wassink, TH, Watson, SJ, Weissman, MM, Werge, T, Wienker, TF, Wijsman, EM, Willemsen, G, Williams, N, Willsey, AJ., Witt, SH, Xu, W, Young, AH, Yu, TW, Zammit, S, Zandi, PP, Zhang, P, Zitman, FG, Zollner, S, Devlin, B, Kelsoe, JR, Sklar, P, Daly, MJ, O'Donovan, MC, Craddock, N, Sullivan, PF, Smoller, JW, Kendler, KS, Wray, NR and International Inflammatory Bowel Disease Genetics C (2013) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45, 984994.
Dalsgaard, S, Ostergaard, SD, Leckman, JF, Mortensen, PB and Pedersen, MG (2015) Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. The Lancet 385, 21902196.
Faraone, SV, Asherson, P, Banaschewski, T, Biederman, J, Buitelaar, JK, Ramos-Quiroga, JA, Rohde, LA, Sonuga-Barke, EJ, Tannock, R and Franke, B (2015) Attention-deficit/hyperactivity disorder. Nature Reviews Disease Primers 1, 15020.
Fusar-Poli, P, Rutigliano, G, Stahl, D, Davies, C, Bonoldi, I, Reilly, T and McGuire, P (2017) Development and validation of a clinically based risk calculator for the transdiagnostic prediction of psychosis. JAMA Psychiatry 74, 493500.
Goncalves, H, Assuncao, MC, Wehrmeister, FC, Oliveira, IO, Barros, FC, Victora, CG, Hallal, PC and Menezes, AM (2014) Cohort profile update: the 1993 Pelotas (Brazil) birth cohort follow-up visits in adolescence. International Journal of Epidemiology 43, 10821088.
Hafeman, DM, Merranko, J, Goldstein, TR, Axelson, D, Goldstein, BI, Monk, K, Hickey, MB, Sakolsky, D, Diler, R, Iyengar, S, Brent, DA, Kupfer, DJ, Kattan, MW and Birmaher, B (2017) Assessment of a person-level risk calculator to predict new-onset bipolar spectrum disorder in youth at familial risk. JAMA Psychiatry 74, 841847.
Harrell, FE Jr., Lee, KL and Mark, DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Statistical Medicine 15, 361387.
Kivipelto, M, Ngandu, T, Laatikainen, T, Winblad, B, Soininen, H and Tuomilehto, J (2006) Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurology 5, 735741.
Manfro, AG, Santoro, M, Polanczyk, GV, Gadelha, A, Pan, PM, Bressan, RA, Brietzke, E, Talarico, F, Belangero, S, Rohde, LA and Salum, GA (2018) Heterotypic trajectories of dimensional psychopathology across the lifespan: the case of youth-onset attention deficit/hyperactivity disorder. Journal of Child Psychology and Psychiatry 60, 533544.
Moffitt, TE and Team, ERS (2002) Teen-aged mothers in contemporary Britain. Journal of Child Psychology and Psychiatry 43, 727742.
Moffitt, TE, Houts, R, Asherson, P, Belsky, DW, Corcoran, DL, Hammerle, M, Harrington, H, Hogan, S, Meier, MH, Polanczyk, GV, Poulton, R, Ramrakha, S, Sugden, K, Williams, B, Rohde, LA and Caspi, A (2015) Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a four-decade longitudinal cohort study. American Journal of Psychiatry 172, 967977.
Morrow, DA, Antman, EM, Charlesworth, A, Cairns, R, Murphy, SA, de Lemos, JA, Giugliano, RP, McCabe, CH and Braunwald, E (2000) TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: an intravenous nPA for treatment of infarcting myocardium early II trial substudy. Circulation 102, 20312037.
Rubin, DB (1987). Multiple Imputation for Nonresponse in Surveys. New York: Wiley.
Shaw, P, Lerch, J, Greenstein, D, Sharp, W, Clasen, L, Evans, A, Giedd, J, Castellanos, FX and Rapoport, J (2006) Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Archives of General Psychiatry 63, 540549.
Sibley, MH, Rohde, LA, Swanson, JM, Hechtman, LT, Molina, BSG, Mitchell, JT, Arnold, LE, Caye, A, Kennedy, TM, Roy, A and Stehli, A and Multimodal Treatment Study of Children with ACG (2017 a). Late-onset ADHD reconsidered with comprehensive repeated assessments between ages 10 and 25. American Journal of Psychiatry 175, 140149.
Sibley, MH, Swanson, JM, Arnold, LE, Hechtman, LT, Owens, EB, Stehli, A, Abikoff, H, Hinshaw, SP, Molina, BSG, Mitchell, JT, Jensen, PS, Howard, AL, Lakes, KD, Pelham, WE and Group MTAC (2017 b) Defining ADHD symptom persistence in adulthood: optimizing sensitivity and specificity. Journal of Child Psychology and Psychiatry 58, 655662.
Sibley, MH, Pelham, WE, Molina, BS, Gnagy, EM, Waxmonsky, JG, Waschbusch, DA, Derefinko, KJ, Wymbs, BT, Garefino, AC, Babinski, DE and Kuriyan, AB (2012) When diagnosing ADHD in young adults emphasize informant reports, DSM items, and impairment. Journal of Consultant and Clinical Psychology 80, 10521061.
Taylor, JA, Valentine, AZ, Sellman, E, Bransby-Adams, K, Daley, D and Sayal, K (2015) A qualitative process evaluation of a randomised controlled trial of a parenting intervention in community (school) settings for children at risk of attention deficit hyperactivity disorder (ADHD). BMC Psychiatry 15, 290.
Weissman, MM, Brown, AS and Talati, A (2011) Translational epidemiology in psychiatry: linking population to clinical and basic sciences. Archives of General Psychiatry 68, 600608.

Keywords

Type Description Title
WORD
Supplementary materials

Caye et al. supplementary material
Caye et al. supplementary material 1

 Word (2.2 MB)
2.2 MB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

A correction has been issued for this article: