April 7, 2021
There is a growing interest (and controversy) in 'adult-onset ADHD. No current diagnostic system allows for the diagnosis of ADHD in adulthood, yet clinicians sometimes face adults who meet all criteria for ADHD, except for age at onset. Although many of these clinically referred adult-onset cases may reflect poor recall, several recent longitudinal population studies have claimed to detect cases of adult-onset ADHD that showed no signs of ADHD as a youth (Agnew-Blais, Polanczyk et al. 2016, Caye, Rocha, et al. 2016). They conclude, not only that ADHD can onset in adulthood, but that childhood-onset and adult-onset ADHD may be distinct syndromes(Moffitt, Houts, et al. 2015)
In each study, the prevalence of adult-onset ADHD was much larger than the prevalence of childhood-onset adult ADHD). These estimates should be viewed with caution. The adults in two of the studies were 18-19 years old. That is too small a slice of adulthood to draw firm conclusions. As discussed elsewhere (Faraone and Biederman 2016), the claims for adult-onset ADHD are all based on population as opposed to clinical studies.
Population studies are plagued by the "false positive paradox", which states that, even when false positive rates are low, many or even most diagnoses in a population study can be false.
Another problem is that the false positive rate is sensitive to the method of diagnosis. The child diagnoses in the studies claiming the existence of adult-onset ADHDused reports from parents and/or teachers but the adult diagnoses were based on self-report. Self-reports of ADHD in adults are less reliable than informant reports, which raises concerns about measurement error. Another longitudinal study found that current symptoms of ADHD were under-reported by adults who had had ADHD in childhood and over-reported by adults who did not have ADHD in childhood(Sibley, Pelham, et al. 2012). These issues strongly suggest that the studies claiming the existence of adult-onset ADHD underestimated the prevalence of persistent ADHD and overestimated the prevalence of adult-onset ADHD. Thus, we cannot yet accept the conclusion that most adults referred to clinicians with ADHD symptoms will not have a history of ADHD in youth.
The new papers conclude that child and adult ADHD are "distinct syndromes", "that adult ADHD is more complex than a straightforward continuation of the childhood disorder" and that adult ADHD is "not a neurodevelopmental disorder". These conclusions are provocative, suggesting a paradigm shift in how we view adulthood and childhood ADHD. Yet they seem premature. In these studies, people were categorized as adult-onset ADHD if full-threshold add had not been diagnosed in childhood. Yet, in all of these population studies, there was substantial evidence that the adult-onset cases were not neurotypical in adulthood (Faraone and Biederman 2016). Notably, in a study of referred cases, one-third of late adolescent and adult-onset cases had childhood histories of ODD, CD, and school failure(Chandra, Biederman, et al. 2016). Thus, many of the "adult onsets" of ADHD appear to have had neurodevelopmental roots.
Looking through a more parsimonious lens, Faraone and Biederman(2016)proposed that the putative cases of adult-onset ADHD reflect the existence of subthreshold childhood ADHD that emerges with full threshold diagnostic criteria in adulthood. Other work shows that subthreshold ADHD in childhood predicts onsets of full-threshold ADHD in adolescence(Lecendreux, Konofal, et al. 2015). Why is onset delayed in subthreshold cases? One possibility is that intellectual and social supports help subthreshold ADHD youth compensate in early life, with decompensation occurring when supports are removed in adulthood or the challenges of life increase. A related possibility is that the subthreshold cases are at the lower end of a dimensional liability spectrum that indexes risk for onset of ADHD symptoms and impairments. This is consistent with the idea that ADHD is an extreme form of a dimensional trait, which is supported by twin and molecular genetic studies(Larsson, Anckarsater, et al. 2012, Lee, Ripke, et al. 2013). These data suggest that disorders emerge when risk factors accumulate over time to exceed a threshold. Those with lower levels of risk at birth will take longer to accumulate sufficient risk factors and longer to onset.
In conclusion, it is premature to accept the idea that there exists an adult-onset form of ADHD that does not have its roots in neurodevelopment and is not expressed in childhood. It is, however, the right time to carefully study apparent cases of adult-onset ADHD to test the idea that they are late manifestations of a subthreshold childhood condition.
Agnew-Blais, J. C., G.V. Polanczyk, A. Danese, J. Wertz, T. E. Moffitt and L. Arseneault (2016)."Persistence, Remission and Emergence of ADHD in Young Adulthood:Resultsfrom a Longitudinal, Prospective Population-Based Cohort." JAMA.Caye, A., T. B.-M. Rocha, L. Luciana Anselmi, J. Murray, A. M.B. Menezes, F. C. Barros, H. Gonçalves, F. Wehrmeister, C. M. Jensen, H.-C.Steinhausen, J. M. Swanson, C. Kieling and L. A. Rohde (2016). "ADHD doesnot always begin in childhood: E 1 vidence from a large birth cohort." JAMA.
Chandra, S., J. Biederman and S. V. Faraone (2016)."Assessing the Validity of the Ageat Onset Criterion for Diagnosing ADHD in DSM-5." J Atten Disord.
Faraone, S. V. and J. Biederman (2016). "CanAttention-Deficit/Hyperactivity Disorder Onset Occur in Adulthood?" JAMAPsychiatry.
Larsson, H., H. Anckarsater, M. Rastam, Z. Chang and P.Lichtenstein (2012). "Childhood attention-deficit hyperactivity disorderas an extreme of a continuous trait: a quantitative genetic study of 8,500 twinpairs." J Child Psychol Psychiatry53(1): 73-80.
Lecendreux, M., E. Konofal, S. Cortese and S. V. Faraone(2015). "A 4-year follow-up of attention-deficit/hyperactivity disorder ina population sample." J Clin Psychiatry76(6): 712-719.
Lee, S. H., S. Ripke, B. M. Neale, S. V. Faraone, S. M.Purcell, R. H. Perlis, B. J. Mowry, A. Thapar, M. E. Goddard, J. S. Witte, D.Absher, I. Agartz, H. Akil, F. Amin, O. A. Andreassen, A. Anjorin, R. Anney, V.Anttila, D. E. Arking, P. Asherson, M. H. Azevedo, L. Backlund, J. A. Badner,A. J. Bailey, T. Banaschewski, J. D. Barchas, M. R. Barnes, T. B. Barrett, N.Bass, A. Battaglia, M. Bauer, M. Bayes, F. Bellivier, S. E. Bergen, W.Berrettini, C. Betancur, T. Bettecken, J. Biederman, E. B. Binder, D. W. Black,D. H. Blackwood, C. S. Bloss, M. Boehnke, D. I. Boomsma, G. Breen, R. Breuer,R. Bruggeman, P. Cormican, N. G. Buccola, J. K. Buitelaar, W. E. Bunney, J. D.Buxbaum, W. F. Byerley, E. M. Byrne, S. Caesar, W. Cahn, R. M. Cantor, M.Casas, A. Chakravarti, K. Chambert, K. Choudhury, S. Cichon, C. R. Cloninger,D. A. Collier, E. H. Cook, H. Coon, B. Cormand, A. Corvin, W. H. Coryell, D. W.Craig, I. W. Craig, J. Crosbie, M. L. Cuccaro, D. Curtis, D. Czamara, S. Datta,G. Dawson, R. Day, E. J. De Geus, F. Degenhardt, S. Djurovic, G. J. Donohoe, A.E. Doyle, J. Duan, F. Dudbridge, E. Duketis, R. P. Ebstein, H. J. Edenberg, J.Elia, S. Ennis, B. Etain, A. Fanous, A. E. Farmer, I. N. Ferrier, M.Flickinger, E. Fombonne, T. Foroud, J. Frank, B. Franke, C. Fraser, R.Freedman, N. B. Freimer, C. M. Freitag, M. Friedl, L. Frisen, L. Gallagher, P.V. Gejman, L. Georgieva, E. S. Gershon, D. H. Geschwind, I. Giegling, M. Gill,S. D. Gordon, K. Gordon-Smith, E. K. Green, T. A. Greenwood, D. E. Grice, M.Gross, D. Grozeva, W. Guan, H. Gurling, L. De Haan, J. L. Haines, H. Hakonarson,J. Hallmayer, S. P. Hamilton, M. L. Hamshere, T. F. Hansen, A. M. Hartmann, M.Hautzinger, A. C. Heath, A. K. Henders, S. Herms, I. B. Hickie, M. Hipolito, S.Hoefels, P. A. Holmans, F. Holsboer, W. J. Hoogendijk, J. J. Hottenga, C. M.Hultman, V. Hus, A. Ingason, M. Ising, S. Jamain, E. G. Jones, I. Jones, L.Jones, J. Y. Tzeng, A. K. Kahler, R. S. Kahn, R. Kandaswamy, M. C. Keller, J.L. Kennedy, E. Kenny, L. Kent, Y. Kim, G. K. Kirov, S. M. Klauck, L. Klei, J.A. Knowles, M. A. Kohli, D. L. Koller, B. Konte, A. Korszun, L. Krabbendam, R.Krasucki, J. Kuntsi, P. Kwan, M. Landen, N. Langstrom, M. Lathrop, J. Lawrence,W. B. Lawson, M. Leboyer, D. H. Ledbetter, P. H. Lee, T. Lencz, K. P. Lesch, D.F. Levinson, C. M. Lewis, J. Li, P. Lichtenstein, J. A. Lieberman, D. Y. Lin,D. H. Linszen, C. Liu, F. W. Lohoff, S. K. Loo, C. Lord, J. K. Lowe, S. Lucae,D. J. MacIntyre, P. A. Madden, E. Maestrini, P. K. Magnusson, P. B. Mahon, W.Maier, A. K. Malhotra, S. M. Mane, C. L. Martin, N. G. Martin, M. Mattheisen,K. Matthews, M. Mattingsdal, S. A. McCarroll, K. A. McGhee, J. J. McGough, P.J. McGrath, P. McGuffin, M. G. McInnis, A. McIntosh, R. McKinney, A. W. McLean,F. J. McMahon, W. M. McMahon, A. McQuillin, H. Medeiros, S. E. Medland, S.Meier, I. Melle, F. Meng, J. Meyer, C. M. Middeldorp, L. Middleton, V.Milanova, A. Miranda, A. P. Monaco, G. W. Montgomery, J. L. Moran, D.Moreno-De-Luca, G. Morken, D. W. Morris, E. M. Morrow, V. Moskvina, P. Muglia,T. W. Muhleisen, W. J. Muir, B. Muller-Myhsok, M. Murtha, R. M. Myers, I.Myin-Germeys, M. C. Neale, S. F. Nelson, C. M. Nievergelt, I. Nikolov, V.Nimgaonkar, W. A. Nolen, M. M. Nothen, J. I. Nurnberger, E. A. Nwulia, D. R.Nyholt, C. O'Dushlaine, R. D. Oades, A. Olincy, G. Oliveira, L. Olsen, R. A.Ophoff, U. Osby, M. J. Owen, A. Palotie, J. R. Parr, A. D. Paterson, C. N.Pato, M. T. Pato, B. W. Penninx, M. L. Pergadia, M. A. Pericak-Vance, B. S.Pickard, J. Pimm, J. Piven, D. Posthuma, J. B. Potash, F. Poustka, P. Propping,V. Puri, D. J. Quested, E. M. Quinn, J. A. Ramos-Quiroga, H. B. Rasmussen, S.Raychaudhuri, K. Rehnstrom, A. Reif, M. Ribases, J. P. Rice, M. Rietschel, K.Roeder, H. Roeyers, L. Rossin, A. Rothenberger, G. Rouleau, D. Ruderfer, D.Rujescu, A. R. Sanders, S. J. Sanders, S. L. Santangelo, J. A. Sergeant, R.Schachar, M. Schalling, A. F. Schatzberg, W. A. Scheftner, G. D. Schellenberg,S. W. Scherer, N. J. Schork, T. G. Schulze, J. Schumacher, M. Schwarz, E.Scolnick, L. J. Scott, J. Shi, P. D. Shilling, S. I. Shyn, J. M. Silverman, S.L. Slager, S. L. Smalley, J. H. Smit, E. N. Smith, E. J. Sonuga-Barke, D. StClair, M. State, M. Steffens, H. C. Steinhausen, J. S. Strauss, J. Strohmaier,T. S. Stroup, J. S. Sutcliffe, P. Szatmari, S. Szelinger, S. Thirumalai, R. C.Thompson, A. A. Todorov, F. Tozzi, J. Treutlein, M. Uhr, E. J. van den Oord, G.Van Grootheest, J. Van Os, A. M. Vicente, V. J. Vieland, J. B. Vincent, P. M.Visscher, C. A. Walsh, T. H. Wassink, S. J. Watson, M. M. Weissman, T. Werge,T. F. Wienker, E. M. Wijsman, G. Willemsen, N. Williams, A. J. Willsey, S. H.Witt, W. Xu, A. H. Young, T. W. Yu, S. Zammit, P. P. Zandi, P. Zhang, F. G.Zitman, S. Zollner, B. Devlin, J. R. Kelsoe, P. Sklar, M. J. Daly, M. C.O'Donovan, N. Craddock, P. F. Sullivan, J. W. Smoller, K. S. Kendler and N. R.Wray (2013). "Genetic relationship between five psychiatric disordersestimated from genome-wide SNPs." Nat Genet45(9): 984-994.
Moffitt, T. E., R. Houts, P. Asherson, D. W. Belsky, D. L.Corcoran, M. Hammerle, H. Harrington, S. Hogan, M. H. Meier, G. V. Polanczyk,R. Poulton, S. Ramrakha, K. Sugden, B. Williams, L. A. Rohde and A. Caspi(2015). "Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder?Evidence From a Four-Decade Longitudinal Cohort Study." Am J Psychiatry:appiajp201514101266.
Sibley, M. H., W. E. Pelham, B.S. Molina, E. M. Gnagy, J. G. Waxmonsky, D. A. Waschbusch, K. J. Derefinko, B.T. Wymbs, A. C. Garefino, D. E. Babinski and A. B. Kuriyan (2012). "Whendiagnosing ADHD in young adults emphasize informant reports, DSM items, and impairment."J Consult Clin Psychol80(6):1052-1061.
Precocious puberty (PP) is defined as the onset of secondary sex characteristics before age 8 in girls or age 9 in boys.
Because it accelerates skeletal maturation by prematurely shutting down the cartilage growth plate at the tip of long bones, it tends to lead to shorter height in adulthood. It is also known to place an additional psychological burden on children, especially girls. Girls are four to 38 times more likely to develop PP than boys.
Taiwan has a single-payer national health insurance system, called National Health Insurance, that encompasses 99.6% of the island’s population. The Ministry of Health and Welfare uses it to maintain the National Health Insurance Research Database (NHIRD), enabling researchers to conduct nationwide population studies.
Using this database, a Taiwanese study team investigated the relationship between ADHD and precocious puberty among children and adolescents (under 18). And because methylphenidate (MPH) is the only psychostimulant approved for the treatment of ADHD in Taiwan, the team also explored the effect of MPH on this relationship.
Most diagnoses of ADHD in the NHIRD are made by board-certified psychiatrists, enhancing diagnostic validity.
Of the more than 3.3 million persons born in Taiwan between 1997 and 2001, 186,681 were diagnosed with ADHD. Of these, 122,302 were prescribed MPH.
After adjusting for sex, low-income households, and neuropsychiatric comorbidities, children diagnosed with ADHD were twice as likely to be diagnosed with PP. This held equally true for boys and girls.
However, children diagnosed with ADHD and prescribed MPH were more than a third less likely to subsequently be diagnosed with PP than those diagnosed with ADHD but not prescribed MPH.
For girls with ADHD, who without an MPH prescription were nine times more likely than boys with ADHD to be diagnosed with PP, an MPH prescription reduced that ratio to five times more likely than boys with ADHD and prescribed MPH.
That suggests a strong protective effect of MPH.
The team concluded, “Our study found that children with ADHD were at a greater risk of PP, and girls with ADHD were a particularly vulnerable group. … MPH appeared to be protective against PP in patients with ADHD, especially in girls. However, these preliminary results need further validation.”
Maternal infections and inflammatory responses during pregnancy have been proposed as risk factors for neurodevelopmental disorders such as ADHD.
Taiwan has a single-payer health insurance system that covers virtually the entirety of its population. Its Ministry of Health and Welfare maintains the National Health Insurance Research Database (NHIRD), with detailed information on outpatient services, hospitalizations, and medical treatment for nearly 99% of all residents.
A Taiwanese study team used NHIRD to examine to examine the relationship between maternal hospitalization for infection, and early childhood infection, and subsequent ADHD in offspring. The study cohort originated with all 3,260,879 individuals born between 2001 and 2018.
The team excluded births from foreign mothers, still births, births with congenital defects, low birth weights, abnormally late births, twins, triplets, and other multiple births, culminating in a final population cohort of 2,885,662 live-born single infants across 1,893,171 families, and 1,864,660 individuals with full siblings from 872,169 families comprising the full sibling cohort.
Study participants were followed until diagnosis of a neurodevelopmental disorder, their death, or the end of 2021.
After adjusting for sex, birth year, paternal and maternal ages, birthweight, birth season, parity, delivery method, 1 minute APGAR score (evaluating baby’s appearance, pulse, grimace, activity and respiration at birth), gestational age, pregnancy and delivery complications, parental history of neurodevelopmental disorders, maternal asthma and diabetes, urbanization level of the residential area, and family’s insurance amount, offspring of mothers hospitalized for infections had 14% greater odds of being subsequently diagnosed with ADHD.
However, in the full sibling cohort of over 1.8 million, this association vanished. That held true for each of the three trimesters of pregnancy. It also held true for bacterial infections. Surprisingly, offspring of mothers hospitalized for viral infections were 24% less likely to be diagnosed with ADHD than their siblings not exposed to maternal viral infection. Because of that, they also had a 6% lower risk overall.
After the same adjustments, early childhood infection was associated with 16% greater odds of being diagnosed with ADHD.
Nevertheless, in the full sibling cohort of over 1.8 million, this association again vanished. That held true overall, as well as separately for childhood infections in months 1-6 and months 7-12. The association vanished altogether both for bacterial infections as well as for viral infections.
The authors concluded, “the results of this nationwide birth cohort study with population and sibling analyses suggest that the association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors.”
Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time.
An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107 children who have been followed up every two years since birth.
The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.
Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year.
The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ).
Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10.
With diagnosis of ADHD at age 10 and all other factors held constant:
Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect.
Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes.
Conclusion:
The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.”
While factors like depression and bullying contribute, ADHD itself remains a key risk factor. Early intervention and strong mental health support are crucial to protecting these children’s well-being.
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