April 7, 2021

Adult Onset ADHD: Does it Exist? Is it Distinct from Youth Onset ADHD?

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.
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Swedish Population Study Confirms Association Between ADHD and Height

Nationwide population study in Sweden confirms association between ADHD and shorter height in children and adolescents, suggests stimulant medications are not a factor

A commonly reported risk associated with ADHD medication is reduced growth in height. But studies to date have generally not adequately described or measured possible confounders, such as genetic factors, prenatal factors, or socioeconomic factors. What if ADHD were associated with reduced height even in the absence of medications? 

An international study team explored this question by performing a nationwide population study comparing data from before (1968-1991) and after (1992-2020) the adoption of stimulant therapy for ADHD in Sweden. 

The country’s single-payer health insurance system that connects patient records with all other national registers through unique personal identification numbers makes such analysis possible. Sweden also has military service conscription, which records the heights of 18-year-old males.

The participants were all 14,268 Swedish males with a diagnosis of ADHD who were drafted into military service at any time from 1968 through 2020. 

Up to five non-ADHD controls were identified for each ADHD case, matched by sex (they had to be male), birth year, and county. The total number of controls was 71,339.

Among 34,586 participants in the period before adoption of stimulant medications (1968-1991), those diagnosed with ADHD had roughly 30% greater odds of being shorter than normal (166-172 vs. 173-185 cm) than typically developing controls. That dropped to 20% greater odds among the 34,714 participants in the cohort following adoption of stimulant medications.

The odds of those diagnosed with ADHD being much shorter than normal (150-165 vs. 173-185 cm) remained identical (about 55% greater) among the almost 30,000 participants in both cohorts.

In other words, there was no increase in the odds of ADHD individuals being shorter than normal after adoption of stimulant therapy in Sweden compared with before such adoption.

Furthermore, after adjusting for known confounders, including birth weight, inflammatory bowel disease, celiac disease, hypothyroidism, anxiety disorders, depression, substance use disorder, and highest parental education, the odds of those diagnosed with ADHD being shorter than normal or much shorter than normal in the 1992-2020 cohort dropped to roughly 10% and 30% greater, respectively.

Could it be the disorder itself rather than stimulant treatment that is associated with reduced height in individuals diagnosed with ADHD?

To address effects of environmental and familial/genetic confounding, the team then compared the entire cohort of males diagnosed with ADHD from 1968 through 2020 with typically developing male relatives, ranging from first cousins to full siblings.

Among full siblings, the odds of those with ADHD diagnoses being shorter (over 90,000 participants) or much shorter (over 77,000 participants) were a statistically significant 14% and 18%, respectively.

The authors concluded, “Our findings suggest that ADHD is associated with shorter height. On a population level, this association was present both before and after ADHD-medications were available in Sweden. The association between ADHD and height was partly explained by prenatal factors, psychiatric comorbidity, low SES [socioeconomic status] and a shared familial liability for ADHD.”

January 9, 2024

Swedish nationwide population study finds mothers with ADHD have elevated risk of depression and anxiety disorders after childbirth

Swedish nationwide population study finds mothers with ADHD have elevated risk of depression and anxiety disorders after childbirth

In the general population, most mothers experience mood disturbances right after childbirth, commonly known as postpartum blues, baby blues, or maternity blues. Yet only about one in six develop symptoms with a duration and magnitude that require treatment for depressive disorder, and one in ten for anxiety disorder.

To what extent does ADHD contribute to the risk of such disorders following childbirth? A Swedish study team used the country’s single-payer health insurance database and other national registers to conduct the first nationwide population study to explore this question.

They used the medical birth register to identify all 420,513 women above 15 years of age who gave birth to their first child, and all 352,534 who gave birth to their second child, between 2005 and 2013. They excluded miscarriages. They then looked for diagnoses of depression and/or anxiety disorders up to a year following childbirth.

In the study population, 3,515 mothers had been diagnosed with ADHD, and the other 769,532 had no such diagnosis. 

Following childbirth, depression disorders were five times more prevalent among mothers with ADHD than among their non-ADHD peers. Excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

Similarly, anxiety disorders were over five times more prevalent among mothers with ADHD than among their non-ADHD peers. Once again, excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.

The team cautioned, “There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.”

Nevertheless, they concluded, “ADHD is an important risk factor for both depression and anxiety disorders in the postpartum period and should be considered in the post- pregnancy maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders. Parental education prior to conception, psychological surveillance during, and social support after childbirth should be provided to women diagnosed with ADHD.”

December 22, 2023

Meta-analysis suggests acupuncture might offer effective treatment for ADHD, but suffers from methodological flaws

Meta-analysis suggests acupuncture might offer effective treatment for ADHD, but suffers from methodological flaws

Noting that previous “systematic reviews concluded that currently available data on the clinical effectiveness of acupuncture for treating ADHD are yet to be sufficient to support its routine use,” a South Korean study team conducted an updated systematic search of the medical literature for randomized controlled trials (RCTs) comparing acupuncture with drug treatment for children and adolescents with ADHD. There were no restrictions on language or publication type.

Only two of the meta-analyses involved more than two RCTs. 

One of them, of six RCTs with a combined 541 participants, reported total treatment efficacy of acupuncture to be at least equal to that of conventional treatment with ADHD medicines. 

Another, of five RCTs with a total of 351 participants, reported total treatment efficacy of combined acupuncture and ADHD drugs to be at least equal to that of conventional treatment with ADHD medicines.

Two RCTs with a Noting that previous “systematic reviews concluded that currently available data on the clinical effectiveness of acupuncture for treating ADHD are yet to be sufficient to support its routine use,” a South Korean study team conducted an updated systematic search of the medical literature for randomized controlled trials (RCTs) comparing acupuncture with drug treatment for children and adolescents with ADHD. There were no restrictions on language or publication type.

Only two of the meta-analyses involved more than two RCTs. 

One of them, of six RCTs with a combined 541 participants, reported total treatment efficacy of acupuncture to be at least equal to that of conventional treatment with ADHD medicines. 

Another, of five RCTs with a total of 351 participants, reported total treatment efficacy of combined acupuncture and ADHD drugs to be at least equal to that of conventional treatment with ADHD medicines.

Two RCTs with a combined 152 participants reported a large effect size improvement in hyperactivity/impulsivity symptoms from acupuncture treatment versus conventional drug treatment.

From this one could superficially conclude that acupuncture is at least as effective for treating ADHD as the medicines currently considered to be the standard of care, and that there is no need to combine acupuncture with drug treatment.

However, there were numerous methodological shortcomings:

  • No effort was made to look for publication bias.
  • There were few RCTs, and the combined number of participants was relatively small.
  • Only one of the six RCTs in the first meta-analysis and none of the five RCTs in the second meta-analysis was rated “low risk of bias.”
  • Though nowhere stated in the journal article, there may have been cultural bias as well. All studies included in the meta-analyses were conducted in China. As China has emerged as a global superpower, it has been eager to portray its traditional medicine as at least equal if not superior to forms of medicine originating elsewhere.
  • The authors noted, “the quality of the studies included in this systematic review was poor. Assessing the blinding of studies is a major aspect in determining the risk of bias of a study, but most of the studies did not provide any relevant information.” 

The authors concluded, “The current evidence on AT [acupuncture treatment] is still too limited to support its routine use in treating ADHD.”

152 participants reported a large effect size improvement in hyperactivity/impulsivity symptoms from acupuncture treatment versus conventional drug treatment.

From this one could superficially conclude that acupuncture is at least as effective for treating ADHD as the medicines currently considered to be the standard of care, and furthermore that there is no need to combine acupuncture with drug treatment.

However, there were numerous methodological shortcomings:

  • No effort was made to look for publication bias.
  • There were few RCTs, and the combined number of participants was relatively small.
  • Only one of the six RCTs in the first meta-analysis and none of the five RCTs in the second meta-analysis was rated “low risk of bias.”
  • Though nowhere stated in the journal article, there may have been cultural bias as well. All studies included in the meta-analyses were conducted in China. As China has emerged as a global superpower, it has been eager to portray its traditional medicine as at least equal if not superior to forms of medicine originating elsewhere.
  • The authors noted, “the quality of the studies included in this systematic review was poor. Assessing the blinding of studies is a major aspect in determining the risk of bias of a study, but most of the studies did not provide any relevant information.” 

The authors concluded, “The current evidence on AT [acupuncture treatment] is still too limited to support its routine use in treating ADHD.”

January 4, 2024