Neural Correlates of ADHD

Lenard A. Adler, on September 29, 2016

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults
with Attention-Deficit/Hyperactivity Disorder, Zhen Yang, PhD, Clare Kelly, PhD, Francisco X. Castellanos, MD, Terry Leon, MS, Michael P. Milham, MD, PhD, and Lenard A. Adler, MD
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY, p. 1–10,DOI: 10.1089/cap.2015.0243

Several prior studies have examined effects of stimulant medications on functional connectivity during resting state fMRI (R-fMRI). This study appears to be the first study to examine effects of ADHD treatment on functional connectivity in adults. Nineteen adults with ADHD were received two, six minute R-fMRI scans at baseline and after three weeks of single-blind treatment with amphetamine (mixed amphetamine salts (MAS) or lisdexamfetamine (LDX)).

A comparison group of healthy controls (HC) was scanned once at baseline. Potential amphetamine effects on the entire connectome relating to R-fMRI were examined through a data driven analytic approach. Clinical effects of amphetamines on ADHD symptoms were examined via the prompted ADHD Rating Scale (ADHD-RS) administered by a clinician and the Adult Self Report Scale (ASRS) v1.1 Symptom Checklist. MAS and LDX both significantly improved ADHD symptoms on the ADHD-RS and ASRS. Functional connectivity analyses showed that stimulants altered multivariate connectivity in medial prefrontal cortex (MPFC)/paracingulate gyrus and the dorsolateral PFC. Seed based correlation analyses were defined for the left DLPFC and bilateral MPFC. Functional connectivity analyses showed that amphetamines decreased positive functional connectivity between: a) left DLPFC and bilateral dorsal ACC, right insula and left insula and b) bilateral MPFC. These reductions in functional connectivity led to a pattern of function similar to the healthy controls, which is important as the increased functional segregation of these units may be involved in the improvement with amphetamine treatment. Although these results cannot be directly translated into the clinic, they hold open the promise that, in the future, imaging methodologies may be useful for either predicting or tracking treatment response.

ADHD and Cognitive Function in Older Adults

Lenard A. Adler, on September 22, 2016

E. J. Semeijn, N. C. M. Korten, H. C. Comijs, M. Michielsen, D. J. H. Deeg, A. T. F. Beekman and J. J. S. Kooij. No lower cognitive functioning in older adults with attention-deficit/hyperactivity disorder. International Psychogeriatrics: International Psychogeriatric Association 2015 doi:10.1017/S1041610215000010.

The largest percentage growth in stimulant prescriptions in the last year is in adults over the age of 50 years of age (Adler LA. ADHD in Older Adults. Paper Presentation at the Annual Meeting of the American Psychiatric Association, New York , New York, May 2014). Even though stimulant prescriptions may be increasing in older adults with ADHD, the number of studies which have examined older adults with ADHD is relatively small. One concern in studying adults with ADHD is the potential confound of cognitive decline that may occur with aging in assessing ADHD symptoms. This study examined the cognitive function of older adults without ADHD vs. those with ADHD (n=231) in the Longitudinal Study Amsterdam (LASA). Cognitive function was assessed via neuropsychological measures of functioning, information processing speed, memory, and attention/working memory. The authors only found a negative association of ADHD symptom severity and attention/working memory domain; however, when depressive symptoms were controlled for, this association was no longer significant. Neuropsychological impairments in attention and working memory have also been shown in younger adults with ADHD. This study highlights the need for further investigations of cognitive functioning in older adults with ADHD and the importance of screening for depression in these individuals.

Stimulant Medication and Psychotic Symptoms in Offspring of Parents With Mental Illness

Anthony L. Rostain, MD MA on September 8, 2016

Pediatrics 2016; 137(1);e20152486
“Stimulant Medication and Psychotic Symptoms in Offspring of Parents With Mental Illness”
MacKenzie, L.E., Abidi, S., Fisher, H.L. et al.

Treatment of ADHD with stimulant medications carries many known risks including the development of psychotic symptoms which is considered to be a rare adverse event. It is reported that between 0.25% – 1.5% of children taking stimulants develop psychotic symptoms. However, little is known about the nature of these symptoms or about the potential for higher rates of psychosis in at-risk populations such as the children of parents with serious mental illness (SMI). Case reports and a chart review report that the rate of stimulant-induced psychosis in this group ranges from 8% to 20%. The authors of this paper set out study the rates and types of psychotic symptoms in children with parents suffering SMIs such as major depression, bipolar disorder and schizophrenia. They carefully evaluated 141 children (ages 6-21 years, average 11.8 years) in a study of developmental psychopathology in offspring of parents with SMI in Nova Scotia entitled “Families Overcoming Risks and Building Opportunities for Wellbeing.” The study employed several standardized interviews to inquire into a variety of psychiatric conditions including the occurrence and the nature of psychotic symptoms experienced by these children. All youths and parents were interviewed using the Kiddie SADS and three other interviews that probe for prodromal syndromes, psychotic-like experiences and proneness to schizophrenia. The rates of psychotic symptoms were reported for the entire sample and the rates were compared between children receiving stimulant medications (N=24) and those who never took a stimulant. Moderators such as parental diagnosis and presence or absence of ADHD in the child were also analyzed.

Of the 24 children receiving stimulant medication, 15 (62.5%) developed psychotic and related symptoms compared with 32 (27.4%) of the remaining 117 participants who had never taken stimulants. The adjusted odds ratio for psychotic symptoms due to stimulant medication was found to be 4.41. Further analyses revealed a stronger effect of stimulant medication (OR: 4.51) and a very weak effect of ADHD (OR: 1.16) on the development of psychosis. No differences were seen in rates of psychosis when analyzing parental psychopathology. Psychotic symptoms were seen in 37.5% of children of parents with schizophrenia, 34% of parents with bipolar disorder and 32% of parents with major depressive disorder. All of the children with medication-induced psychosis had parents with either bipolar disorder or depressive disorder. By far, the most common psychotic symptoms reported were hallucinations. Lastly, a sensitivity analysis was conducted to determine the temporal relationship between stimulant treatment and the onset of psychotic symptoms. Of the 15 individuals with current stimulant use, 25% developed symptoms; of the 126 participants without current stimulant use, 5% were experiencing psychotic symptoms. The Odds Ratio of developing psychotic symptoms from stimulants was 7.25. Moreover, a subset of children clearly developed psychosis as a result of taking stimulants.

This study was extremely well designed and implemented. It is the first of its kind to carefully document the frequency and nature of psychotic symptoms in children of parents with SMI, and to quantify the considerable added risk to those prescribed stimulant medication. It convincingly demonstrates the substantial risk these children face and suggests that clinicians should be cautious whenever prescribing stimulant medications to this group, and should carefully monitor for the onset of serious adverse effects.

Broken Bones and ADHD

Stephen V. Faraone, PhD on August 25, 2016

Although some people view the impulsivity and inattentiveness of ADHD adults as a normal trait, these symptoms have adverse consequences, which is why doctors consider ADHD to be a disorder. The list of adverse consequences is long and now we can add another: broken bones. A recent study by Komurcu and colleagues examined 40 patients who were seen by doctors because of broken bones and 40 people who had not broken a bone. After measuring ADHD symptoms in these patients, the study found that the patients with broken bones were more impulsive and inattentive than those without broken bones. These data suggest that, compared with others, adults with ADHD symptoms put themselves in situations that lead to broken bones. What could those situations be? Well, we know for starters that ADHD adults are more likely to have traffic accidents. They are also more likely to get into fights due to their impulsivity. As a general observation, it makes sense that people who are inattentive are more likely to have accidents that lead to injuries. When we don’t pay attention, we can put ourselves in dangerous situations. Who should care about these results? ADHD patients need to know about this so that they understand the potential consequences of their disorder. They are exposed to so much media attention to the dangers of drug treatment that it can be easy to forget that non-treatment also has consequences. Cognitive behavior therapy is also useful for helping patients learn how to avoid situations that might lead to accidents and broken bones. This study also has an important message for administrators and how they make decisions about subsidizing or reimbursing treatment for ADHD. They need to know that treating ADHD can prevent outcomes that are costly to the healthcare system, such as broken bones. For example, in a study of children and adolescents, Leibson and colleagues showed that healthcare costs for ADHD patients were twice the cost for other youth, partly due to more hospitalizations and more emergency room visits. Do these data mean that every ADHD patient is doomed to a life of injury and hospital visits? Certainly not. But they do mean that patients and their loved ones need to be cautious and need to seek treatments that can limit the possibility of accidents and injury.
 

REFERENCES
Komurcu, E., Bilgic, A. & Herguner, S. (2014). Relationship between extremity fractures and attention-deficit/hyperactivity disorder symptomatology in adults. Int J Psychiatry Med 47, 55-63.
Leibson, C. L., S. K. Katusic, et al. (2001). “Use and Costs of Medical Care for Children and Adolescents With and Without Attention-Deficit/Hyperactivity Disorder.” Journal of the American Medical Association 285(1): 60-66.

Acetaminophen and ADHD

Stephen V. Faraone, PhD on August 25, 2016

Many media outlets have reported on a study suggesting that mothers who use acetaminophen during pregnancy may put their unborn child at risk for ADHD. Given that acetaminophen is used in many over-the-counter pain killers, correctly reporting such information is crucial. As usual, rather than relying on one study, looking at the big picture using all available studies is best. Because it is not possible to examine this issue with a randomized trial, we must rely on naturalistic studies.

One registry study (http://www.ncbi.nlm.nih.gov/pubmed/24566677) reported that fetal exposure to acetaminophen predicted an increased risk of ADHD with a risk ratio of 1.37. The risk was dose-dependent in the sense that it increased with increased maternal use of acetaminophen. Of particular note, the authors made sure that their results were not accounted for by potential confounds (e.g., maternal fever, inflammation and infection).

Similar results were reported by another group (http://www.ncbi.nlm.nih.gov/pubmed/25251831), which also showed that risk for ADHD was not predicted by maternal use of aspirin, antacids, or antibiotics. But that study only found an increased risk at age 7 (risk ratio = 2.0) not at age 11. In a Spanish study, (http://www.ncbi.nlm.nih.gov/pubmed/27353198), children exposed prenatally to acetaminophen were more likely to show symptoms of hyperactivity and impulsivity later in life. The risk ratio was small (1.1) but it increased with the frequency of prenatal acetaminophen use by their mothers.

We can draw a few conclusions from these studies. There does seem to be a weak, yet real, association between maternal use of acetaminophen while pregnant and subsequent ADHD or ADHD symptoms in the exposed child. The association is weak in several ways: there are not many studies, they are all naturalistic and the risk ratios are small.

So mothers that have used acetaminophen during pregnancy and have an ADHD child should not conclude that their acetaminophen use caused their child’s ADHD. On the other hand, pregnant women who are considering the use of acetaminophen for fever or pain should discuss other options with their physician. As with many medical decisions, one must balance competing risks to make an informed decision.

Side Effects of Acetaminophen – ADHD?

Stephen V. Faraone, PhD on August 25, 2016

Does Acetaminophen use During Pregnancy Cause ADHD in Offspring?

Many media outlets have reported on a study suggesting that mothers who use acetaminophen during pregnancy may put their unborn child at risk for ADHD.   Given that acetaminophen is used in many over-the-counter pain killers, correctly reporting such information is crucial. 

As usual, rather than relying on one study, looking at the big picture using all available studies is best.  Because it is not possible to examine this issue with a randomized trial, we must rely on naturalistic studies.  

One registry study (http://www.ncbi.nlm.nih.gov/pubmed/24566677) reported that fetal exposure to acetaminophen predicted an increased risk of ADHD with a risk ratio of 1.37.  The risk was dose-dependent in the sense that it increased with increased maternal use of acetaminophen.  Of particular note, the authors made sure that their results were not accounted for by potential confounds (e.g., maternal fever, inflammation and infection). 

Similar results were reported by another group, which also showed that risk for ADHD was not predicted by maternal use of aspirin, antacids, or antibiotics.  But that study only found an increased risk at age 7 (risk ratio = 2.0) not at age 11. (http://www.ncbi.nlm.nih.gov/pubmed/25251831)

In a Spanish study, (http://www.ncbi.nlm.nih.gov/pubmed/27353198), children exposed prenatally to acetaminophen were more likely to show symptoms of hyperactivity and impulsivity later in life.  The risk ratio was small (1.1) but it increased with the frequency of prenatal acetaminophen use by their mothers. 

We can draw a few conclusions from these studies.  There does seem to be a weak, yet real, association between maternal use of acetaminophen while pregnant and subsequent ADHD or ADHD symptoms in the exposed child.  The association is weak in several ways: there are not many studies, they are all naturalistic and the risk ratios are small.  

So mothers that have used acetaminophen during pregnancy and have an ADHD child should not conclude that their acetaminophen use caused their child’s ADHD.  On the other hand, pregnant women who are considering the use of acetaminophen for fever or pain should discuss other options with their physician.  As with many medical decisions, one must balance competing risks to make an informed decision.

Supplementary GXR for Adult ADHD

Anthony L. Rostain, MD MA on August 18, 2016

Psychiatry Research 2016 236:136-141. DOI: 10.1016/j.psychres.2015.12.017
“Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study.”
Butterfield ME, Saal J, Young B, Young JI.

Guanfacine hydrochloride is a selective alpha-2A partial agonist that is FDA approved for the treatment of ADHD in children and adolescents (see recent reviews by Faraone et al, 2013; Hirota et al, 2014 and Ruggiero et al 2014). It can be given alone or in combination with psychostimulant medication as its mechanism of action is complementary to these agents. Despite growing scientific evidence of its effectiveness for this age group, very little is known about the potential benefits of guanfacine for the treatment of ADHD in adults. In view of concerns about the importance of finding suitable non-stimulant medications for this population, the authors carried out a randomized placebo controlled trial of extended release guanfacine (GXR) as supplemental treatment for subjects with a suboptimal response to stimulant-only medication treatment.
 
Subjects were recruited from local advertisements and from the clinic practice of the authors in suburban Detroit. Entry criteria included a current diagnosis of ADHD, current treatment with a stimulant medication, and suboptimal response to this medication as evidenced by a score of > 28 on the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) or of > 4 on the Clinical Global Impression – Severity (CGI-S) Scale. Exclusion criteria included having another severe Axis I psychiatric disorder, along with subjects with a history of autism, chemical dependence or psychosis. Subjects with hypertension or any medical condition that might be exacerbated by the study medication. A total of 26 subjects in the age range of 19 – 62 years were recruited for the study, of which roughly 50% were women, and 85% were Caucasian. Subjects were randomly assigned to receive either placebo or incremental doses of GXR ranging from 1 to 6 mg daily on a weekly basis over a 10-week study period.
 
The primary outcome measures were the ADHD Rating Scale and the Clinical Global Impression – Severity. Secondary outcome measures included the Arizona Sexual Experience Questionnaire, the Fatigue Symptom Inventory, the Pittsburgh Sleep Quality Index, the Hamilton Anxiety Inventory and the Hamilton Depression Rating Scale. Baseline and weekly measures of cardiovascular status were collected throughout the study.
 
Contrary to the study authors’ expectations, although subjects in both the placebo and the treatment arms of the study showed significant improvements in both primary and secondary outcome measures, the two groups did not differ from one another. For instance, the mean ADHD-RS score of the placebo group decreased by 10.92 (from 35.23 to 24.31) and that of the GXR treated group decreased by 11.85 (from 35.92 to 24.08). The CGI-S score in the placebo group decreased by 1.00 and that of the GXR group by 0.85. There were no differences between the two groups on measures of tolerability, hemodynamics, sleep, anxiety or depression. Moreover, no treatment x time x group effects were noted.

The authors comment that several explanations can account for these findings including a strong placebo effect, a generalized study effect (i.e. participating in a clinical trial itself may be beneficial in and of itself), a “regression to the mean” effect for the placebo group, and a potential bias induced by participating in a clinical trial. Of note, there were no between group differences seen in fatigue, sleep problems, sexual functioning or in hemodynamic measures – a finding that supports the tolerability and safety of GXR in adult patients.

While this is a “negative study,” it is helpful in clarifying that GXR can be used safely in combination with stimulant medications, that it does not worsen other psychiatric symptoms (e.g. anxiety, depression) and that it may be a helpful adjunctive treatment for adults with ADHD whose stimulant medication is not sufficiently helpful in reducing their symptoms. Further research with a larger sample size and with measures taken to minimize the placebo effect are certainly warranted. In the meantime, clinicians who are considering using GXR can be reassured that it is well tolerated in this population.

 
Faraone SV, McBurnett K, Sallee FR, Steeber J, López FA (2013). Guanfacine extended release: a novel treatment for attention-deficit/hyperactivity disorder in children and adolescents. Clinical Therapeutics Nov;35(11):1778-93. doi: 10.1016/j.clinthera.2013.09.005
Hirota T, Schwartz S, Correll CU (2014). Alpha-2 Agonists for Attention-Deficit/Hyperactivity Disorder in youth: A Systematic Review and Meta-Analysis of Monotherapy and Add-On Trials to Stimulant Therapy. J. Amer.. Acad. Child Adolesc. Psychiatry 53(2):153–173.
Ruggiero S, Clavenna A, Reale L, Capuano A, Rossi F, Bonati M (2014). Guanfacine for attention deficit and hyperactivity disorder in pediatrics: A systematic review and meta-analysis. European Neuropsychopharmacology 24: 1578-1590.

Non-Stimulant ADHD Medication (Guanfacine) as an Adjunct to ADHD Stimulant Medications

Anthony L. Rostain, MD MA on August 18, 2016

A Research Review

Psychiatry Research 2016 236:136-141.  DOI: 10.1016/j.psychres.2015.12.017  “Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study.” Butterfield ME, Saal J, Young B, Young JI.

Guanfacine hydrochloride is a selective alpha-2A partial agonist that is FDA approved for the treatment of ADHD in children and adolescents (see recent reviews by Faraone et al, 2013; Hirota et al, 2014 and Ruggiero et al 2014).  It can be given alone or in combination with psychostimulant medication as its mechanism of action is complementary to these agents.   Despite growing scientific evidence of its effectiveness for this age group, very little is known about the potential benefits of guanfacine for the treatment of ADHD in adults.

In view of concerns about the importance of finding suitable non-stimulant ADHD medications for this population, the authors carried out a randomized placebo controlled trial of extended release guanfacine (GXR) as supplemental treatment for subjects with a suboptimal response to stimulant-only medication treatment. 

Subjects were recruited from local advertisements and from the clinic practice of the authors in suburban Detroit.  Entry criteria included a current diagnosis of ADHD, current treatment with a stimulant medication, and suboptimal response to this medication as evidenced by a score of > 28 on the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) or of > 4 on the Clinical Global Impression – Severity (CGI-S) Scale.  Exclusion criteria included having another severe Axis I psychiatric disorder, along with subjects with a history of autism, chemical dependence or psychosis.  Subjects with hypertension or any medical condition that might be exacerbated by the study medication.  A total of 26 subjects in the age range of 19 – 62 years were recruited for the study, of which roughly 50% were women, and 85% were Caucasian.  Subjects were randomly assigned to receive either placebo or incremental doses of GXR ranging from 1 to 6 mg daily on a weekly basis over a 10-week study period. 


The primary outcome measures were the ADHD Rating Scale and the Clinical Global Impression – Severity.  Secondary outcome measures included the Arizona Sexual Experience Questionnaire, the Fatigue Symptom Inventory, the Pittsburgh Sleep Quality Index, the Hamilton Anxiety Inventory and the Hamilton Depression Rating Scale.  Baseline and weekly measures of cardiovascular status were collected throughout the study. 

Contrary to the study authors’ expectations, although subjects in both the placebo and the treatment arms of the study showed significant improvements in both primary and secondary outcome measures, the two groups did not differ from one another.  For instance, the mean ADHD-RS score of the placebo group decreased by 10.92 (from 35.23 to 24.31) and that of the GXR treated group decreased by 11.85 (from 35.92 to 24.08).  The CGI-S score in the placebo group decreased by 1.00 and that of the GXR group by 0.85.  There were no differences between the two groups on measures of tolerability, hemodynamics, sleep, anxiety or depression.  Moreover, no treatment x time x group effects were noted. 

The authors comment that several explanations can account for these findings including a strong placebo effect, a generalized study effect (i.e. participating in a clinical trial itself may be beneficial in and of itself), a “regression to the mean” effect for the placebo group, and a potential bias induced by participating in a clinical trial.   Of note, there were no between group differences seen in fatigue, sleep problems, sexual functioning or in hemodynamic measures – a finding that supports the tolerability and safety of GXR in adult patients. 

While this is a “negative study,” it is helpful in clarifying that GXR can be used safely in combination with stimulant medications, that it does not worsen other psychiatric symptoms (e.g. anxiety, depression) and that it may be a helpful adjunctive treatment for adults with ADHD whose stimulant medication is not sufficiently helpful in reducing their symptoms.  Further research with a larger sample size and with measures taken to minimize the placebo effect are certainly warranted.  In the meantime, clinicians who are considering using GXR can be reassured that it is well tolerated in this population.

 

Faraone SV, McBurnett K, Sallee FR, Steeber J, López FA (2013). Guanfacine extended release: a novel treatment for attention-deficit/hyperactivity disorder in children and adolescents. Clinical Therapeutics Nov;35(11):1778-93. doi: 10.1016/j.clinthera.2013.09.005

Hirota T, Schwartz S, Correll CU (2014). Alpha-2 Agonists for Attention-Deficit/Hyperactivity Disorder in youth: A Systematic Review and Meta-Analysis of Monotherapy and Add-On Trials to Stimulant Therapy. J. Amer.. Acad. Child Adolesc. Psychiatry 53(2):153–173.

Ruggiero S, Clavenna A, Reale L, Capuano A, Rossi F, Bonati M (2014). Guanfacine for attention deficit and hyperactivity disorder in pediatrics: A systematic review and meta-analysis.  European Neuropsychopharmacology 24: 1578-1590.

ADHD in Older Adults – The Next Clinical Frontier

David W. Goodman, MD, LFAPA on August 11, 2016

Attention Deficit Hyperactivity Disorder is the most common childhood psychiatric disorder and the second most prevalent adult psychiatric disorder second to Major Depression. Yet, until recently, ADHD in adults over age 50 was not identified. As we have come to understand, ADHD symptoms with impairments persist into adulthood for 60% of ADHD children.

For those adults with ADHD, how many will have symptoms that persist for the rest of their lives? How do these symptoms and impairments present? How do we discern ADHD symptoms from other factors contributing to cognitive change with age? How do we obtain clinical history in those patients who can’t remember childhood or adolescent symptoms? Would objective tests differentiate diagnoses? What treatments work well for this age group? What medical considerations are necessary for prescribing ADHD treatments to those with medical illness and multiple medications? What safety parameters need to be considered in this age group when prescribing ADHD medications? What are the drug-drug interactions that may be clinically relevant?

 

For clinicians and researchers, these questions represent opportunities to expand our fund of knowledge to better serve the needs of ADHD patients in all age categories.

 

The population of persons older than 65 years of age in the U.S. will grow from 43.1 million to 88.5 million between 2012 and 2050. A recent review of the literature on ADHD in older adults reports a prevalence rate of 2.8% in the Netherlands, 3.5% in Sweden, and 3.5% in Germany. A meta-analysis of ADHD prevalence in studies utilizing different age ranges spanning 18-78 years suggests that prevalence may decline with age. However, given that these studies used DSM-IV criteria with a symptom age threshold of 7 and the absence of a validated ADHD symptom profile for older adults, these cited prevalences may underestimate the ADHD population.

 

Reliance on childhood ADHD diagnosis to substantiate ADHD in older adults is often not useful because in the National Comorbidity Survey Replication in the U.S., 75% of ADHD adults ages 18-44 had not been diagnosed as children and no ADHD adults ages 60-77 were diagnosed as children. Remember that these people grew up in the 1950s and 1960s when ADHD was rarely identified and then only in the most hyperactive/impulsive and disruptive males.

 

I believe that ADHD in older adults will become the next clinical frontier. While there is some research beginning to accumulate to support identifying and treating this population, the relative absence of trained ADHD clinicians for this population means many unidentified older adults will be diagnosed inaccurately with age related cognitive disorders. To exemplify this likelihood, a U.S. study canvassing memory clinics demonstrated that only 1 in 5 clinics currently screen for ADHD. Therefore, older adults with ADHD are not identified and offered effective ADHD medication and treatment. The result may be ineffective treatment, unnecessary increased medical costs, and the decline in quality of life.

 

For those of you reading this blog, I would encourage you to consider ADHD in older adults whose cognitive complaints have been long-standing, whose negative consequences and impairments echo an ADHD life course, and in whom a first degree relative has ADHD.

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

Stephen V. Faraone, PhD on August 4, 2016

There is a growing interest (and controversy) about ‘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 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 b 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 ADHD used 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 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 ADHD 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 the 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.

 

REFERENCES
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:Results from 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 does not 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 Age at Onset Criterion for Diagnosing ADHD in DSM-5.” J Atten Disord.
Faraone, S. V. and J. Biederman (2016). “Can Attention-Deficit/Hyperactivity Disorder Onset Occur in Adulthood?” JAMA Psychiatry.
Larsson, H., H. Anckarsater, M. Rastam, Z. Chang and P. Lichtenstein (2012). “Childhood attention-deficit hyperactivity disorder as an extreme of a continuous trait: a quantitative genetic study of 8,500 twin pairs.” J Child Psychol Psychiatry 53(1): 73-80.

Lecendreux, M., E. Konofal, S. Cortese and S. V. Faraone (2015). “A 4-year follow-up of attention-deficit/hyperactivity disorder in a population sample.” J Clin Psychiatry 76(6): 712-719.

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