http://medicalwritingtraining.com/The term “cognitive behavior therapy (CBT)” refers to a type of talk therapy that seeks to change the way patients think about themselves, their disorder and the world around them in a manner that will help them overcome symptoms and achieve life goals. Because CBT is typically administered by a psychologist or other mental health professionals, CBT services are not available in primary care. Nonetheless, it is useful for primary care practitioners to know about CBT so that they can refer appropriately as needed. So, what can we say about the efficacy of CBT for treating adults with ADHD. Based on a meta-analysis by Young and colleagues, we know for certain that the number of published trials of CBT for adult ADHD is small; only nine trials are available. Five of these compared CBT with waiting list controls; three compared CBT with appropriate placebo control groups. In all of these studies, patients in the CBT and control groups were also being treated with ADHD medications. Thus, they speak to the efficacy of CBT when given as an adjunctive treatment. The meta-analysis examined the waiting list controlled studies and the placebo controlled studies separately. For both types of study, the effect of CBT in reducing ADHD symptoms was statistically significant, with a standardized mean effect size of 0.4. This effect size, albeit modest, is large enough to conclude that CBT will be useful for some patients being treated with ADHD medications. Given these results, a reasonable guideline would be to refer adults with ADHD to a CBT therapist if they are being maintained on an ADHD medication but that medication is not leading to a complete remission of their symptoms and impairments. So listen to your patients. If, while on an appropriately titrated medication regime, they still complain about unresolved symptoms or impairments you need to take action. In some cases, changing their dose or shifting to another medication will be useful. If such approaches fail or are not feasible, you should consider referral to a CBT therapist.
 

REFERENCE
Young, Z., Moghaddam, N. & Tickle, A. (2016). The Efficacy of Cognitive Behavioral Therapy for Adults With ADHD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Atten Disord.

http://medicalwritingtraining.com/Over the past few decades, a consensus has emerged among psychopathologists that some patients exhibit a well-defined syndrome referred to as sluggish cognitive tempo or SCT. There are no diagnostic criteria for SCT because it has not yet been accepted as a separate disorder by the American Psychiatric Association. People with SCT are slow-moving, indolent and mentally muddled. They often appear to be lost in thoughts, daydreaming, drowsy or listless. In reviewing these symptoms and the literature, Barkley suggested that SCT be referred to as Concentration Deficit Disorder (CDD). This term is less pejorative but is not yet commonly used. Becker and colleagues recently evaluated the internal and external validity of SCT via a meta-analysis of 73 studies. Internal validity addresses the consistency of SCT symptoms as measure of an underlying construct. Based on factor analytic studies using more than 19,000 participants, the authors concluded that the items purported to measure SCT are sufficiently correlated with one another to justify the idea that they measure the same underlying construct. Further support for internal validity was found in studies reporting high test-retest and interrater reliability. As regards ADHD, the authors found that SCT correlated significantly with both inattentive (r = 0.72) and hyperactive-impulsive (r = 0.46) symptoms in adults. The greater correlation with inattentive symptoms makes sense given the nature of SCT symptoms. So these data confirm two key points about SCT: 1) it is definitely associated with ADHD symptoms and 2) it is a meaningful construct in its own right. Very little is known about the implications of SCT for the treatment of ADHD. In a naturalistic study of 88 children and adolescents with ADHD, Ludwig and colleagues examined the effect of SCT on the response of ADHD symptoms to methylphenidate. They found no significant differences in treatment response between subjects with and without SCT. McBurnett and colleagues tested the effects of atomoxetine on SCT in children with ADHD and dyslexia (ADHD+D) or dyslexia only. Atomoxetine treatment led to significant reductions in both ADHD symptoms and SCT outcomes. Because controlling for changes in ADHD symptoms did not predict changes in SCT outcomes, the authors concluded that change in SCT in response to atomoxetine is mostly independent of change in ADHD. Although these data are preliminary and in need of replication, they do provide some guidance for clinicians dealing with ADHD patients who also have SCT.
 

REFERENCE
Becker, S. P., Leopold, D. R., Burns, G. L., Jarrett, M. A., Langberg, J. M., Marshall, S. A., McBurnett, K., Waschbusch, D. A. & Willcutt, E. G. (2016). The Internal, External, and Diagnostic Validity of Sluggish Cognitive Tempo: A Meta-Analysis and Critical Review. J Am Acad Child Adolesc Psychiatry 55, 163-78.

Ludwig, H. T., Matte, B., Katz, B. & Rohde, L. A. (2009). Do sluggish cognitive tempo symptoms predict response to methylphenidate in patients with attention-deficit/hyperactivity disorder-inattentive type? J Child Adolesc Psychopharmacol 19, 461-5.

McBurnett, K., Clemow, D., Williams, D., Villodas, M., Wietecha, L. & Barkley, R. (2016). Atomoxetine-Related Change in Sluggish Cognitive Tempo Is Partially Independent of Change in Attention-Deficit/Hyperactivity Disorder Inattentive Symptoms. J Child Adolesc Psychopharmacol.

Barkley, R. A. (2014). Sluggish cognitive tempo (concentration deficit disorder?): current status, future directions, and a plea to change the name. J Abnorm Child Psychol 42, 117-25.

Stephen_Faraone_PhD_AIA_2016_XM7MQd.png.jpgAdults with ADHD are more likely to have accidents, to drive unsafely, to have unsafe sex and to abuse substances. These ‘real world’ impairments suggest that people with ADHD may be predisposed to making risky decisions. Many studies have attempted to address this but is only recently that their results have been aggregated into a systematic review and meta-analysis. This paper by Dekkers and colleagues reports of 37 laboratory studies of risky decision making that studied a total of 1175 ADHD patients and 1222 controls. In these laboratory tasks, research participants are given a task to complete which require that they make choices which have varying degrees of risk and reward. Using the results of such experiments, researchers can score the degree to which participants make risky decisions. When Dekkers and colleagues analyzed the 37 studies together, they found substantial evidence that ADHD people are more likely to make risky decisions than people without ADHD. The tendency to make risky decisions was greatest for those who, in addition to having ADHD, also had conduct or oppositional disorders, which both have features that indicate antisocial behavior and aggressiveness. We cannot tell from these studies why ADHD patients make risky decisions. One explanation is that it is simply the impulsivity of ADHD people that leads to rash, unwise decisions. Another theory postulates that risky decisions reflect deficits in one’s sensitivity to rewards and punishments. If we are very motivated by reward and not aware of or affected by the possibility of punishment, then risky decisions will be common. The studies analyzed in the meta-analysis were not designed to demonstrate a link between risky decision making in the lab and the real world risky decisions that lead to accidents and other outcomes. It is reasonable to hypothesize such a link, which is why clinicians should consider risky decision making when planning treatments. If you suspect deficits in this area, it will not change your approach to pharmacologic treatment but, given the potential adverse consequences of risky decisions, you should consider referring such patients to cognitive behavior therapy for adult ADHD as this talk therapy may be able to teach ADHD adults how to cope with their decision making deficits.
 

REFERENCE
Dekkers, T. J., Popma, A., Agelink van Rentergem, J. A., Bexkens, A. & Huizenga, H. M. (2016). Risky decision making in Attention-Deficit/Hyperactivity Disorder: A meta-regression analysis. Clin Psychol Rev 45, 1-16.

http://medicalwritingtraining.com/One of the many great contributions of Dr. Russell Barkley was his conceptualization of ADHD as a disorder of self-regulation. ADHD people have difficulties regulating their behavior, which lead to the classic diagnostic criteria of hyperactivity and impulsivity and they have problem regulating cognitive processes which leads to the well-known inattentive diagnostic criteria for the disorder. In a 2010 paper, Dr. Barkley argued persuasively that deficient emotional self-regulation should also be considered a core component of ADHD alongside deficient behavioral and cognitive self-regulation. Although the DSM 5 did not add any emotional symptoms to the revised criteria for ADHD a new paper by Graziano and Garcia supports Dr. Barkley’s position. They conducted a meta-analysis of 77 studies of emotional dysregulation that comprised a total of 32,044 participants. They defined emotional dysregulation as the failure to modify emotional states in a manner that promotes adaptive behavior and leads to the success of goal directed activities. They identified three types of emotional dysregulation: emotion recognition and understanding (ERU), emotional reactivity/negativity/lability (ERNL) and empathy/callous-unemotional traits (ECUT). ERU refers to the ability to perceive, process and infer one’s own emotions and the emotions of others. ERNL refers to the intensity and valence of the emotional response. Reactivity refers to the rapidity of the emotional response (e.g., is a person quick tempered rather than reflective); negativity refers to the valence of the emotion. Is it extreme or appropriate to the situation; and lability refers to how quickly emotional states shift or cycle over time. The ECUT dimension has two poles. At one extreme is the empathic person whose reactions are guided by a clear understanding of the emotional states of others. At the other pole is the psychopath who shows little or no emotion to stimuli that evoke strong emotional reactions in the average person. When the data from the 77 studies was sorted into these three categories, the authors found that ADHD people had impairments in all three domains. The magnitude of impairment was a bit greater for ERNL than it was for ECUT and ERU, but not dramatically so. The association between ADHD and these domains of emotional dysregulation increased with increasing age. It is for this reason that some ADHD experts think that emotional dysregulation should be included in the diagnostic criteria for adult ADHD. Because behavioral hyperactivity diminishes with age, these criteria are less sensitive for adult ADHD than they are for child ADHD. Substituting emotional dysregulation items for hyperactivity items could, potentially, improve diagnoses of adult ADHD. Future work will address this issue. In the meanwhile, those who screen and diagnose adult ADHD should be aware that symptoms of emotional dysregulation might be the most prominent for some adults with the disorder.

 
REFERENCE
Barkley, R. A. (2010). Deficient Emotional Self-Regulation: A Core Component of Attention-Deficit/Hyperactivity Disorder. Journal of ADHD and Related Disorders 1, 5-37.

Graziano, P. A. & Garcia, A. (2016). Attention-deficit hyperactivity disorder and children’s emotion dysregulation: A meta-analysis. Clin Psychol Rev 46, 106-23.

Stephen_Faraone_PhD_ADHD_in_Adults
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.

 

http://medicalwritingtraining.com/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.

http://medicalwritingtraining.com/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.

http://medicalwritingtraining.com/Adult Onset ADHD: Does it Exist? Is it Distinct from Youth Onset ADHD? 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.
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. St Clair, 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 disorders estimated from genome-wide SNPs.” Nat Genet 45(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). “When diagnosing ADHD in young adults emphasize informant reports, DSM items, and impairment.” J Consult Clin Psychol 80(6): 1052-1061.

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

by Stephen V. Faraone, PhD – August 4, 2016

Stephen V Faraone, PhD, ADHD in AdultsThere 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.

ASRS Professional Screener DownloadThe 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.

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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.

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. St Clair, 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 disorders estimated from genome-wide SNPs.” Nat Genet 45(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). “When diagnosing ADHD in young adults emphasize informant reports, DSM items, and impairment.” J Consult Clin Psychol 80(6): 1052-1061.

http://medicalwritingtraining.com/Suicide is one of the most feared outcomes of any psychiatric condition. Although its association with depression is well known, a small but growing research literature shows that ADHD is also a risk factor for suicidality.

Suicide is difficult to study. Because it is relatively rare, large samples of patients are needed to make definitive statements. Studies of suicide and ADHD must also consider the possibility that medications might elevate that risk.

For example, the FDA placed a black box warning on atomoxetine because that ADHD medication had been shown to increase suicidal risk in youth. A recent study of 37,936 patients with ADHD now provides much insight into these issues (Chen, Q., Sjolander, A., Runeson, B., D’Onofrio, B. M., Lichtenstein, P. & Larsson, H. (2014). Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study. BMJ 348, g3769.). In Sweden, such large studies are possible because researchers have computerized medical registers that describe the disorders and treatments of all people in Sweden. Among 37,936 patients with ADHD, 7019 suicide attempts or completed suicides occurred during 150,721 person years of follow-up. This indicates that, in any given year, the risk for a suicidal event is about 5%.

For ADHD patients, the risk for a suicide event is about 30% greater than for non-ADHD patients. Among the ADHD patients who attempted or completed suicide, the risk was increased for those who had also been diagnosed with a mood disorder, conduct disorder, substance abuse or borderline personality. This is not surprising; the most serious and complicated cases of ADHD are those that have the greatest risk for suicidal events.

The effects of medication were less clear. The risk for suicide events was greater for ADHD patients who had been treated with non-stimulant medication compared with those who had not been treated with non-stimulant medication. A similar comparison showed no effect of stimulant medications.

This first analysis suffers from the fact that the probability of receiving medication increases with the severity of the disorder. To address this problem, the researchers limited the analyses to ADHD patients who had had some medication treatment and then compared suicidal risk between periods of medication treatment and periods of no medication treatment. This analysis found no increased risk for suicide from non-stimulant medications and, more importantly, found that for patients treated with stimulants, the risk for suicide was lower when they were taking stimulant medications. This protective effect of stimulant medication provides further evidence of the long-term effects of stimulant medications which have also been shown to lower the risks for traffic accidents, criminality, smoking and other substance use disorders.