Joseph_Biederman_AIA_rX8AEq.png.jpgThis blog addresses the relationship between executive function deficits in general and working memory (WM) deficits in particular and attention-deficit/hyperactivity disorder (ADHD). Although some neuropsychological models of ADHD have proposed that ADHD arises from deficits in executive functions, accumulating clinical evidence show that it afflict some but not all individuals with ADHD and suggests that ADHD and executive function deficits represent separate clinical condition. Because executive functions refer to a wide and diverse group of high order mental functions, one approach to evaluate this important issue is to focus on one prominent facet of executive functions, mainly working memory. Working memory (WM) refers to a key brain system that provides temporary storage and manipulation of information essential for adequate cognitive functioning. It focuses attention, inhibits irrelevant stimuli, recognizes priority patterns and hierarchies and selects the goals that are best suited to solving a problem. Since these cognitive processes are critical for learning, their impairment can lead to deficits in functioning including social and educational dysfunction, low educational achievement and can have a serious impact on educational success. To address this issue we examined referred youth with and without ADHD with and with without WM deficits in functional, social and academic outcomes. We used Resting State FMRI imaging to examine whether the neural circuits subserving WM deficits overlap with those of ADHD. We investigated this issue in preclinical studies where we examined spatial WM and dopamine receptor activity in rodents. In human studies, we examined whether the most standard treatment for ADHD has a different effect on measures of WM and ADHD. This body of research provides evidence for a clinical, pharmacological and neurobiological dissociation between ADHD and WM deficits. Our preclinical findings demonstrate that the magnitude of improvement in WM produced by the D4 receptor agonist is significantly greater than that produced by methylphenidate. Our human treatment study with methylphenidate provide evidence for very different effects for ADHD and WM deficits Our clinical studies show that significantly more youth with ADHD had WM deficits than controls (31.9% vs. 13.7%) and their presence is significantly and specifically associated with academic failure. In our imaging study, we found that brain activations to a WM test were different in subjects with ADHD with associated WM deficits compared to controls and ADHD subjects without WM deficits. This body of work indicates that WM deficits afflict a minority of subjects with ADHD and when present they significantly and selectively increase the risk for academic dysfunction in subjects with ADHD, they have separate neural underpinning, and respond differently to treatments for ADHD. Screening for WM deficits may help identify individuals with ADHD at high risk for academic dysfunction.
 

References
K. P. LEE, N. PINEDA, T. BRUNE, K. PATEL, A. GANNON, T. J. SPENCER, J. BIEDEMAN, P. G. BHIDE, J. ZHU. Hyperactivity and working memory deficits induced by prenatal nicotine exposure are associated with dopamine D1 and D4 receptor dysfunction. Society for Neuroscience Annual Meeting, Washington, DC, November, 2014.
Fried R, Chan J, Feinberg L, Pope A, Woodworth KY, Faraone SV, et al. Clinical correlates of working memory deficits in youth with and without ADHD: A controlled study. Journal of clinical and experimental neuropsychology. 2016;38(5):487-96.

Mattfeld AT, Whitfield-Gabrieli S, Biederman J, Spencer T, Brown A, Fried R, et al. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain. NeuroImage Clinical. 2016;10:274-82.
Biederman J, Chan J, Spencer TJ, Woodworth KY, Kenworthy T, Fried R, Bhide P, Faraone SV. Evidence of a pharmacological dissociation between the robust effects of methylphenidate on ADHD symptoms and weaker effects on working memory. Journal of Brain Sciences. 2015; 1(2): 43-53.

Joseph Biederman AIA rX8AEq
This blog addresses the relationship between executive function deficits in general and working memory (WM) deficits in particular and attention-deficit/hyperactivity disorder (ADHD). 

Although some neuropsychological models of ADHD have proposed that ADHD arises from deficits in executive functions, accumulating clinical evidence show that it afflicts some but not all individuals with ADHD and suggests that ADHD and executive function deficits represent separate clinical conditions.

Because executive functions refer to a wide and diverse group of high order mental functions, one approach to evaluate this important issue is to focus on one prominent facet of executive functions, mainly working memory. Working memory (WM) refers to a key brain system that provides temporary storage and manipulation of information essential for adequate cognitive functioning.  It focuses attention, inhibits irrelevant stimuli, recognizes priority patterns and hierarchies and selects the goals that are best suited to solving a problem.

Since these cognitive processes are critical for learning, their impairment can lead to deficits in functioning including social and educational dysfunction, low educational achievement and can have a serious impact on educational success. 

To address this issue we examined referred youth with and without ADHD, and with and without WM deficits in functional, social and academic outcomes. We used Resting State FMRI imaging to examine whether the neural circuits subserving WM deficits overlap with those of ADHD.  We investigated this issue in preclinical studies where we examined spatial WM and dopamine receptor activity in rodents.  Our preclinical findings demonstrate that the magnitude of improvement in WM produced by the D4 receptor agonist is significantly greater than that produced by methylphenidate.

CBT treats Executive Dysfunction Free ADHD CME WyUaeE
In human studies, we examined whether the most standard treatment for ADHD has a different effect on measures of WM and ADHD. This body of research provides evidence for a clinical, pharmacological and neurobiological dissociation between ADHD and WM deficits.  Our human treatment study with methylphenidate provided evidence for very different effects for ADHD and WM deficits Our clinical studies show that significantly more youth with ADHD had WM deficits than controls (31.9% vs. 13.7%) and their presence is significantly and specifically associated with academic failure.

In our imaging study, we found that brain activations to a WM test were different in subjects with ADHD with associated WM deficits compared to controls and ADHD subjects without WM deficits.

This body of work indicates that WM deficits afflict a minority of subjects with ADHD and when present they significantly and selectively increase the risk for academic dysfunction in subjects with ADHD, they have separate neural underpinning, and respond differently to treatments for ADHD.

Screening for WM deficits may help identify individuals with ADHD at high risk for academic dysfunction.

 

References

P. LEE, N. PINEDA, T. BRUNE, K. PATEL, A. GANNON, T. J. SPENCER, J. BIEDERMAN, P. G. BHIDE, J. ZHU. Hyperactivity and working memory deficits induced by prenatal nicotine exposure are associated with dopamine D1 and D4 receptor dysfunction. Society for Neuroscience Annual Meeting, Washington, DC, November, 2014

Fried R, Chan J, Feinberg L, Pope A, Woodworth KY, Faraone SV, et al. Clinical correlates of working memory deficits in youth with and without ADHD: A controlled study. Journal of clinical and experimental neuropsychology. 2016;38(5):487-96.

Mattfeld AT, Whitfield-Gabrieli S, Biederman J, Spencer T, Brown A, Fried R, et al. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain. NeuroImage Clinical. 2016;10:274-82.

Biederman J, Chan J, Spencer TJ, Woodworth KY, Kenworthy T, Fried R, Bhide P, Faraone SV. Evidence of a pharmacological dissociation between the robust effects of methylphenidate on ADHD symptoms and weaker effects on working memory. Journal of Brain Sciences. 2015; 1(2): 43-53.

 

 

 

Joseph Biederman MD ADHD in Adults

Is ADHD Always a Childhood Onset Disorder?

by Joseph Biederman, MD – August 4, 2016

Recent population based studies raise the intriguing question as to whether adult ADHD is always preceded by childhood onset of symptoms or can develop anew in adult life. From Brazil, one group argues that child and adult ADHD are “distinct syndromes”; from the United Kingdom (UK), another group states that adult ADHD is “more complex than a straightforward continuation of the childhood disorder” and from New Zealand (NZ), a third group claimed that adult ADHD is “not a neurodevelopmental disorder”.

In each study, adult onset ADHD refers to cases in which full-threshold ADHD had not been diagnosed by the investigators at prior assessments. In the NZ study, compared with controls, the adult onset ADHD group had more teacher-rated symptoms of ADHD, more conduct disorder (CD) in childhood and were more likely to have had a combined parent/teacher report of ADHD symptom onset prior to age 12. (DSMV recognizes onset of ADHD until the age of 12.) Likewise, the adult onsets in the UK study had high rates of ADHD symptoms, CD and oppositional defiant disorder (ODD) in childhood. Thus, many “adult onsets” of ADHD cases appear to have neurodevelopmental roots.

DSM V Guide to ADHD Diagnosis downloadBecause population studies use non-referred samples, those being diagnosed may not be self-aware of their symptoms, which increases the risk of false negatives. In population studies the ability of the subject to report on his or her own symptoms is critical since it requires insight and self awareness. It has been well documented that youth with ADHD are very poor reporters of their own symptoms. Such difficulties can certainly extend to adult years. Consistent with this idea, 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.4 Thus, the UK, Brazilian and NZ studies may have underestimated the persistence of ADHD and overestimated the prevalence of adult onsets. In contrast, self awareness is not an issue for subjects referring themselves to clinical care since, by definition, it is their self awareness that brings them to the clinic.

These reports do very little to help clarify whether these “adults” do not recall childhood symptoms, are unable to report on them, or are unable to distinguish onset of symptoms form onset of symptoms-associated impairments that may account for the different ages of onset. In these cases, the onset of symptoms and impairment could be separated by many years, particularly among those with strong intellectual abilities and those living in supportive, well-structured childhood environments. Such intellectual and social scaffolding would help ADHD youth to compensate in early life, only to decompensate into a full ADHD syndrome when the scaffolding is removed.

Such an interpretation would suggest that the etiology of ADHD leads to a wide variability in age at onset of initial symptoms, symptoms exceeding diagnostic threshold and impairment arising from those symptoms. Such variability is accepted for many other medical disorders. It is also consistent with the idea that ADHD is the extreme and impairing tail of a continuum. This view of posits that ADHD symptoms and ADHD impairment emerge due to the accumulation of environmental and genetic risk factors. Those with lower levels of risk at birth will take longer to accumulate sufficient risk factors and longer to onset with symptoms and impairment. Yet, because these effects are multifactorial, there is no clean separation of etiologic factors in people above and below a certain age.

In this context it is important to remember that the age of onset of ADHD of 12 years proposed in DSM-V, while an improvement from the previous age of onset of 7 years, is still completely arbitrary, creating the immediate dilemma on how to diagnose patients who have an onset of symptoms after 12 years of age. Such a scenario may suggest that ADHD may be a disorder with a continuum of ages of onset, with some subjects starting their symptoms earlier while others later.

These concerns do not argue against the existence of adult onset ADHD or the idea that it is a clinically relevant syndrome. In fact, as a group, the adult onset cases showed significant functional impairments. Moreover, some of the studies ruled out the idea that adult onset ADHD is a misdiagnosis of another disorder. Further support for the validity of adult onset ADHD comes from a study of referred adults who retrospectively reported childhood symptoms 5. Based on clinical features and familial transmission, that study concluded that onsets of ADHD in late adolescence and early adulthood were valid.5

See: http://archpsyc.jamanetwork.com/article.aspx?articleID=2522743

ADHD Consensus Statement download

 

 

 

REFERENCES
1. Faraone S, Biederman J, Mick E. The Age Dependent Decline Of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis Of Follow-Up Studies. Psychological Medicine. 2006;36(2):159-165.
2. Moffitt TE, Houts R, Asherson P, et al. Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study. Am J Psychiatry. 2015:appiajp201514101266.
3. Fayyad J, De Graaf R, Kessler R, et al. Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. Br J Psychiatry. 2007;190:402-409.
4. Sibley MH, Pelham WE, Molina BS, et al. When diagnosing ADHD in young adults emphasize informant reports, DSM items, and impairment. J Consult Clin Psychol. 2012;80(6):1052-1061.
5. Chandra S, Biederman J, Faraone S. Assessing the Validity of the Age at Onset Criterion for Diagnosing ADHD in DSM-5. Journal of attention disorders. In Press.
6. Lecendreux M, Konofal E, Cortese S, Faraone SV. A 4-year follow-up of attention-deficit/hyperactivity disorder in a population sample. J Clin Psychiatry. 2015;76(6):712-719.
7. Asherson P, Trzaskowski M. Attention-deficit/hyperactivity disorder is the extreme and impairing tail of a continuum. J Am Acad Child Adolesc Psychiatry. 2015;54(4):249-250.