Eight Pictures Describe Brain Mechanisms in ADHD

Apr 11, 2017 | Research Updates

Stephen Faraone, Ph.D. Professor of Psychiatry SUNY Upstate Medical University

When my colleagues and I wrote our “Primer” about ADHD, http://rdcu.be/gYyV, the topic of brain mechanisms was a top priority. Because so much has been written about the ADHD brain, it is difficult to summarize. Yet we did it with the eight pictures reproduce here in one Figure. A quick overview of this Figure shows you the complexity of ADHD’s pathophysiology. There is no single brain region or neural circuit that is affected. Figures (a) and (b) show you the main regions implicated by structural and functional neuroimaging studies. As (c) shows, these regions are united by neural networks rich in noradrenalin (aka, norepinephrine) and dopamine, two neurotransmitters whose activity is regulated by medications that treat ADHD. Figure (d) describes two functional networks. The Executive Control network is, perhaps, the best described network in ADHD. This network regulates behavior by linking dorsal striatum with the dorsolateral prefrontal cortex. This network is essential for inhibitory control, self-regulation, working memory and attention. The Corticocerebellar network is a well-known regulator of complex motor skills. Data also suggest it play a role in the regulation of cognitive functions. Figure (d) describes the Reward Networks of the brain that link ventral striatum with prefrontal cortex. This network regulates how we experience and value rewards and punishments. In addition to its involvement in ADHD, this network has also been implicated in substance use disorders, for which ADHD persons are at high risk. Figures (f) (g) and (h) complete the puzzle with additional regions implicated in ADHD whose role is less well understood. One role for these regions is in the regulation of the Default Mode Network, which controls what the brain does when it is not focused on any specific task (e.g., daydreaming, mind wandering). People differ in the degree to which they shift between the default mode network and networks like Reward or Executive Control, which are active when we engage the world. Recent data suggest that the brains of ADHD people may be in ‘default mode’ when they ought to be engaged in the world.

REFERENCE
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20 ; http://rdcu.be/gYyV

Efficacy of Cognitive Behavioral Therapy With and Without Medication for Adults With ADHD

Apr 6, 2017 | Research Updates

Blog by Mariya Cherkasova, Ph.D., VCH Research Institute

ADHD in adulthood goes hand in hand with problems in key areas daily living, such as work, family life, and social / interpersonal functioning. These are often accompanied by emotional problems, such as depression, anxiety, anger and low self-esteem. Such difficulties may stem from poor skills in organization, time management, planning, and emotion regulation. Cognitive behavioural therapy (CBT) – an established treatment for many psychological problems – has more recently emerged as a promising treatment for adults with ADHD. Cognitive behavioural treatments for adults with ADHD are specifically tailored to addressing their key problem areas and developing skills and compensatory strategies to foster needed improvements. Randomized clinical trials have found such treatments to be efficacious [1, 2], however they have mostly been carried out in groups of medicated patients or in mixed groups of medicated and unmedicated patients. Hence, it has remained unclear whether CBT should be used in combination with medication or whether it can also be an effective standalone treatment for those adults who cannot or do not wish to be medicated.

In our randomized trial, we had therefore set out to compare the effects of a group CBT treatment for adults with ADHD administered alone versus in combination with stimulant medication. The CBT focused on key problem areas for adults with ADHD, such as goal attainment, executive functioning (organization, time management, planning), self-esteem, emotion regulation, impulse control, and relationships. Skills and strategies were covered in session and implemented and practiced as “homework”. To aid with skill practice and implementation, each patient was assigned a coach (mostly junior staff, such as research assistants). The coaches phoned the patients twice a week for 10-15 minutes to help them stay on track with their “homework”. This was a unique feature of our protocol.

At the end of the 12-week treatment, we found that the combined treatment outperformed CBT alone in terms of improvement in ADHD symptoms, organizational skills and self-esteem. However, differences in outcomes between the treatments diminished in these areas over the 6-month following CBT: those who had received CBT alone continued improving over the follow-up, while those who had received the combined treatment maintained their gains. The continued improvement in the CBT alone group was reminiscent of a sleeper effect sometimes seen in psychotherapy studies [3]. We suspect that it may have been fostered by the coaching that continued over the follow-up phase. Coaching was rated as a highly helpful component of the program in feedback evaluations, and we believe that it warrants further study as a component of CBT for ADHD. It is not clear why the patients who underwent the combined treatment did not experience the same continued improvement. As one possibility, they may have reached their full improvement potential by the end of the 12-week treatment, as the combined treatment produced more rapid gains. We conclude that, while the combined treatment produces greater, more immediate benefits, similar levels of improvement may be reached more gradually with CBT alone – at least in the presence of continued coaching support [4].

References
1. Safren, S.A., et al., Life impairments in adults with medication-treated ADHD. J Atten Disord, 2010. 13(5): p. 524-31.
2. Solanto, M.V., et al., Efficacy of meta-cognitive therapy for adult ADHD. Am J Psychiatry, 2010. 167(8): p. 958-68.
3. Bell, E.C., D.K. Marcus, and J.K. Goodlad, Are the parts as good as the whole? A meta-analysis of component treatment studies. J Consult Clin Psychol, 2013. 81(4): p. 722-36.
*4. Cherkasova, M. V., et al. , Efficacy of cognitive behavioral therapy with and without medication for adults with ADHD: A randomized clinical trial. J Atten Disord, 2016. Online ahead of print
*Article reviewed in this blog.

Changing ASD-ADHD Symptom Co-Occurrence Across the Lifespan With Adolescence as Crucial Time Window: Illustrating the Need to go Beyond Childhood

Mar 28, 2017 | Research Updates

*Commentary by Dr. Margaret Weiss: Early identification and intervention has been a hallmark of ASD treatment. The demand for independent social functioning, abstraction and executive functioning peaks in early adolescence. Early intervention during adolescence and young adulthood for comorbid high functioning ASD/ADHD may be critical to optimizing the potential for successful adult functioning.

Changing ASD-ADHD symptom co-occurrence across the lifespan with adolescence as crucial time window: illustrating the need to go beyond childhood Hartman CA, Geurts HM, Franke B, Buitelaar JK, Rommelse NN.
Neurosci Biobehav Rev. 2016 Sep 11. pii: S0149-7634(16)30116-6. doi: 10.1016/j.neubiorev.2016.09.003. [Epub ahead of print]

Abstract
Literature on the co-occurrence between Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) is strongly biased by a focus on childhood age. A review of the adolescent and adult literature was made on core and related symptoms of ADHD and ASD. In addition, an empirical approach was used including 17,173 ASD-ADHD symptom ratings from participants aged 0 to 84 years. Results indicate that ASD/ADHD constellations peak during adolescence and are lower in early childhood and old age. We hypothesize that on the border of the expected transition to independent adulthood, ASD and ADHD co-occur most because social adaptation and EF skills matter most. Lower correlations in childhood and older age may be due to more diffuse symptoms reflecting respectively still differentiating and de-differentiating EF functions. We plea for a strong research focus in adolescence which may -after early childhood- be a second crucial time window for catching-up pattern explaining more optimal outcomes. A full lifespan approach into old age.
* Abstracts are selected for their clinical relevance by Dr. Margaret Weiss MD PhD FRCP, Margaret Weiss MD PhD FRCP(C), Director, Child and Adolescent Psychiatry; Child Study Centre, Little Rock, AR. Her commentary reflects her own opinion, is not approved, or necessarily representative, of the opinion of the CADDRA board.

ADHD Across the Lifespan: Adult Academic Outcomes of Childhood ADHD

Mar 22, 2017 | Research Updates

Betsy Busch, M.D., F.A.A.P. Tufts University School of Medicine

Childhood ADHD is known to persist into adolescence and adulthood in 40-70% of patients. However, its presentation changes with age; symptoms of hyperactivity become less prominent, while difficulties with attention and impulsivity may remain, and executive function problems become increasingly important . Due to this evolving presentation, those with a childhood history of ADHD may not meet full ADHD diagnostic criteria, as adults. Yet, even high-functioning individuals who perform adequately on neuropsychological testing may continue to experience executive dysfunction, emotional dysregulation, and psychosocial impairment in their personal and professional lives. Over the last decade, longitudinal follow-up studies of clinic-referred adults who had childhood ADHD have begun to characterize the deleterious effects of childhood ADHD on adult functioning in various domains.

Jessica Uno, B.A., M.A.
Keck School of Medicine of USC

Recently, Voigt and colleagues from the Barbaresi group recently published the first prospective, population-based study documenting adult academic outcomes among patients with research-identified (including DSM-IV diagnostic criteria) childhood ADHD versus non-ADHD referents . The study sample, drawn from a 1976 to 1982 birth cohort, was unique in that 1) both ADHD and No-ADHD study subjects were members of a population-based sample, not clinic-referred individuals; 2) the subjects’ lifetime medical and school records were available to the investigators; and 3) the Barbaresi group has followed this birth cohort for over 15 years.

For this follow-up study, an academic achievement battery was administered to 232 young adults (mean age 27 years) with research-identified ADHD and 335 referents (mean age 28 years) from the birth cohort. The battery included tests of basic reading, vocabulary, passage comprehension, and arithmetic. After controlling for age, sex, comorbid learning disability status, and maternal education level, Voigt, et al. found that participants with childhood ADHD scored 3 to 5 grade equivalents lower on all academic tests, compared with their non-ADHD peers. All findings had moderate-to-large effect sizes (Cohen’s d= -.55 to -.82).

Interestingly, only 68 of the 232 (29%) participating childhood ADHD cases met the DSM-IV diagnostic criteria for adult ADHD. Yet, there was no significant difference in test scores between childhood ADHD cases with remitted and persistent ADHD, even after controlling for the presence of a co-morbid learning disability (LD). Voigt, et al. believe that this lack of difference indicates that ADHD alone is responsible for the poorer acquisition of academic skills during childhood and adolescence. Academic underachievement in math and reading is strongly associated with lower academic motivation, shorter duration of education, and longer-term socioeconomic adversity, as Biederman and Faraone demonstrated, over a decade ago4. Consistent with their findings, Voigt’s study highlights ADHD as an independent risk factor for poor long-term academic outcomes, predicting far-reaching challenges for adult well-being.

Regarding potential interventions, Voigt, et al. suggest that their findings demonstrate that early and continuous academic interventions for ADHD should be the norm for students with ADHD, since it has a chronic course and long-term consequences, even in those whose ADHD eventually remits. Unfortunately, very few students with ADHD get more than in-class accommodations, under Section 504 of the Rehabilitation Act. While ADHD can qualify many children for specific remedial academic instruction with an Individualized Educational Plan (IEP), when ADHD is considered under the “Other Health Impairment” category of disabilities, few children with ADHD actually receive these services, unless they have a comorbid LD. Based on the positive outcomes from remedial tutoring and teaching of strategies to cope with executive dysfunction demonstrated by other studies, Voigt, et al. advocates for the more frequent inclusion of students with ADHD in formal remedial education programs. Other studies suggest that long-term treatment with stimulant medication can protect many children with ADHD from repeating a grade, and may even protect some from some of ADHD’s common psychiatric comorbidities5. Both pharmacotherapy and educational intervention are likely to produce the best outcomes.

Voigt, et al.’s findings also suggest another mechanism for the association between ADHD and poorer adult outcomes. If childhood ADHD interferes with the acquisition of foundational academic skills, perhaps it also hinders the development of other life skills important to navigating adulthood successfully. With so much at stake, it becomes crucial for patients diagnosed with ADHD as children to receive adequate and ongoing multimodal treatments, with adjustments over time as new challenges appear. Multiple interventions and careful follow-up throughout the lifespan must become the norm in the treatment of those with ADHD, as it is for all other chronic medical disorders.

References:
1. Faraone SV, Asherson P, Banaschewski T, Biederman J, Buitelaar JK, Ramos-Quiroga JA, Rohde LA, Sonuga-Barke EJS, Tannock R, Franke B. Attention-deficit/hyperactivity disorder. Nature Reviews Disease Primers 2015; Aug 6: 15020.
2. Torralva T, Gleichgerrcht E, Lischinsky A, Roca M, Manes F. “Ecological” and Highly Demanding Executive Tasks Detect Real-Life Deficits in High-Functioning Adult ADHD Patients. Journal of Attention Disorders 2012; 17(1): 11–19.
3. Voigt RG, Katusic SK, Colligan RC, Killian JM, Weaver AL, Barbaresi WJ. Academic Achievement in Adults with a History of Childhood Attention-Deficit/Hyperactivity Disorder. Journal of Developmental & Behavioral Pediatrics 2017; 38(1): 1–11.
4. Biederman J, Faraone SV. The effects of attention-deficit/hyperactivity disorder on employment and household income. MedGenMed 2006; 8(3): 12.
5. Biederman J, Monuteaux MC, Spencer T, Wilens TE, Faraone SV. Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics 2009; 124(1): 71-78.

Stimulant Diversion Rising with Young Adults with ADHD

Mar 17, 2017 | Research Updates

David Giwerc, MCAC, MCC

Stimulant diversion, which can range from giving a friend a single pill to selling one’s prescribed pills to others, is on the rise; and young adults, particularly college students, are the primary source of this increasing and troubling form of prescription medication misuse.

Nonmedical use of psychoactive stimulant medication for ADHD is a growing trend within the overarching concern about prescription drug misuse among young adults, most notably college students.¹ Diversion rates for prescribed stimulants was 61.7% in one study.

Prevalence rates of nonmedical use on college campuses are on the rise. Stimulant-related emergency department visits have increased threefold in recent years².

However, despite this steep rise in drug diversion, prescribing physicians who treat ADHD have relatively few clinical strategies for management of this pervasive problem in fact, the non-medical use of prescription drugs in general, with attention on the stimulants are the focus of research by NIDA.

Brooke Molina, PhD., of the University of Pittsburgh, presented preliminary findings during a research symposium on college students with ADHD at the 2017 APSARD Conference. She cited research indicating a significant upsurge in the diversion of prescription stimulant medications, specifically among young adults in college and in treatment for ADHD. In addition to the public health concerns related to this trend, she noted that college students with ADHD may not be prepared for the social pressures placed on them to share their medications as well as the potential consequences for doing so, including legal penalties and their standing in school. It is important to note that drug diversion is considered drug trafficking and applies to the illegal distribution of prescription drugs, including stimulant medications. Under federal and state laws drug trafficking is a felony.

Dr. Molina noted a relative lack of strategies for addressing the growing problem of stimulant diversion among college students. Her research project team is developing and testing practical strategies targeted to effectively communicate the dangers/consequences of drug diversion to primary care providers and college patients who may not be aware of the consequences of giving away or selling their prescription stimulant medication to a fellow student.

In addition to the study and dissemination of the sorts of educational programs, there are initial steps that can be taken by prescribing physicians as well as psychosocial clinicians who treat college students with ADHD. Drawing from the sorts of strategies in Dr. Molina’s program, the first step is preparing students with ADHD that they will likely be approached at some point about sharing or selling their stimulant medications.
Information can be shared about the risks in terms of potential legal culpability and the fact that expulsion from college is a possible consequence if they would be caught diverting medications. In fact, encouraging college patients to not publicize the fact that they take prescribed medications in the first place, or at least making sure that they keep their medications in some sort of locked container is a step that decreases the likelihood of facing peer pressure or the chance that their pills are at risk for theft. Lastly, anticipating and rehearsing some scenarios in which a student imagines they might feel pressured to share medications is a way to practice what to say in advance rather than figuring out what to say on the spot.

Despite these problems with diversion, the pharmacologic treatment of ADHD among college students continues to be important. Effective treatment allows these students, many of whom in previous decades would not have been identified with ADHD and therefore unable to get into college, to be able to manage their symptoms, demonstrate their skills, and pursue their goals. By taking a few extra moments to counsel students who are taking prescribed medications for ADHD about the risks of diversion, perhaps this disturbing trend can start to be reversed.

References
¹Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: A systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008;47:21–31.
² Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. (January 24, 2013). The DAWN Report: Emergency Department Visits Involving Attention Deficit/Hyperactivity Disorder Stimulant Medications. Rockville, MD.