Towards an integrated theory of ADHD (and substance abuse)

1. Towards an integrated theory of ADHD (and substance abuse) Alban Burke November 2010

2. [The brain] ...is bound together in a dynamic system of systems that does millions of different things in parallel. It is probably so complex that will never succeed in comprehending itself. Yet it will never cease to try. (Carter, 1998, p.8)

3. Introduction • Attention Deficit /Hyperactivity disorder (ADHD) is a complex and common disorder with a great variation in its clinical presentation. • It has been historically classified primarily as a childhood disorder and has core symptoms associated with hyperactivity/ impulsivity and inattention. • Research evidence suggests that this disorder has strong neurobiological and genetic underpinnings. • The symptoms associated with ADHD are clinically significant impairment in the social and academic functioning of children with this disorder.

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5. Stimulus • This involves both internal and external events that start a recursive process. • External events are quite self-explanatory, however internal events are often ignored, especially in some quarters of Psychology. • These internal events are important in our ultimate model and they include cortical and sub-cortical hyper- or hypo-arousal as well minor or major physiological events. Footer

6. Organism: • Due to the fact that research on cortical and sub-cortical structures is not limited to humans, we decided on this term as it allows flexibility in accommodating various animal studies. • Various themes are included here, e.g.: • Genetics • Cortical arousal • Sub-cortical structures • Temperament / “personality” • Coping and survival strategies • Perceptual processes • Information processing and memory • Selective and sustained attention • Psychomotor abilities • Executive functions Footer

7. Response: • Typically, and erroneously, responses are often equated to behaviour only, however, it is argued that all responses have conscious or unconscious behavioural, emotional, cognitive and physiological responses. • In this model it is imperative that one investigates, and understands, all responses to an event. • It is maintained that all responses, and their outcomes, are monitored. In effect a response is not a final outcome, but rather a continuous process of reassessment which either results in the maintenance or adjustment of the response hierarchy. Footer

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9. History of cADHD and aADHD Footer

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13. Current status of research: Genetics • Nadder , Silberg, Rutter, Maes and Eaves (2001) did a study in which they explored the phenotypic and genetic interrelationships underlying ADHD. • The ADHD symptomatology was assessed by various instruments in a sample of 735 male and 819 female same-sex twin pairs, aged 8 to 16 years. Multivariate analyses were applied to parental and teacher ratings from an investigator-based interview, the CAPA, and three questionnaires (the CBCL and the Rutter Parent and Teacher Scales). • Results from patterns of intercorrelations and factor analyses of maternal measures suggested that at the phenotypic level, these assessed the same underlying behavioural construct, which differed from other emotional and behavioural constructs. Footer

14. Genetic analyses, however, showed that in addition to a common factor underlying the expression of ADHD as assessed across the range of measures, additional genetic factors were identified that were method- and rater-specific. • The findings suggest that although the investigator-based interview and the behavioural checklists tap similar aspects of ADHD behaviour, there is additional rater-specific variance. • In line with this, Sharp, McQuillin and Gurling (2009) describe ADHD as a clinically and genetically heterogeneous syndrome which is comorbid with childhood conduct disorder, alcoholism, substance abuse, antisocial personality disorder, and a wide array of affective disorders. Footer

15. The common denominator seems to be the dopamine transporter gene (DAT1). Remarkably, and for the first time in psychiatry, genetic markers at the DAT1 locus appear to be able to predict clinical heterogeneity because the non-conduct disordered subgroup of ADHD is associated with DAT1 whereas other subgroups do not appear to be associated. • The second most well replicated susceptibility gene encodes the DRD4 dopamine receptor and many other dopamine related genes appear to be implicated. • It is becoming increasingly clear that genes causing bipolar mania overlap with genes for a subtype of ADHD. • The key to understanding the genetics of ADHD is to accept very considerable heterogeneity with different genes having effects in different families and in different individuals. Footer

16. Current status of research: Neurology, Neuropsychology and Neurophysiology Footer

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20. Imaging data are often confounded by small numbers of patients and sometimes contradictory results. However, recent findings have shown similarities in adult ADHD and ADHD in children, such as the impairment of cerebello-striato-frontal networks. • Consistent imaging findings are in the dysfunction of striatal brain structures and anterior cingulated cortex (Schneider, Retz, Coogan, Thome & Rösler, 2006). • Although the prefrontal cortical structures also seem to play a pivotal role in ADHD psychopathology, these findings are not unique or specific to ADHD. Footer

21. Given that ADHD symptomatology undergoes changes with adulthood in terms of decline of hyperactivity and impulsivity, while disorganization and emotional dysregulation come to the fore, a more focused approach to understanding emotional dysregulation in adult ADHD should reveal insights into the pathophysiology of this condition. • It is important to bear in mind that comparison of results between young children and adults with ADHD could be confounded by maturational or developmental effects with increasing age (Schneider, Retz, Coogan, Thome & Rösler, 2006). Footer

22. Finally, in animal models emerging evidence suggests that methylphenidate alters the dopaminergic system with long-term effects beyond the termination of treatment (Grund, Lehmann, Bock, Rothenberger, & Teuchert-Noodt, 2006). • On the other hand, longterm treatment did not show functional differences after termination of medication compared to treatmentnaïve ADHD patients (Pliszka, Glahn, Semrud-Clikeman, Franklin, Perez, Xiong & Liotti, 2006). • Whether stimulant medication has long-term influence on brain morphology or neuroregenerative effects is not clarified. • Thus, controversies between structural and functional results have still to be resolved. Footer

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24. Sensation seeking: Mediating factor in substance abuse • A study by Faraone, Kunwar, Adamson and Biederman (2009) provides some evidence that those who have been diagnosed with AADHD show specific personality traits such as novelty seeking, harm avoidance, reward dependence, persistence, self-directiveness, cooperativeness and self-transcendence (Faraone et al., 2009). • These personality traits manifest, according to Faraone et al (2006) as follows: Footer

25. Sensation seeking: Mediating factor in substance abuse • High novelty seeking:individuals high in novelty seeking are quick-tempered, curious, easily bored, impulsive, extravagant, and disorderly. • High harm avoidance: People high in harm avoidance are fearful, socially inhibited, shy, passive, easily tired, and pessimistic even in situations that do not worry other people. Although the higher harm avoidance of ADHD subjects is consistent with ADHD’s comorbidity with anxiety disorders and depression (Biederman et al. 2006; Kessler et al. 2006), the group differences Faraone et al (2006) observed were not accounted for by these disorders, which suggests that this personality subscale may tap subclinical traits. • Low persistence: Tendency to give up easily when frustrated, less likely to strive for higher goals, unlikely to persevere at tasks and associated deficits in executive functioning. Low persistence is consistent with the executive functioning deficits seen in many patients with ADHD (Biederman et al. 2007). • Low reward dependence: Practicality, tough-mindedness, social insensitivity and indifference. Footer

26. Sensation seeking: Mediating factor in substance abuse • Low self-directedness: Less responsible, reliable, resourceful, goal-oriented and self-confident than other adults and they find it difficult to define, set and pursue meaningful internal goals. • Low cooperativeness: Self-absorbed, intolerant, critical, unhelpful, and opportunistic and inconsiderate of other people’s rights or feelings. These traits are consistent with ADHD’s co-morbidities with ODD and conduct disorder. • The extreme of normal personality traits, as suggested by the aforementioned study, not only describe a pattern of disruptive behaviour, but also raises many other questions and alternative perspectives on AADHD. • One personality trait which was not investigated by Faraone et al (2003) but may also be related to AADHD, is sensation seeking (the tendency to seek out novel experiences). Footer

27. Sensation seeking: Mediating factor in substance abuse • Research on the neurological and neurophysiological aspects of sensation seeking has yielded some interesting results. • One of these is where brain images showed that when high sensation seekers viewed emotionally arousing photographs, there was increased activity in the brain region known as the insula (See Figure 1a). • This brain structure acts in part as a gateway where visceral signals from the body are first received and interpreted by the brain. In contrast to this, when low sensation seekers looked at arousing photographs, there was increased activity in the frontal cortex area of the brain (See Figure 1b). Footer

28. Sensation seeking: Mediating factor in substance abuse • Regardless of whether the pictures were pleasant (e.g., mild erotica) or unpleasant (e.g., a snake poised to strike), the high-sensation seekers showed early and strong activation in the insula. (See Figure 1a). • In contrast, in the low-sensation seekers, insula activity barely rose above baseline levels. (See Figure 1b.) • Instead, there was pronounced early activity in the anterior cingulate, a part of the cortex strongly linked to the regulation of emotions (and many other things). • In high-sensation seekers, anterior cingulate activation was delayed in relation to the lows, though it eventually reached a similar peak. Footer

29. Sensation seeking: Mediating factor in substance abuse Footer

30. Sensation seeking: Mediating factor in substance abuse • However, not only is there increased activity in certain areas but, in a further study, using urine samples and spinal taps, it was found that high sensation seekers had a significant deficit in levels of a byproduct of the brain chemical norepinephrine. • The findings of the aforementioned study should be viewed together with findings on brain structures, as the two are not mutually exclusive. • Often researchers make the mistake of viewing the causes of pathology or behaviour as being either brain structure, or neurotransmitter based. • However, in this instance we are not considering structural deficits, but rather functional deficits. • Brain activity, in essence, relies on neurotransmitter release. • If one considers that the noradrenergic pathway runs through the frontal and prefrontal cortex (see Figure 2), then altered norepinephrine must have an effect on the activity in these areas. Footer

31. Noradrenergic Serotonergic Dopaminergic Footer

32. Case study • 28 year old female, childhood diagnosis of ADHD, no formal diagnosis of aADHD, no medication. • 15-16 years very anti-drugs, then had boyfriend who smoked cigarettes and maijuana • Started using on weekends out of curiosity, first experience, no effect, thereafter euphoric, and heightened sensation (“supersonic hearring”) • Used it once before school day for the thrill of it • Went to raves where she started using Ecstasy. First experience was total euphoria, thereafter never the same experience and used more to try and regain that first experience • Also reports that her thoughts seemed to be more focussed • Stopped because she became bored of it • Used cocaine a few times, but according to her it had no effect • Anti-smoking and anti-alcohol (father an acloholic) • Smoked Hookah pipe • Now uses Bioplus and Vitamin B tablets because she discovered by accident that it slows her down and helps with her attention and concentration Footer

33. Integrated model • We propose that ADHD children and adults are predisposed to substance abuse. • In our opinion, ADHD sufferers are aware that their behaviour is unacceptable, and this awareness creates discomfort (e.g. 5-year-old:”I don’t want to be like this”). i.e. the symptoms in themselves do not create discomfort (as opposed to disorders such as mood and anxiety). • The patients themselves are not aware of the underlying neurological causes • According to Mowrer’s two factor theory we propose that initial contact with a substance happens by chance and they ascribe “feeling better” to the substance Footer

34. Subsequent use and “positive effects” are positively reinforced (operant conditioning) • Sensation seeking and resultant risk taking behaviour is a predisposing risk factor • We postulate that sensation seeking shares the same neurological and substrates with ADHD which is why we assume that it predisposes adults with ADHD to substance abuse Footer

35. Future research Footer

36. So what do we propose to do? Footer

37. Conclusion • It seems unlikely to me that we will continue to punish people for misconduct when the crossed wires that spark their behaviour become as clear to see as a broken bone. Rather, I hope (and expect) we will use our knowledge of the brain to develop treatments for sick brains that will be infinitely more effective than the long-winded, hit and miss psychological therapies we use today. (Carter, 1998, p.334) Footer