517949 research-article2014
APY0010.1177/1039856213517949Australasian PsychiatryPoulton and Nanan
AP
Attention-deficit hyperactivity disorder
The attention deficit hyperactivity disorder phenotype as a summation of deficits in executive functioning and reward sensitivity: does this explain its relationship with oppositional defiant disorder?
Australasian Psychiatry 2014, Vol 22(2) 174–178 © The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1039856213517949 apy.sagepub.com
Alison Poulton Sydney Medical School Nepean, University of Sydney, Penrith, NSW, Australia Ralph Nanan Sydney Medical School Nepean, University of Sydney, Penrith, NSW, Australia
Abstract Objective: Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) commonly coexist but the relationship between them has not been well explained. We present a view of the ADHD phenotype as a summation of deficits in executive functioning and reward sensitivity and apply this to explain its co-occurrence with ODD. Model: ADHD relates to difficulty in sustaining concentration for completing tasks. This is associated with lack of reward due to lack of achievement. The unfavorable balance of effort to reward in ADHD is exacerbated in ODD, a condition in which lack of reward is responsible for an adverse effect on mood resulting in a negative attitude and oppositional behavior. We have called this model the “Mental effort-reward imbalances model”. Conclusion: This model predicts that oppositional symptoms would be highly prevalent in ADHD, to the extent that ODD would be a frequent co-morbidity. Keywords: attention deficit hyperactivity disorder, oppositional defiant disorder, stimulant medication
O
ppositional defiant disorder (ODD) usually occurs in association with attention deficit hyperactivity disorder (ADHD) but is considered to be separate diagnoses by DSM-IV,1 DSM-52 and ICD-10.3 If they are separate disorders, their relationship and co-occurrence requires some explanation. In this paper we aim to present our clinical hypothesis of the ADHD phenotype as a summation of the deficits in the core features of ADHD amplified and exacerbated by inadequate experience of reward leading to the temperamental features of ODD.
motivation, regulation of attention and cognitive control of behavior.4 The core feature of inattention leading to difficulty in completing tasks requiring sustained concentration has been described as mental fatigue.5 At an individual level this may be moderated by ability, so that an able child can complete a task more quickly and with less mental effort than his or her peers, masking the effects of mild ADHD. Motivation to put more effort into concentrating can be increased by adding incentives of positive reward or the avoidance of punishment.6 Reward and punishment may not be external; they may include the intrinsic satisfaction that an
Background The clinical diagnoses of ADHD and ODD are based on behavioral phenotypes. ADHD is characterized by a short attention span (inattention), hyperactivity and impulsivity.1 These features are related to the executive functioning of the prefrontal cortex which is critical for
Corresponding author: Alison Poulton, Department of Paediatrics, Nepean Hospital, University of Sydney, PO Box 63, Penrith, NSW 2751 Australia. Email: [email protected]
174 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Poulton and Nanan
Figure 1. Model of ADHD and ODD based on imbalances in the effort and reward for achievement. individual experiences on task completion, or conversely the dissatisfaction of failure. Individuals with ODD are typically uncooperative, angry and defiant and may deliberately annoy.1 It has been suggested that ODD and the related diagnosis conduct disorder (CD) are associated with hyposensitivity to reward.7 This may result in antisocial behavior resulting from a need for excitement to counteract a state of boredom and stimulus deprivation.8 Antisocial or aggressive behavior can be rewarding, being associated with substantial limbic dopamine (DA) release in the nucleus accumbens.9 Whether the DA itself is responsible for the experience of reward or whether it simply increases the anticipated value of the reward (reward salience) has been a matter of debate.10 However, increased reward salience would have the effect of increasing the motivation for reward-seeking behavior which in turn would result in a more rewarding existence due to higher levels of achievement. It is logical to consider whether the negative and disagreeable affect typical of individuals with ODD might be attributable to a relative lack of DA activity resulting in less reward and compensated for in CD with rule-breaking and antisocial behavior. Deficits in reward processing would have the potential to exacerbate the symptoms of ADHD because tasks are perceived as less rewarding and therefore less worthwhile for putting in the effort.
Mental effort-reward imbalances model According to this model (Figure 1) the individual puts in effort, achieves and is rewarded. The reward promotes more effort, reducing the perceived cost of the task. Individuals who experience ample reward would tend to have a good mood and a co-operative outlook. This model views the ADHD phenotype as a condition in which there is an unfavorable balance between mental effort and reward, such that the reward experienced is not worth the effort. This leads to lower levels of achievement, as manifested by tasks left unfinished. The
primary mechanism causing the imbalance in ‘pure’ ADHD relates to the core executive functioning deficits which necessitate a greater cognitive effort in order to gain the rewards associated with cognitive achievement. ODD provides a secondary mechanism, with a generalized reduction in reward that reduces the level of motivation, exacerbating the particular difficulty in overcoming executive functioning deficits in ADHD and lowering the mood. Because these two mechanisms are additive in their effects, most individuals with the ADHD phenotype are likely to have both of these mechanisms operating to varying degrees. The expected clinical picture in relation to deficits in executive functioning and experience of reward is summarized in Table 1. This model predicts that an individual who has a minor degree of ADHD is far more likely to exceed the diagnostic threshold for this condition if he or she also has ODD related deficits in reward sensitivity. Therefore in children with the ADHD phenotype we propose that the level of severity, as measured by the level of achievement, will be proportionate to a summation of the mental deficits for executive functioning plus those for reward sensitivity. It would follow that features of ODD would be highly prevalent in cohorts of individuals with ADHD. Those individuals most severely impaired will meet diagnostic thresholds for both conditions.
Discussion Our framework presented here has similarities to the dual pathway model of Sonuga-Barke. He proposed that the ADHD phenotype could be the end result of either of two distinct mechanisms.11 The first of these is executive functioning deficits, and the second relates to altered reward processes affecting motivation and associated with delay aversion. However, rather than deficits in executive functioning and reward processing being alternative routes to the same clinical phenotype, we have postulated that the particular clinical picture varies depending on the balance of the extent to which each of
175 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Australasian Psychiatry 22(2)
Table 1. Clinical picture in relation to the balance of deficit in executive functioning and ability to experience reward Deficits in executive Deficits in Clinical picture functioning experience of reward ‘Pure’ ADHD – subthreshold or mild
+
‘Pure’ ADHD – ++ substantial ‘Pure’ ODD – subthreshold or mild ‘Pure’ ODD – substantial
+
‘Typical’ ADHD
+
+
Combination of ADHD and ODD
++
++
++
Cognitive tasks are an effort but this can be overcome, particularly if the child is intellectually able; child is generally cooperative. Cognitive tasks are a substantial effort; child is generally co-operative. Can be moody and negative in attitude; responsive to positive reinforcement. Moody, negative in attitude and reward seeking; may be highly competitive. Cognitive tasks are an effort; negative behavior is particularly directed towards tasks requiring mental effort. Generally negative, particularly towards cognitive tasks but even non-cognitive tasks (e.g. self-help) may be too much effort; seeking high reward for minimal mental effort.
ADHD: attention deficit hyperactivity disorder; ODD: oppositional defiant disorder.
these pathways is affected. We suggest that the executive functioning deficits relate principally to the core features of ADHD, with more inattention and disorganization, while deficits in reward processing have an adverse effect on mood and attitude, resulting in more oppositional symptoms. For any individual, the symptomatology will depend not only on the severity of deficits in each pathway but also on their relative balance. If symptoms of ADHD represent a summation of deficits in two distinct modalities, it would follow that individuals of comparable clinical severity would not necessarily have both pathways affected to the same extent. For example, individuals with more significant deficits in reward processing might meet diagnostic criteria for ADHD with relatively less severe deficits in executive functioning. This could explain the unexpected results obtained by Swanson et al.12 They subdivided children with ADHD combined type into those with and without a 7-repeat allele of the DA receptor D4 gene (DRD4 7-repeat allele) and compared them on tasks of executive functioning. Children with the DRD4 7-repeat allele may be sub-sensitive to endogenous DA,13 and Swanson et al. predicted that this would correlate with ADHD severity and therefore this subgroup of children with ADHD would perform worse. In fact they not only performed better, but they did as well as control children without ADHD. Swanson et al. also observed higher ratings for ODD in these children, although this was not
statistically significant as there were only 13 and 19 individuals per group. We suggest that the DRD4 7-repeat allele may lead to deficits in reward sensitivity and would therefore correlate with higher symptom scores for ODD, and could even be a marker for this condition. It would follow that individuals with DRD4 7-repeat allele would meet clinical diagnostic thresholds for ADHD with a lower level of impairment in executive functioning. This could explain the findings of Swanson et al. It is interesting to note that symptoms of both ADHD and ODD may improve with the stimulant medications dexamphetamine (DEX) and methylphenidate (MPH).14–18 These stimulants interact with amine transporter systems, decreasing the synaptic reuptake of DA and noradrenaline.19 DEX also induces the release of newly synthesized DA,20 and has greater potency than MPH for inhibiting the reuptake of serotonin.21 When used therapeutically, both medications are also associated with weight loss.22 In 1977 Sprague and Sleator showed that MPH at a lower dose of 0.3 mg/kg led to more improvement in learning but on a higher dose of 1 mg/kg there was a decrement in learning while social behavior improved.23 This hints at two separate stimulant effects, each with its own therapeutic window. At lower doses the improvement in learning might be principally due to enhancement in executive functioning,24 with corresponding improvement in features of inattention and
176 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Poulton and Nanan
impulsivity. At higher doses the improvement in social behavior could be due to an enhancement in DA leading to amelioration of the state of reward deficit. A rise in striatal DA in response to MPH has been observed in individuals carrying out a boring task,25 and this was associated with a perception of greater interest for the task, which would have increased their level of motivation. In children with ODD, if mundane tasks are perceived as more rewarding they might be accomplished with less reluctance, with successful task completion being associated with an improvement in mood and attitude. These effects would lead to behavior appearing more compliant and less oppositional. There is evidence that at low doses stimulant medications and atomoxetine selectively increase levels of DA and noradrenaline in the prefrontal cortex and that this is associated with improvements in cognitive functioning, with an inverted U-shaped dose-response curve. At stimulant doses greater than those associated with cognitive enhancement there is more generalized DA elevation involving other areas of the brain.26 These dose-dependent regional increases in neurotransmitter concentrations might correspond to improvements in executive functioning and reward processing, respectively. We suggest that by potentiating limbic DA, the stimulant at higher doses may counteract the state of reward deficit, leading to a corresponding improvement in mood and behavior. Titration for optimal behavioral functioning may not simultaneously optimize executive functioning, as these may involve separate mechanisms and require different drug concentrations.
Stimulant medication is recognized to improve cognitive functioning in normal individuals unaffected by ADHD.27 However, we would anticipate that as the balance of ODD to ‘pure’ ADHD increases, the stimulant associated improvement in cognition would be less marked and the assessment of maximal clinical improvement would occur at relatively higher doses and be associated with a more generalized increase in DA levels, correlating with improvement in mood and behavior. Clarification of the clinical effects of low and high-dose stimulant medication may lead to more informed prescribing. For example, it is important to understand that although higher concentrations of stimulant medications may be required to treat ODD, this could compromise obtaining optimal improvement in executive functioning. Disclosure The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.
References 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders IV. Washington, DC: APA, 1994. 2. American Psychiatric Association. DSMTF. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Arlington, VA: American Psychiatric Association, 2013. 3. World Health Organization. The International Classification of Diseases. Geneva: World Health Organization, 1992. 4. Arnsten AF and Rubia K. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. J Am Acad Child Adolesc Psychiatry 2012; 51(4): 356–367. 5. Parr VE. Auditory word discrimination in male children diagnosed as having minimal brain dysfunction. J Clin Psychol 1977; 33(4): 1064–1069.
Conclusions We have provided a plausible explanation for the association between ADHD and ODD. If future research is supportive, our conceptualization may provide some important insight into the mechanisms underlying behavior perceived as socially dysfunctional. For example it would be valuable for affected individuals and their families to understand the mood and attitude symptomatic of a state of reward deficit and the sometimes extreme strategies that individuals may use to obtain reward. These may include thrill seeking, overeating, promiscuity, antisocial behavior and possibly also outbursts of emotion. Our model is based principally on our observations based on our years of clinical experience. However, it is important to validate the theoretical model with neuroscientific studies. This could be done by using different doses of stimulant medication and taking advantage of the apparently distinct pharmacological effects on cognitive functioning and behavior.23 Using positron emission tomography, the regional changes in DA activity with a range of doses could be correlated with tests of cognitive functioning and with the changes in symptom severity for the core features of ADHD and those of ODD.
6. Groom MJ, Liddle EB, Scerif G, et al. Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder. J Child Psychol Psychiatry 2013; 54: 836–845. 7. Matthys W, Vanderschuren LJ and Schutter DJ. The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains. Dev Psychopathol 2013; 25(1): 193–207. 8. Quay HC. Psychopathic personality as pathological stimulation-seeking. Am J Psychiatry 1965; 122: 180–183. 9. Buckholtz JW, Treadway MT, Cowan RL, et al. Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci 2010; 13(4): 419–421. 10. Berridge KC. From prediction error to incentive salience: mesolimbic computation of reward motivation. Eur J Neurosci 2012; 35(7): 1124–1143. 11. Sonuga-Barke EJ. The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev 2003; 27(7): 593–604. 12. Swanson J, Oosterlaan J, Murias M, et al. Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proc Natl Acad Sci U S A 2000; 97(9): 4754–4759. 13. Jovanovic V, Guan HC and Van Tol HH. Comparative pharmacological and functional analysis of the human dopamine D4.2 and D4.10 receptor variants. Pharmacogenetics 1999; 9(5): 561–568. 14. Brown TE and Landgraf JM. Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgrad Med 2010; 122(5): 42–51.
177 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Australasian Psychiatry 22(2) 15. Guimaraes AP, Zeni C, Polanczyk G, et al. MAOA is associated with methylphenidate improvement of oppositional symptoms in boys with attention deficit hyperactivity disorder. Int J Neuropsychopharmacol 2009; 12(5): 709–714. 16. Hale JB, Reddy LA, Semrud-Clikeman M, et al. Executive impairment determines ADHD medication response: implications for academic achievement. J Learn Disabil 2011; 44(2): 196–212. 17. MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 1999; 56(12): 1073–1086. 18. Sinzig J, Dopfner M, Lehmkuhl G, et al. Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2007; 17(4): 421–432. 19. Madras BK, Miller GM and Fischman AJ. The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry 2005; 57(11): 1397–1409.
22. Greenhill LL, Halperin JM and Abikoff H. Stimulant medications. J Am Acad Child Adolesc Psychiatry 1999; 38(5): 503–512. 23. Sprague RL and Sleator EK. Methylphenidate in hyperkinetic children: differences in dose effects on learning and social behavior. Science 1977; 198(4323): 1274–1276. 24. Arnsten AF and Dudley AG. Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder. Behav Brain Funct 2005; 1(1): 2. 25. Volkow ND, Wang GJ, Fowler JS, et al. Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain. Am J Psychiatry 2004; 161(7): 1173–1180.
20. Chiueh CC and Moore KE. D-amphetamine-induced release of “newly synthesized” and “stored” dopamine from the caudate nucleus in vivo. J Pharmacol Exp Ther 1975; 192(3): 642–653.
26. Berridge CW and Devilbiss DM. Psychostimulants as cognitive enhancers: the prefrontal cortex, catecholamines, and attention-deficit/hyperactivity disorder. Biol Psychiatry 2011; 69(12): e101–e111.
21. Kuczenski R and Segal DS. Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 1997; 68(5): 2032–2037.
27. Vaidya CJ, Austin G, Kirkorian G, et al. Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proc Natl Acad Sci U S A 1998; 95(24): 14494–14499.
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APY0010.1177/1039856213517949Australasian PsychiatryPoulton and Nanan
AP
Attention-deficit hyperactivity disorder
The attention deficit hyperactivity disorder phenotype as a summation of deficits in executive functioning and reward sensitivity: does this explain its relationship with oppositional defiant disorder?
Australasian Psychiatry 2014, Vol 22(2) 174–178 © The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1039856213517949 apy.sagepub.com
Alison Poulton Sydney Medical School Nepean, University of Sydney, Penrith, NSW, Australia Ralph Nanan Sydney Medical School Nepean, University of Sydney, Penrith, NSW, Australia
Abstract Objective: Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) commonly coexist but the relationship between them has not been well explained. We present a view of the ADHD phenotype as a summation of deficits in executive functioning and reward sensitivity and apply this to explain its co-occurrence with ODD. Model: ADHD relates to difficulty in sustaining concentration for completing tasks. This is associated with lack of reward due to lack of achievement. The unfavorable balance of effort to reward in ADHD is exacerbated in ODD, a condition in which lack of reward is responsible for an adverse effect on mood resulting in a negative attitude and oppositional behavior. We have called this model the “Mental effort-reward imbalances model”. Conclusion: This model predicts that oppositional symptoms would be highly prevalent in ADHD, to the extent that ODD would be a frequent co-morbidity. Keywords: attention deficit hyperactivity disorder, oppositional defiant disorder, stimulant medication
O
ppositional defiant disorder (ODD) usually occurs in association with attention deficit hyperactivity disorder (ADHD) but is considered to be separate diagnoses by DSM-IV,1 DSM-52 and ICD-10.3 If they are separate disorders, their relationship and co-occurrence requires some explanation. In this paper we aim to present our clinical hypothesis of the ADHD phenotype as a summation of the deficits in the core features of ADHD amplified and exacerbated by inadequate experience of reward leading to the temperamental features of ODD.
motivation, regulation of attention and cognitive control of behavior.4 The core feature of inattention leading to difficulty in completing tasks requiring sustained concentration has been described as mental fatigue.5 At an individual level this may be moderated by ability, so that an able child can complete a task more quickly and with less mental effort than his or her peers, masking the effects of mild ADHD. Motivation to put more effort into concentrating can be increased by adding incentives of positive reward or the avoidance of punishment.6 Reward and punishment may not be external; they may include the intrinsic satisfaction that an
Background The clinical diagnoses of ADHD and ODD are based on behavioral phenotypes. ADHD is characterized by a short attention span (inattention), hyperactivity and impulsivity.1 These features are related to the executive functioning of the prefrontal cortex which is critical for
Corresponding author: Alison Poulton, Department of Paediatrics, Nepean Hospital, University of Sydney, PO Box 63, Penrith, NSW 2751 Australia. Email: [email protected]
174 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Poulton and Nanan
Figure 1. Model of ADHD and ODD based on imbalances in the effort and reward for achievement. individual experiences on task completion, or conversely the dissatisfaction of failure. Individuals with ODD are typically uncooperative, angry and defiant and may deliberately annoy.1 It has been suggested that ODD and the related diagnosis conduct disorder (CD) are associated with hyposensitivity to reward.7 This may result in antisocial behavior resulting from a need for excitement to counteract a state of boredom and stimulus deprivation.8 Antisocial or aggressive behavior can be rewarding, being associated with substantial limbic dopamine (DA) release in the nucleus accumbens.9 Whether the DA itself is responsible for the experience of reward or whether it simply increases the anticipated value of the reward (reward salience) has been a matter of debate.10 However, increased reward salience would have the effect of increasing the motivation for reward-seeking behavior which in turn would result in a more rewarding existence due to higher levels of achievement. It is logical to consider whether the negative and disagreeable affect typical of individuals with ODD might be attributable to a relative lack of DA activity resulting in less reward and compensated for in CD with rule-breaking and antisocial behavior. Deficits in reward processing would have the potential to exacerbate the symptoms of ADHD because tasks are perceived as less rewarding and therefore less worthwhile for putting in the effort.
Mental effort-reward imbalances model According to this model (Figure 1) the individual puts in effort, achieves and is rewarded. The reward promotes more effort, reducing the perceived cost of the task. Individuals who experience ample reward would tend to have a good mood and a co-operative outlook. This model views the ADHD phenotype as a condition in which there is an unfavorable balance between mental effort and reward, such that the reward experienced is not worth the effort. This leads to lower levels of achievement, as manifested by tasks left unfinished. The
primary mechanism causing the imbalance in ‘pure’ ADHD relates to the core executive functioning deficits which necessitate a greater cognitive effort in order to gain the rewards associated with cognitive achievement. ODD provides a secondary mechanism, with a generalized reduction in reward that reduces the level of motivation, exacerbating the particular difficulty in overcoming executive functioning deficits in ADHD and lowering the mood. Because these two mechanisms are additive in their effects, most individuals with the ADHD phenotype are likely to have both of these mechanisms operating to varying degrees. The expected clinical picture in relation to deficits in executive functioning and experience of reward is summarized in Table 1. This model predicts that an individual who has a minor degree of ADHD is far more likely to exceed the diagnostic threshold for this condition if he or she also has ODD related deficits in reward sensitivity. Therefore in children with the ADHD phenotype we propose that the level of severity, as measured by the level of achievement, will be proportionate to a summation of the mental deficits for executive functioning plus those for reward sensitivity. It would follow that features of ODD would be highly prevalent in cohorts of individuals with ADHD. Those individuals most severely impaired will meet diagnostic thresholds for both conditions.
Discussion Our framework presented here has similarities to the dual pathway model of Sonuga-Barke. He proposed that the ADHD phenotype could be the end result of either of two distinct mechanisms.11 The first of these is executive functioning deficits, and the second relates to altered reward processes affecting motivation and associated with delay aversion. However, rather than deficits in executive functioning and reward processing being alternative routes to the same clinical phenotype, we have postulated that the particular clinical picture varies depending on the balance of the extent to which each of
175 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Australasian Psychiatry 22(2)
Table 1. Clinical picture in relation to the balance of deficit in executive functioning and ability to experience reward Deficits in executive Deficits in Clinical picture functioning experience of reward ‘Pure’ ADHD – subthreshold or mild
+
‘Pure’ ADHD – ++ substantial ‘Pure’ ODD – subthreshold or mild ‘Pure’ ODD – substantial
+
‘Typical’ ADHD
+
+
Combination of ADHD and ODD
++
++
++
Cognitive tasks are an effort but this can be overcome, particularly if the child is intellectually able; child is generally cooperative. Cognitive tasks are a substantial effort; child is generally co-operative. Can be moody and negative in attitude; responsive to positive reinforcement. Moody, negative in attitude and reward seeking; may be highly competitive. Cognitive tasks are an effort; negative behavior is particularly directed towards tasks requiring mental effort. Generally negative, particularly towards cognitive tasks but even non-cognitive tasks (e.g. self-help) may be too much effort; seeking high reward for minimal mental effort.
ADHD: attention deficit hyperactivity disorder; ODD: oppositional defiant disorder.
these pathways is affected. We suggest that the executive functioning deficits relate principally to the core features of ADHD, with more inattention and disorganization, while deficits in reward processing have an adverse effect on mood and attitude, resulting in more oppositional symptoms. For any individual, the symptomatology will depend not only on the severity of deficits in each pathway but also on their relative balance. If symptoms of ADHD represent a summation of deficits in two distinct modalities, it would follow that individuals of comparable clinical severity would not necessarily have both pathways affected to the same extent. For example, individuals with more significant deficits in reward processing might meet diagnostic criteria for ADHD with relatively less severe deficits in executive functioning. This could explain the unexpected results obtained by Swanson et al.12 They subdivided children with ADHD combined type into those with and without a 7-repeat allele of the DA receptor D4 gene (DRD4 7-repeat allele) and compared them on tasks of executive functioning. Children with the DRD4 7-repeat allele may be sub-sensitive to endogenous DA,13 and Swanson et al. predicted that this would correlate with ADHD severity and therefore this subgroup of children with ADHD would perform worse. In fact they not only performed better, but they did as well as control children without ADHD. Swanson et al. also observed higher ratings for ODD in these children, although this was not
statistically significant as there were only 13 and 19 individuals per group. We suggest that the DRD4 7-repeat allele may lead to deficits in reward sensitivity and would therefore correlate with higher symptom scores for ODD, and could even be a marker for this condition. It would follow that individuals with DRD4 7-repeat allele would meet clinical diagnostic thresholds for ADHD with a lower level of impairment in executive functioning. This could explain the findings of Swanson et al. It is interesting to note that symptoms of both ADHD and ODD may improve with the stimulant medications dexamphetamine (DEX) and methylphenidate (MPH).14–18 These stimulants interact with amine transporter systems, decreasing the synaptic reuptake of DA and noradrenaline.19 DEX also induces the release of newly synthesized DA,20 and has greater potency than MPH for inhibiting the reuptake of serotonin.21 When used therapeutically, both medications are also associated with weight loss.22 In 1977 Sprague and Sleator showed that MPH at a lower dose of 0.3 mg/kg led to more improvement in learning but on a higher dose of 1 mg/kg there was a decrement in learning while social behavior improved.23 This hints at two separate stimulant effects, each with its own therapeutic window. At lower doses the improvement in learning might be principally due to enhancement in executive functioning,24 with corresponding improvement in features of inattention and
176 Downloaded from apy.sagepub.com at GEORGIAN COURT UNIV on March 11, 2015
Poulton and Nanan
impulsivity. At higher doses the improvement in social behavior could be due to an enhancement in DA leading to amelioration of the state of reward deficit. A rise in striatal DA in response to MPH has been observed in individuals carrying out a boring task,25 and this was associated with a perception of greater interest for the task, which would have increased their level of motivation. In children with ODD, if mundane tasks are perceived as more rewarding they might be accomplished with less reluctance, with successful task completion being associated with an improvement in mood and attitude. These effects would lead to behavior appearing more compliant and less oppositional. There is evidence that at low doses stimulant medications and atomoxetine selectively increase levels of DA and noradrenaline in the prefrontal cortex and that this is associated with improvements in cognitive functioning, with an inverted U-shaped dose-response curve. At stimulant doses greater than those associated with cognitive enhancement there is more generalized DA elevation involving other areas of the brain.26 These dose-dependent regional increases in neurotransmitter concentrations might correspond to improvements in executive functioning and reward processing, respectively. We suggest that by potentiating limbic DA, the stimulant at higher doses may counteract the state of reward deficit, leading to a corresponding improvement in mood and behavior. Titration for optimal behavioral functioning may not simultaneously optimize executive functioning, as these may involve separate mechanisms and require different drug concentrations.
Stimulant medication is recognized to improve cognitive functioning in normal individuals unaffected by ADHD.27 However, we would anticipate that as the balance of ODD to ‘pure’ ADHD increases, the stimulant associated improvement in cognition would be less marked and the assessment of maximal clinical improvement would occur at relatively higher doses and be associated with a more generalized increase in DA levels, correlating with improvement in mood and behavior. Clarification of the clinical effects of low and high-dose stimulant medication may lead to more informed prescribing. For example, it is important to understand that although higher concentrations of stimulant medications may be required to treat ODD, this could compromise obtaining optimal improvement in executive functioning. Disclosure The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.
References 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders IV. Washington, DC: APA, 1994. 2. American Psychiatric Association. DSMTF. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Arlington, VA: American Psychiatric Association, 2013. 3. World Health Organization. The International Classification of Diseases. Geneva: World Health Organization, 1992. 4. Arnsten AF and Rubia K. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. J Am Acad Child Adolesc Psychiatry 2012; 51(4): 356–367. 5. Parr VE. Auditory word discrimination in male children diagnosed as having minimal brain dysfunction. J Clin Psychol 1977; 33(4): 1064–1069.
Conclusions We have provided a plausible explanation for the association between ADHD and ODD. If future research is supportive, our conceptualization may provide some important insight into the mechanisms underlying behavior perceived as socially dysfunctional. For example it would be valuable for affected individuals and their families to understand the mood and attitude symptomatic of a state of reward deficit and the sometimes extreme strategies that individuals may use to obtain reward. These may include thrill seeking, overeating, promiscuity, antisocial behavior and possibly also outbursts of emotion. Our model is based principally on our observations based on our years of clinical experience. However, it is important to validate the theoretical model with neuroscientific studies. This could be done by using different doses of stimulant medication and taking advantage of the apparently distinct pharmacological effects on cognitive functioning and behavior.23 Using positron emission tomography, the regional changes in DA activity with a range of doses could be correlated with tests of cognitive functioning and with the changes in symptom severity for the core features of ADHD and those of ODD.
6. Groom MJ, Liddle EB, Scerif G, et al. Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder. J Child Psychol Psychiatry 2013; 54: 836–845. 7. Matthys W, Vanderschuren LJ and Schutter DJ. The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains. Dev Psychopathol 2013; 25(1): 193–207. 8. Quay HC. Psychopathic personality as pathological stimulation-seeking. Am J Psychiatry 1965; 122: 180–183. 9. Buckholtz JW, Treadway MT, Cowan RL, et al. Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci 2010; 13(4): 419–421. 10. Berridge KC. From prediction error to incentive salience: mesolimbic computation of reward motivation. Eur J Neurosci 2012; 35(7): 1124–1143. 11. Sonuga-Barke EJ. The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev 2003; 27(7): 593–604. 12. Swanson J, Oosterlaan J, Murias M, et al. Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proc Natl Acad Sci U S A 2000; 97(9): 4754–4759. 13. Jovanovic V, Guan HC and Van Tol HH. Comparative pharmacological and functional analysis of the human dopamine D4.2 and D4.10 receptor variants. Pharmacogenetics 1999; 9(5): 561–568. 14. Brown TE and Landgraf JM. Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgrad Med 2010; 122(5): 42–51.
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