Objectives. Cortical thickness over time. Cortical thickness over time. ADHD neurobiology

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1 The Neuroscience of Attention Deficit Hyperactivity Disorder: Implications for Treatment Steven R., M.D. Professor and Chief Division of Child and Adolescent Psychiatry UTHSCSA Source Purdue Disclosures of Potential Conflicts In-kind Books, Stock or Research Advisor/ Expert Speakers Services Intellectual Equity > Funding Consultant Witness Bureau (example: Property $, travel) X Shire X X Honorarium or expenses for this presentation or meeting Objectives Describe the neuroanatomy and neurophysiology of the developing brain in children and adolescents Describe the differences in the neuroanatomy and neurophysiology associated with Attention Deficit Hyperactivity Disorder (ADHD) Discuss the impact that the current knowledge of neurobiology in children and adolescents has on current treatment strategies in ADHD Multifaceted Neurology of ADHD Neuroanatomy Attention Networks Cerebellar networks Reward processes Default network Connectivity Cortical thickness over time Cortical thickness over time BIOL PSYCHIATRY 3;74:599 66

2 Cortical Surface Area Attaining peak surface area BIOL PSYCHIATRY ;7:9 97 How do stimulants effect brain growth? Shaw et al. Am J Psychiatry 9; 66: patients with ADHD, mean age yrs, 4 taking stimulants at basline 9 patients stopped taking medication (reasons not specified) 9 off stimulants compared to 4 on stimulants at age 6 Small numbers in each group exposed to alpha agonists and antidepressants Meta-analysis of fmri data Corbetta & Shulman ()

3 Meta-analysis of fmri data Meta-analysis of stimulant effects (single dose) Rubia et al, Biological Psychiatry Cerebellum in ADHD Reward Processes in ADHD Mulder, Durston et al., JAACAP Jan 8 Ventral Tegmental/Nucleus Accumbens Ventral striatum and Reward 3

4 Ventral striatum and Reward Default Mode Network Active mode Anterior Cingulate rifg, rmfg Brains in the resting state Default mode Precuneus Posterior Cingulate VM PFC Castellanos et al. Biol Psychiatry 63: 33, 8 Differences in Resting State MPH and the default mode network (DMN) Liddle et al. J Child Psychol Psychaitry, 5: 76-77, 4 children with ADHD (age 9-5 years), 4 age matched controls. FMRI with Go/No Go task ADHD children scanned on and off medication All subjects did low and high reward. 4

5 MPH and the default mode network Functional Connectivity Cool (blue) colors represent deactivation the DMN Tomasi & Volkow, Biol Psychiatry 7:44, 47 ADHD 34 Controls Functional scans Metaanalysis More connected to limbic, less to DMN Functional Connectivity Emotional Processing in ADHD Posner et al. JAACAP 5:88, Subliminal fearful faces presented during FMRI Age and IQ matched control and adolescent with ADHD Tomasi & Volkow, Biol Psychiatry 7:44, Emotional Processing in ADHD Connectivity between PFC and amygdala on y axis Posner et al. JAACAP 5:88, Arnsten & Rubia, JAACAP;5(4):

6 Are these deficits unique to ADHD? Other issues During an impulse control task (in bipolar subjects without ADHD): Bipolar children have less ACC activation than controls Bipolar adults have more ACC activation than controls Am J Psychiatry. ;69(6): Genome Wide Association Studies (GWAS) have not: Confirmed genes found in earlier candidate gene studies Found genes of major effect in spite of high heritability (~.7-.8) CNVs more numerous in ADHD with developmental disabilities Possible that early experience shapes brain development (epigenetics) Implications for Clinicians No single neurological lesion that defines ADHD. Neurological dysfunction detected by current technology (EEG, etc) would be found in any disorder that impairs attention/impulse control. How do tell ADHD from? Not really a relevant question. Using a chronic treatment model Reduce symptoms with stimulant medication- not a bad thing- no need to be constantly looking for alternatives Brain differences vs. brain damage Asthma as a model Effort is to ADHD as exercise is to asthma Good and bad stigma Behavior management The Psychology of ADHD There is no Why? Everything is short term Parental ADHD/ADHD traits a problem ADHD children do not process rewards and punishments similar to typically developing children: Always go for immediate reward Cannot delay gratification Social rewards not salient - i.e. reinforcing Don t hit sister Do things st time asked Behavioral Approaches Mon Tues Wen Thu Fri Sat Sun Homework Total 6

7 Behavioral Approaches Behavioral approaches are mostly adjunctive Time consuming Differences in outcome IQ Family Lack of aggressive comorbidity 7

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