ADHD - FACT OR FICTION A NEUROPSYCHIATRIC VIEW

Transcription

1 ADHD - FACT OR FICTION A NEUROPSYCHIATRIC VIEW

2 ADHD - FACT OR FICTION GOALS A NEUROPSYCHIATRIC VIEW 1. Review Brain Structure and Function relevant to ADHD behavior 2. Understand and apply the concept of Response Inhibition as it applies to the ADHD syndrome 3. Understand the rationale for stimulant therapy; i.e. Neurotransmitter Pharmaco-modification. 4. Review Co-morbid Conditions and Syndrome Imposters 5. Review a Bio-psycho-social model treatment of ADHD

3 I. Brain Structure Relevant to ADHD Behavior ` A. Frontal Subcortical Circuits or Loops 1.) Frontal Lobes; Dorsal, Medial, and Orbital Pre- Frontal Cortexes 2.) Basal Ganglia; Caudate-Putamen, Globus Pallidus 3.) Substantia Nigra, Subthalamic Nucleus 4.) Thalamus B. Connections with the Limbic System 1.) Amygdala and medial Temporal Lobe 2.) Cingulate, anterior and posterior regions 3.) Nucleus Accumbens

4 C. Alexander s LOOPS 1. Skeletomotor Loop 2 Oculomotor Loop 3. Dorsolateral Pre-frontal Cortex Loop 4. Lateral Orbital Frontal Loop 5. Medial Orbital Frontal Loop 6. Anterior Cingulate Loop 7. InferoTemporal Loop Reference: Frontal Subcortical Circuits in Psychiatric and Neurological Disorders; D. Lichter, J. J. Cummings, Pp.44-58; Guilford Press 4

5 D. Neural Networks- 1. Work of Pandya, Mesulum 2. Integrative Aspects of Basal Ganglia Circuitry - pages 72,73 ; The Basal Ganglia IV; Edited by G. Percheron, Plenum Press, NY, 1994

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7 E. Neurotransmitters Receptors: 1. Dopamine 2. Serotonin 3. Norepinephrine 4. GABA 5. Enkephalin 6. Glutamate

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9 Neuron Message Delivery System Illustration by Lydia Kibiuk copyright 1996 by Lydia Kibiuk

10 Normal Aging

11 II. Imaging Techniques A. Gross anatomy dissections B. MRI Magnetic Resonance Imaging C. SPECT Single Photon Emission Computed Tomography D. PET Positron Emission Tomography

12 III. Normal Brain function Relevant to ADHD A. Memory 1.) Memory in the Cerebral Cortex; J. Fuster, 1995, MIT Press; pages a.) Delayed Match to Sample- Delayed Response; Cortical Memory Cells and the Sulcus Principalis- P. 242, 245 b.) Images pages 242, 245 Prefrontal Cortex; Fuster

13 B. Attention 1. This is a property system. 2. Alertness- role of recognizing the motivational significance or an external stimulus. 3. Vigilance; sustained attention and inhibition of competing stimuli. 4. Shifting attention; role of monitoring Extra Personal versus Intra Personal Space 13 13

14 C. Executive Function 1.) Central a.) Refers to a conceptual approach towards integrating functions attributed to higher level thinking; b.) Cluster of processes that include: Evaluation, Organization, Formulation of Planning Strategies for Problem Solving, Regulation and Flexibility of Such Processes of Goal Directed Behavior. c.) An Online phenomenon of ongoing monitoring of IF NOW THIS, THEN LATER THAT. d.) Monitoring of Present state working memory (perhaps in parallel) with ongoing monitoring of Past and Future reconciling. CROSS TEMPORAL ORGANIZATION!!!!

15 D. Executive Function 1. A CROSS TEMPORAL ORGANIZATION OF EMOTIONAL-AFFECTIVE STATES 2. The attribution of emotional valence to ongoing working memory; EMOTIONAL REGULATION. 3. A self monitoring process of emotionality

16 Examples of Normal Developmental Executive Emotional Regulation 1. Age 6- children resist distraction 2. Age 10 full competancy in hypothesis testing, organized search, Impulse control 3. Age 12- adult level of motor sequencing, verbal fluency, planning skills 4. Event related motor potentials show an increase in processing speed: relates to Synaptogenesis Testing includes: Tower of London, Tower of Hanoi, Stroop, Wisconsin Card Sorting Test, Visual Search, Verbal Fluency, Motor Planning, Matching Figures Test. Page 160

17 Wisconsin Card Sorting Test Tower of London Test

18 III Rationale for Stimulant Therapy: Neurotransmitter Pharmacomodification 1. Neurotransmitter synthesis and release 2. Neuroreceptor pharmacology and effect of blocking receptor, blocking transporter proteins, inhibition of reuptake, increase in vesicle release. 3. Neurotransmittersa.) Dopamine; synthesis in Substantia Nigra of midbrain; tracts to Frontal lobes, Basal ganglia, hypothalamus. 4 functions of relevance; vasomotor tone, Motivation and Reward, Working Memory and Attention, Motor control b.) Serotonin; synthesis in the Dorsal Raphe of the brainstem;function in affective regulation

19 Neurotransmitters Continued c.) Norepinephrine; synthesis in the Locus Ceruleus of brainstem; function in Attention systems and vasomotor tone d.) GABA- (G- Aminobutyric acid) inhibitory modulator, signals within the Stiatal-Thalamic- Frontal loop e.) Enkephalin- a positive modulator signals from the frontal cortex with excitatory input to the Striatum

20 NH 2 Biosynthetic pathway for catecholamines. HO HO HO L-Tyrosine L-Dopa CH 2 C COOH H Tyrosine hydroxylase (Tetrahydrobiopterin, O 2 ) NH 2 CH 2 C COOH H HO DOPA decarboxylase (Pyridoxal phosphate) HO CH 2 CH 2 NH 2 HO Dopamine Dopamine ß-hydroxylase (Ascorbate, O2) HO CHCH 2 NH 2 Norepinephrine HO OH Phenylethanolamine N-methyltransferase S-adenosylmethionine HO CHCH 2 NHCH 3 Epinephrine OH

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22 NeuroImaging relevant to ADHD 1. Right Anterior Prefrontal Cortex Activation during Semantic Monitoring and Working Memory. A.K. MacLeod,et al, Neuroimage 7, Functional Anatomy of Human Auditory Attention Studied with PET. N. Tzourio, et al. Neuroimage 5, A Parametric Study of Prefrontal Cortex Involvement in Human Working Memory. T.S. Braver, et al. Neuroimage 5, 49-62, Neural Corrleates of Planning Ability: Frontal Lobe Activation During The Tower of London Test. R. G. Morris, et al. Neuropsychologia, vov 31 No 12 pp

23 NeuroImaging relevant to ADHD continued 5. Physiological Activation of a Cortical Network During Performance of the Wisconsin Card Sorting Test: A PET Study. K. F. Berman, et al, Neuropsychologia, vol 33, No 8. pp , Brain Morphology in Developmental Dyslexia and Attention Deficit Disorder/ Hyperactivity. G. W.Hynd, et al. Arch Neurol, vol 47, 8-90 pp Attention Deficit Hyperactivity Disorder and Asymmetry of the Caudate Nucleus. G. W. Hynd, et al, Jl Child Neurology/ Vol 8, Oct Ppl Evaluation of Cerebellar Size in ADHD. S. Mostofsky, et al. J. Child Neurol 1998; 13: High Resolution Brain Sect Imaging in ADHD. D. Amen, et al. Annals of Clinical Psychiatry, vol 9, No2, 1997 pp81-85.

24 NeuroImaging relevant to ADHD Continued; 10. Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset. A.J. Zametkin, New England Journal of Medicine, Vol 323,No 20, Nov 15, 1990 Pl SPECT Brain Imaging Abnormalities in ADHD. K. G. Sieg, et al. Clinical Nuclear Medicine. Vol 20,No 1. Pp Jan Frontal Striatum 12 Thalamus 13

25 The Basal Ganglia IV edited by G Percheron et al, Plenum Press, N.Y. 1994

26 Fuster s The Prefrontal Cortex Activation of PFC in Children During a Nonspatial Working Memory Task with Functional MRI PET

27 Neuroimage 2, , 1995; Fuster s fmri slide of working memory fmri

28 Neuroimage slide of PFC in Children during a Nonspatial working memory task with fmri

29 ADHD- Abnormal Response Inhibition 1. Response Inhibition refers to the ability to block the immediate directive to act; motoric, emotional, attentional. 2. Distractibility; failure to Screen Out ongoing stimuli of variable importance. 3. Impulsivity; failure to Filter competing demands to act. 4. Hyperactivity; failure to Inhibit ongoing motor activity 5. Prefrontal Deficits; difficulty with Planning, with Time Management, with keeping the Goal in Mind, Making Sequence Errors, Categorizing super ordinate sets; inadequate Projecting oneself into the Future to access task demand outcome strategies. 6. Boredom

30 DSM IV CRITERIA and UTAH CRITERIA FOR ADHD A. Either (1) or (2) (1) Six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level: A. often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities. B. often has difficulty sustaining attention in tasks or play activities. C. often does not seem to listen when spoken to directly. D. often does not follow through on instruction and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions). E. often has difficulty organizing tasks and activities. F. often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework). G. often loses things necessary for tasks or activities (e.g. toys, school assignments, pencils, books, or tools). H. is often easily distracted by extraneous stimuli. I. is often forgetful in daily activities.

31 DSM IV CRITERIA and UTAH CRITERIA FOR ADHD page 2 (2.) Six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least 6 months to a degree that is maladapative and inconsistent with developmental level: Hyperactivity - often fidgets with hands or feet or squirms in seat. - often leaves seat in classroom or in other situations in which remaining seated is expected. - often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness). - often has difficulty playing or engaging in leisure activities quietly. is often on the go or often acts as if driven by a motor. - often talks excessively. Impulsivity - often blurts out answers before questions have been completed. - often has difficulty awaiting turn. - often interrupts or intrudes on others (e.g. butts into conversations or games). B. Some hyperactive-impulsive or inattention symptoms that caused impairment were Present before age 7 years. C. Some impairment from the symptoms is present in two or more settings (e.g. at school [or work] and at home)

32 DSM IV CRITERIA and UTAH CRITERIA FOR ADHD page 3 D. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning. E. The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g. Mood Disorder, Anxiety Disorder, Dissociative Disorder, or Personality Disorder). Code based on type: ADHD, Combined Type: Both Criteria A1 and A2 are met for the past 6 months ADHD, Predominantly Inattentive Type: Criterion A1 is met, but Criterion A2 is not met for the past 6 months ADHD, Predominantly Hyperactive-Impulsive Type: Criterion A2 is met, but Criterion A1 is not met for the past 6 months. Coding Note: For individuals (especially adolescents and adults) who currently have symptoms that no longer meet full criteria, In Partial Remission should be specified. ADHD, Not Otherwise Specified: There are permanent symptoms of inattention or hyperactivity-impulsivity that do Not meet criteria for ADHD.

33 Evaluation Tools: A Biological-psychological Social Approach. 1. Biological-Defer for now. I recommend SPECT nuclear medicine test. 2. Psychological A) in office; Digit Span, Look Away, Continuous Performance Test, Movement chronometer B) referral to a psychologist; standardized testing; this includes Left and Right Hemisphere assessment and Functions attributed to Frontal functioning. The goal is to define cognitive ability and contrast this with academic level and emotional level of function; WISC III, WAIS, CONNORS, ACTERS, etc. Working memory tests; N-back, CPT

34 Syndrome Imposters and Comorbid Conditions: 1. Learning disorders: reading, math, auditory processing, etc. 2. Epilepsy; primary generalized types include: Occipital, Absence, Frontal. 3. Partial complex epilepsy and non-specific Fronto- Temporal dysrhythmias that are not normal but not epileptogenic. 4. Familial hyperthyroidism 5. Mental Retardation and Borderline Intellectual Functioning 6. Autism; pervasive developmental disorders

35 Syndrome Imposters and Comorbid Conditions continued 7. Major Depression, child, adolescent, young adult,etc. 8. Bipolar Disorder; mixed, depressed, hypomanic 9. Oppositional Defiant Disorder 10. Conduct Disorder 11. Substance Abuse; marijuana, alcohol, etc. 12. Tourette Syndrome; the great masquerader; vocal and motor Tics + OCD and ADHD spectrum.

36 Treatment Rational 1. Identify core vs. comorbid conditions 2. Treat in stages; identify suspected neurotransmitter defect first. 3. Increase online time of circuits involved with processing attention, working memory, affective state. 4. Increase Dopamine (DA) availability in Prefrontal Cortex and Basal Ganglia. DA increase is achieved by A). limiting reuptake via blocking transporter proteins methylphenidate, amphetamine B). increasing its release from the presynaptic cell; dopamine and norepinephrine vescicle - amphetamine

37 Dopamine effects vs. side effects. 1. Attention systems and working memory- PFC, BG 2. Motor movement programs.bg 3. Vascular tone: peripheral 4. Motivation and Impulse systems-ofc 5. Sleep and appetite??? 6. Adverse events: hyperfocusing, irritability, aggression and paranoia; insomnia, anorexia, palpitations and gastric discomfort. 7. Growth suppression: a non issue.

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39 ADHD stimulants: 1. Amphetamine mixed salts; d-amphetamin sulfate, d l-amphetamine sulfate, dl-amphetamine, aspartate,d-amphetamine saccharate. a.) Adderall, Adderall-XR b.) Dexedrine, Dextrostat 2. Methamphetamine 3. Methylphenidate a.) Ritalin, Concerta, Methylin, Metadate Cd 4. Pemoline Non Stimulant based treatment 1. ATOMOXITINE- FDA approval pending for Eli Lilly. Noradrenergic centrally acting medicine.

40 Comorbid Symptoms: Aggression, rapid mood swings, depression, hyperactivity, anxiety, hyperfocusing, obsessing, hypersensitivity to auditory-tactile stimuli. 1. Aggression and hyperactive-impulsive: Clonidine, Tenex 2. Rage, cyclic mood swings: Gabaergic; Depakote, Neurontin, Topamax, Lamictal..Risperidal, Seroquel, Zyprexa 3. Hyperfocussing, obsessing: SSRI s, liquid paxil, celexa, etc. 4. Hypersensitivity: antipsychotics 5. Anxiety states, social phobia: SSRI s 6. Depression: Wellbutrin and Effexor first line then SSRI s

41 Summary: ADHD refers to a core set of symptoms that have a developmental continuum. There is an impact on multiple levels of cognitive and emotional functioning that impair optimal behavior, personality development and social function. Currently the core group of features in this syndrome impacts Attention, Impulse Control and Motor set. A comorbid association of affective features is noted to occur between 10 and 40 %. The model of Working Memory and Response Inhibition Failure approximates the deficits across multiple domains based on the current understanding of brain function.

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