Assessment and Diagnosis of ADHD

Transcription

1 Assessment and Diagnosis of ADHD Joseph Biederman, MD Professor of Psychiatry Harvard Medical School Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD Director, Bressler Program for Autism Spectrum Disorders Massachusetts General Hospital

2 History of ADHD 1937 Bradley* Benzedrine George Still described ADHD Symptoms 1955 MPH Created 1960 Minimal Brain Dysfunction 1987 Attention Deficit Hyperactivity Disorder (DSM-III-R) 1966 Clements listed attention as a deficit in children 1980 Attention Deficit Disorder + or Hyperactivity (DSM-III) 1994 DSM-IV updated criteria 2013 DSM-V updated * Bradley (1937) original conceptualization of ADHD involved testing of response stimulant. criteria American Psychiatric Association, 1980, 1987, 2001; Bax M, MacKeith R. London: Heinemann; 1963; Bradley C. Am J Psychiatry 1937;94:577-85; Pediatrics 1950;5:24-37; Clements SD. J Lancet 1966;86: Editorial, J Atten Disord 2000;3: Still GF. Lancet 1902;1: , , ; Stubbe DE. Child Adolesc Psychiatr Clin N Am 2000;9:

3 ADHD: Etiology ADHD is a heterogeneous behavioral disorder with multiple possible etiologies NeuroanatomicNeuroch emical Genetic origins ADHD CNS insults Environmental factors

4 Worldwide Prevalence of ADHD in Children N.Y., Mich., Wis. North Carolina Virginia Missouri Oregon Minnesota Tennessee Iowa Pittsburgh New York City Puerto Rico USA Prevalence of ADHD (%) Faraone SV et al. (2003), World Psychiatry 2(2): Spain New Zealand Canada Ireland United Kingdom Israel Switzerland Netherlands/Belgium Germany Ukraine Brazil Japan New Zealand Netherlands China India Ex USA Prevalence of ADHD (%)

5 Akinbami et al. NCHS Data Brief No. 70, August 2011

6 Psychopharmacology Course 2017 Zuvekas al. Am J Psychiatry 2012; 169:

7 Patients (%) Adherence in ADHD is Dismal Only 13% of patients consistently take their medication one year out 100% 80% 60% 40% 20% OROS MPH MPH LA MAS XR Atomoxetine Within 2 to 3 months, a majority of patients with ADHD have stopped taking medication consistently Patients renewed their monthly prescriptions about 2 to 3 times per year 1 0% Month Psychopharmacology Course 2017

8 Percent of Children with ADHD who Renewed their First Stimulant Rx at Partners Healthcare: An EMR Review Percent (%) # of patients # of patients who refilled a prescription for 1 medication % of patients who refilled 2, 685 1, % Patients who refilled a prescription for 1 medication

9 Poor Adherence to Treatment in ADHD Poor adherence occurs despite the well documented morbidity of ADHD, the marked efficacy and safety of stimulants as well as the fact that ADHD symptoms return rapidly when the medication is not taken Psychopharmacology Course 2017

10 Long Delays in the Initiation of Treatment (n=1498) p < Age of Onset of Diagnosis Age of Onset of Treatment MGH Pediatric Psychopharmacology Clinic

11 Diagnosis of ADHD Diagnosis is based on clinical assessment of symptoms, associated impairment and age of onset No test is available Symptoms are subjective, as well as developmentally and context sensitive

12 ADHD: Core Symptom Areas Inattention Impulsivity/Hyperactivity Psychopharmacology Course 2017

13 ADHD: DSM-V Criteria Inattention Six or more of the following manifested often: Inattention to details/ makes careless mistakes Difficulty sustaining attention Seems not to listen Fails to finish tasks Difficulty organizing Avoids tasks requiring sustained attention Loses things Easily distracted Forgetful DSM-V, 2013

14 ADHD: DSM-V Criteria Impulsivity/Hyperactivity Six or more of the following manifested often: Impulsivity Blurts out answer before question is finished Difficulty awaiting turn Interrupts or intrudes on others Hyperactivity Fidgets Unable to stay seated Inappropriate running/climbing (restlessness) Difficulty in engaging in leisure activities quietly On the go Talks excessively

15 ADHD Variation in Symptoms Pervasiveness Symptoms Vary in Frequency of Occurrence Degree of Impairment

16 Course of ADHD Symptoms Over Time by Sex: A Growth Curve Model Age by Sex Interaction: NS Psychopharmacology Course 2017 Biederman et al. 2009

17 Age-Dependent Decline and Persistence of ADHD Throughout the Lifetime Psychopharmacology Course 2017 Faraone et al. Nature Reviews Disease Primers 2015

18 ADHD: Course of the Disorder Hyperactivity Impulsivity Inattention Time Psychopharmacology Course 2017

19 ADHD as a Brain Disorder

20 Psychopharmacology Course 2017 Faraone et al. Nature Reviews Disease Primers 2015

21 The DLPC is linked to WM, the VMPFC to complex decision making and strategic planning, and the parietal cortex to attention Faraone et al. Nature Reviews Disease Primers 2015 Brain Mechanisms in ADHD The executive control and cortico-cerebellar networks coordinate EFs The VMPFC, OFC & ventral striatum are the brain network associated with anticipation and reward Psychopharmacology Course 2017 The frontal and parietal cortices and the thalamus support attentional functioning Negative correlations between the DMN and the frontoparietal control network are weaker in patients with ADHD

22 Hoogman at el. (ENIGMA ADHD Working Group) Lancet Psychiatry 2017 Feb 16. doi: /S (17) Psychopharmacology Course 2017

23 Psychopharmacology Course 2017

24 ADHD Imaging Studies Summary Neuroimaging studies confirm that brain abnormalities in fronto-subcortical networks are associated with ADHD Neuroimaging techniques are not valid tools for ADHD diagnosis; imaging measures are not sensitive or specific enough to be used for diagnostic purposes Treatment attenuates neural deficits Spencer et al. J Clin Psychiatry 2013 Sep;74(9):902-17

25 ADHD as Neurobiological Disorder Catecholamine Dysregulation

26 Frontosubcortical Networks and Catecholamines Dopaminergic and noradrenergic dysregulation abnormalities in fronto subcortical pathways Medications that are effective in ADHD are either dopaminergic or noradrenergic Zametkin. J Am Acad Child Adolesc Psychiatry. 1987;26(5): Zametkin. J Am Acad Child Adolesc Psychiatry. 1987;26(5):

27 Human Brain From R. Barkley, Scientific American, Sept. 1998, p. 47

28 Brain Stem to diencephalon and cerebrum Substantia nigra tegmentum (dopamine) MESENCEPHALON to cerebellum Locus ceruleus (norepinephrine) PONS Raphe nuclei (serotonin) Psychopharmacology Course 2017 to cord MEDULLA

29 Psychopharmacology Course 2017

30 Business Week, 1999

31 ADHD: Genetics Twin Studies Family Studies Genetic Basis of ADHD Adoption Studies Molecular Genetics

32 Family Studies Biederman et al (1990) ADHD in first-degree family members of children with ADHD ADHD group Control group Cantwell (1972) Morrison & Stewart (1971) Percent

33 Panic Disorder Schizophrenia Height Illott 2010 Bornovalova 2010 Cole 2009 Laarson 2004 Rietveld 2003 Martin 2002 Kuntsi 2001 Coolidge 2000 Thapar 2000 Willcutt 2000 Hudziak 2000 Nadder 1998 Levy 1997 Sherman 1997 Silberg 1996 Gjone 1996 Thapar 1995 Schmitz 1995 Stevenson 1992 Edelbrock 1992 Gillis 1992 Goodman 1989 Willerman 1973 Matheny Heritability Mean Heritability of ADHD in Youth=.75

34 Genetics of ADHD Psychopharmacology Course 2017 Faraone et al. Nature Reviews Disease Primers 2015

35 The Dopamine Story... Presynaptic Neuron Dopamine Transporter (DAT) Dopamine Methylphenidate (MPH) Dopamine Receptor (DRD4) Psychopharmacology Course 2017

36 0 10,000 20,000 30,000 40,000 New Results from Genomewide Association Studies (GWAS) Number of ADHD GWAS Samples sychopharmacology Course 2017 Y2012 Y2014 Q4_2015 Q1_2019 Faraone et al, 2015

37 Preliminary ADHD meta-analysis 18,284 cases 33,836 controls Preliminary analyses suggest eight genome-wide significant loci Psychopharmacology Course 2017 PGC ADHD/iPSYCH-SSI-Broad Collaboration

38 History of Maternal Smoking (%) Maternal Smoking During Pregnancy: Results in Children % P=0.002 * P=0.04, controlling for SES, parental ADHD, and parental IQ % 5 0 ADHD ( N=140) Controls ( N=120) Milberger et al. Am J Psychiatry 1996;153:1138.

39 ADHD Diagnostic Considerations Inattention Impulsivity/Hyperactivity

40 Cumulative Morbidity Risk Cumulative Morbidity Risks for Psychiatric Disorders in ADHD and Control Probands Control ADHD P.009 for all categories Biederman et al. Psychological Medicine, 2006, 36,

41 Psychopharmacology Course 2017 Biederman et al. AJP. April 2010

42 Probability of Accident Accidents and Near Misses 80% P<0.05* 70% P<0.05* 60% 50% 40% ADHD ADHD 30% 20% 10% 0% Accident Accident and Near Misses *Indicates P<0.05 after controlling for gender, age, time of day and the age*adhd interaction (Reimer et al., submitted)

43 Percent of Subjects Involved in Collisions During Surprise Events * LDX = lisdexamfetamine dimesylate During the five surprise events, drivers in the medication group were 67% less likely to have a collision than drivers in the placebo group Biederman et al submitted

44 Chang et al. JAMA Psychiatry. doi: /jamapsychiatry Published online May 10, 2017.

45 ADHD: Impact on Family Parents of children with ADHD experience higher levels of Stress Self-blame Social isolation Depression Marital discord Mash and Johnston. J Clin Child Psychol 1990;19:313. Murphy and Barkley. Am J Orthopsychiatry 1996;66:93.

46 Status of 144 Caregivers at any time after Diagnosis of Child s ADHD Changed Work Status 39% Unchanged Work Status 63% Noe et al. 1999

47 Impairment in ADHD Psychiatric comorbidity School failure Poor peer relationships Legal difficulties Smoking and substance abuse Accidents and injuries Family conflict Parent stress

48 Is ADHD a Serious Public Health Prevalence Concern? Impairment Treatment Effectiveness Public Health Significance Chronicity

49 Summary ADHD is a neurobehavioral disorder with a: Complex etiology Neurobiologic basis Strong genetic component ADHD Affects millions of people of both genders Persists through adolescence and adulthood in a high percentage of cases Can have negative impact on multiple areas of functioning ADHD is a highly treatable disorder

50 QUESTIONS?