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  • MTA

    1. 1. Peter S. Jensen, M.D. ~Putting Science to Work~ Center for the Advancement of Children’s Mental Health Columbia University Beyond DSM-IV: New Models for Understanding and Diagnosis of Children’s Emotional and Behavioral Problems
    2. 3. Myths Surrounding The Causes Of Childhood Psychiatric Disorders Bad parenting They'll grow out of it food additives cause these disorders bad diet
    3. 4. Family Environment The Child’s Inner Environment Social Environment Physical Environment Child Health Child’s Health Policy
    4. 5. Behavior Biology Physical Environment Child Health Policy Birth Early Adult Time Development Child’s Health Health Services Social Environment (Culture Family Community)
    5. 7. Synaptic density/mm 3 x 10 6
    6. 8. Greenough, et al., 1998
    7. 9. ADHD as a Case Example
    8. 10. ADHD Historical Timeline 1900 1937 1955 1960 1966 1980 1987 1994 Bradley; Benzedrine MPH created Clements listed attention as a deficit in children Attention Deficit Hyperactivity Disorder (DSM-III-R) DSM-IV updated criteria Attention Deficit Disorder + or – Hyperactivity (DSM-III) Minimal Brain Dysfunction George Still described ADHD symptoms Bradley (1937)—original conceptualization of ADHD involved testing of response to stimulant.
    9. 11. ADHD: Proposed Etiologies <ul><li>Neuroanatomic, neurochemical 1 </li></ul><ul><li>Genetics 2 </li></ul><ul><li>CNS injury 3 </li></ul><ul><li>Environmental risk factors 4 </li></ul>1. Swanson J et al. Curr Opin Neurobiol . 1998;8:263-271. 2. Hauser P et al. N Engl J Med. 1993;328:997-1001. Cook EH et al. Am J Hum Genet . 1995;56:993-998. Swanson JM et al. Mol Psychiatry. 1998;3:38-41. 3. Milberger S et al. Biol Psychiatry. 1997;41:65-75. 4. Castellanos FX et al. Arch Gen Psychiatry . 1996;53:607-616. Swanson JM et al. Lancet. 1998;351:429-433. 4
    10. 12. Scientific American , September 1998 ADHD: Suggested Pathophysiology
    11. 13. ADHD Adult vs. Normal Controls (fMRI During Perceptual Task)* ADHD *Stroop task utilized MGH-NIMR Center & Harvard-MIT CITP, Bush G et al. Biol Psychiatry. 1999 ADHD brain uses less efficient pathway to process data NORMAL
    12. 14. Twin Studies Show ADHD Is a Genetic Disorder Faraone. J Am Acad Child Adolesc Psychiatry. 2000;39:1455-1457. Hemminki. Mutat Res. 2001;25:11-21. Palmer. Eur Resp J. 2001;17:696-702. Willerman, 1973 Goodman, 1989 Gillis, 1992 Edelbrock, 1992 Schmitz, 1995 Thapar, 1995 Gjone, 1996 Silberg, 1996 Sherman, 1997 Levy, 1997 Nadder, 1998 Hudziak, 2000 Average genetic contribution of ADHD based on twin studies Height Breast cancer Asthma Schizophrenia ADHD Mean 0 0.2 0.4 0.6 0.8 1
    13. 15. Is ADHD a Real Problem? <ul><li>NIH Consensus Conference on ADHD (1998): </li></ul><ul><ul><li>“ ADHD is a severe public health problem...” </li></ul></ul><ul><ul><li>not a “U.S.-only problem,” but found in all countries in similar rates everywhere studied </li></ul></ul><ul><li>Council of Europe (EEU) Conference Findings (2000) </li></ul><ul><ul><li>ADHD a major problem in member countries </li></ul></ul><ul><ul><li>under-recognized and under-treated by a factor of 10 to 1 </li></ul></ul>
    14. 16. Are Children Just Being “Labeled?” Attention Problems in Classroom Children
    15. 17. Assessment Points Baseline Early Treatment (3 m) Mid- treatment (9 m) End Treatment (14 m) Follow-up (24 m) Follow-up (36 m) 14-m Treatment Stage 10-m Follow- up After Treatment 22-m Follow- up After Treatment 0 36 24 14 Month Recruitment Screening Diagnosis Random Assignment 579 ADHD Subjects Medication Only 144 Subjects Psychosocial (Behavioral) Treatment Only 144 Subjects Combined Medication and Psychosocial Treatment 145 Subjects Assessment and Referral (Community Control) No Treatment from Study; Assessed for 24 mo. 146 Subjects Recruitment of LNCG Cohort
    16. 18. Class 1 Over Time
    17. 19. Class 2 Over Time
    18. 20. Class 3 Over Time
    19. 21. Treatment Effectiveness at 24 Months by Class and Med Status
    20. 23. Non-Genetic Causes of ADHD <ul><li>Fetal distress (Lou (1996), Biederman et al. 1994) </li></ul><ul><li>Fetal distress + subsequent adversity (Werner & Smith, 1980) </li></ul><ul><li>Traumatic brain injury (Max et al, 1998; Gerring et al, 1998) </li></ul><ul><li>Tobacco Use </li></ul><ul><li>Lead Exposure </li></ul><ul><li>Psychosocial adversity </li></ul><ul><li>Causes vs. Correlates? </li></ul><ul><li>etc. </li></ul>
    21. 24. Challenges and Opportunities in Etiologic Understanding 4 <ul><li>Dysregulation of inhibitory frontocortical activity (predominantly noradrenergic) on striatal structures (predominantly dopaminergic, leading to deficits in response inhibition and executive function </li></ul><ul><li>Efficacy of noradrenergic and dopaminergic agents suggests these neurotransmitters play role </li></ul><ul><li>Other brain regions likely involved (cerebellum) </li></ul><ul><li>Etiology remains unknown, correlational studies only (e.g., in neuroimaging Durston, Buitelaar, 2004 ) </li></ul><ul><li>Known candidate genes account for tiny fraction </li></ul><ul><li>Need for prevention and early intervention studies </li></ul>Zametkin. J Am Acad Child Adolesc Psychiatry 1987; Pliszka SR et al. J Am Acad Child Adolesc Psychiatry 1996;35:264-272.
    22. 25. Rethinking ADHD <ul><li>Deficit, Disorder, or “Adaptive Problem?” </li></ul><ul><li>What is the Adaptive Problem? </li></ul><ul><li>Within-individual (neural plasticity) and within-species “adaptation” (allelic variation) </li></ul><ul><li>Developmental and Timing Considerations </li></ul>
    23. 26. Evidentiary Considerations: Adaptability/Enhanced Survival <ul><li>Motoric behavior </li></ul><ul><ul><li>“ sitter” fly gene </li></ul></ul><ul><ul><li>increased motoric behavior in young across mammalian species - why? </li></ul></ul><ul><li>Attentional/Scanning mechanisms </li></ul><ul><ul><li>Role of vigilance in survival - predator/prey relations, food and resource availability </li></ul></ul><ul><ul><li>Noise stress impairs primate PFC delayed (but not immediate) responses - PFC “off-line”, automatic responses take over (Arnsten & Rakic, 1998) </li></ul></ul><ul><li>Impulsivity </li></ul><ul><ul><li>“ Trading speed for accuracy” - “fast-guess” model fits inattentives but not hyperactives (Sergeant & Scholten, 1985) </li></ul></ul>
    24. 27. ADHD symptoms as an Adaptive Problem
    25. 28. Genetic Roots
    26. 29. Evidentiary Considerations: Plasticity/Malleability <ul><li>Experience-expectant, Experience-dependent, Activity-dependent processes </li></ul><ul><ul><li>“ Sensitive” vs. “Critical” Periods </li></ul></ul><ul><li>Basic Science Evidence: </li></ul><ul><ul><li>Plasticity of LC tuning and gating processes (single LC neurons, rat model) (Sara & Segal, 1991) </li></ul></ul><ul><ul><li>Scanning behavior (human) - (Fisch & McNamara, 1964) </li></ul></ul><ul><ul><li>Selection of learning modality can be shaped (Warren & Schmidt, 1978) </li></ul></ul><ul><ul><li>Analogues across most systems studied </li></ul></ul>
    27. 30. Evidentiary Considerations: Plasticity/Malleability (cont.) <ul><li>Clinical evidence from stress/trauma/development: </li></ul><ul><ul><li>Glod & Teicher, 1996 (abused children w/10% increases in activity, fewer low-activity periods </li></ul></ul><ul><ul><li>Jensen, 1989; Cuffe et al., 1994 - hyperarousal induced by trauma, hypervigilance, poor concentration -> ADHD syndrome </li></ul></ul><ul><ul><li>Christakis et al., 2004, NLSY, N=1,278: Early television exposure (age 1 & 3) positively related to increased hyperactivity at age 7. </li></ul></ul><ul><ul><li>1970 British Cohort Study (BCS70). N=16,151, followed at ages 5, 10, 16, 26, and 30: Compensatory hyperactivity “protected” children from low-maternal stimulation homes, vis-à-vis educational attainment. </li></ul></ul><ul><ul><li>Sonuga-Barke et al., 2002 – stronger, more enduring effects of BT on younger children </li></ul></ul>
    28. 31. Evidentiary Considerations: Contextual Factors <ul><li>Differences between ADHD and non-ADHD children relatively context-specific - homework and play conditions (Zentall, 1984) </li></ul><ul><li>Arises in context of early experiences, maintained by later experiences </li></ul><ul><ul><li>Jacobowitz & Sroufe, 1987 - theory of arousal modulation (2 of 3 factors predictive of KG hyperactivity -- intrusiveness, overstimulation, 6 months - 3 1/2 years) (2 of 38 factors) </li></ul></ul><ul><ul><li>Lambert & Hartsough, 1984 - early temperamental factors and family environment </li></ul></ul><ul><ul><li>Family adversity predictive of persistent ADHD, Biederman et al., 1995, Rutter et al., 2003 </li></ul></ul>
    29. 32. Evidentiary Considerations: Contextual Factors (cont.) <ul><li>Twin Studies - Role of genes and environment - unexplained variance </li></ul><ul><ul><li>Sherman et al., 1997; Thapar et al, 1995; Nadder et al, 1998; Levy et al., 1997; Hudziak et al., 1998 </li></ul></ul><ul><li>Permissive Role of Environmental Factors in Gene-environment interactions </li></ul>
    30. 33. Extent of Mental & SU Disorders In U.S. Children and Adolescents 7.8% 8.0% 5.6% 5.0% 7.7% 0.5% Source: Office of the Surgeon General, and National Institute of Mental Health, 1999
    31. 34. To Diagnose or to Not Diagnose? “labeling?”
    32. 35. Why and How Do Doctors “Diagnose?” <ul><li>Science (and medicine) impossible without diagnosis </li></ul><ul><li>Historically, classification systems have been based on: </li></ul><ul><ul><li>externally observable descriptions: similarity in outward appearance - Adanson, 1763 </li></ul></ul><ul><ul><li>internal structures - inner workings and mechanisms - Cuvier, 1835 </li></ul></ul><ul><ul><li>evolutionary-genetic relationships - Darwin, 1856 </li></ul></ul><ul><ul><li>purpose of the classification system - Dupre, 1993 </li></ul></ul><ul><li>Diagnostic and Statistical Manual (e.g, DSM-IV) </li></ul><ul><li>International Classification of Diseases (e.g., ICD-10) </li></ul>
    33. 36. Purposes and Uses of Classification and Diagnosis <ul><li>Current purposes of Classification </li></ul><ul><ul><li>denomination (putting a name on things) and efficiency of communication </li></ul></ul><ul><ul><li>qualification (adding more information to the name ) </li></ul></ul><ul><ul><li>prediction (course, response to treatment, outcome) </li></ul></ul><ul><ul><li>ultimate test is usefulness </li></ul></ul><ul><li>How diagnoses are used </li></ul><ul><ul><li>allocation of resources - to determine who should receive care </li></ul></ul><ul><ul><li>scientific purposes - to efficiently describe and communicate to others so that knowledge can be advanced </li></ul></ul>
    34. 37. What’s In a Name? <ul><li>Principles Often Used for Diagnosis: </li></ul><ul><ul><li>Structural pathology (ulcerative colitis) </li></ul></ul><ul><ul><li>Subjective nature of symptom presentation (migraine headache) </li></ul></ul><ul><ul><li>Deviance from a physiologic norm (hypertension) </li></ul></ul><ul><ul><li>Known causes (e.g., HIV, sickle cell anemia) </li></ul></ul><ul><ul><li>Symptoms plus impairment (mental disorders) </li></ul></ul><ul><ul><li>Cause plus symptom pattern (substance-induced psychosis) </li></ul></ul><ul><ul><li>Onset, course, and/or outcome </li></ul></ul><ul><ul><li>Other combinations </li></ul></ul>
    35. 38. What’s In a Name? Let the Buyer Beware! <ul><li>All diseases are “temporary constructions” </li></ul><ul><ul><li>Shaped by current norms and values </li></ul></ul><ul><ul><li>Undergo progressive refinement with scientific advances </li></ul></ul><ul><ul><ul><li>cholera - bad humors, elevation, dampness, Broad Street pump, discovery of cholera bacteria, antibiotics </li></ul></ul></ul><ul><ul><ul><li>HIV - Kaposi’s sarcoma, human immunodeficiency syndrome, HIV discovery </li></ul></ul></ul><ul><ul><ul><li>ulcers - excess stomach acid vs. bacterium H. pylori </li></ul></ul></ul><ul><ul><li>Prevention/intervention sometimes possible before known of causes: vitamin deficiency syndromes </li></ul></ul>
    36. 39. What’s In a Name? <ul><li>Parallels between psychiatry and other areas of medicine: </li></ul><ul><ul><li>Psychiatric diagnosis principally reliant on </li></ul></ul><ul><ul><ul><li>symptoms and symptom patterns </li></ul></ul></ul><ul><ul><ul><li>severity </li></ul></ul></ul><ul><ul><ul><li>duration of symptoms </li></ul></ul></ul><ul><ul><ul><li>associated features, e.g., age of onset </li></ul></ul></ul><ul><ul><ul><li>eliminating (“ruling out”) possibility of other known causes during diagnostic process </li></ul></ul></ul><ul><ul><li>Juvenile rheumatoid arthritis </li></ul></ul><ul><ul><li>Benign essential hypertension </li></ul></ul>
    37. 40. Benefits of Diagnosis <ul><li>Why It is Important: </li></ul><ul><ul><li>Before treatment begins, it is important to have a correct diagnosis from a trained professional in order to: </li></ul></ul><ul><ul><ul><li>Determine a course of treatment </li></ul></ul></ul><ul><ul><ul><li>Plan for treatment monitoring </li></ul></ul></ul><ul><ul><ul><li>Link treatment to prognosis </li></ul></ul></ul><ul><ul><ul><li>Become eligible for special education services </li></ul></ul></ul><ul><ul><ul><li>Determine co-occuring problems </li></ul></ul></ul><ul><ul><ul><li>“ Do no harm” – avoid unnecessary or dangerous treatment </li></ul></ul></ul><ul><ul><li>Communication with other professionals </li></ul></ul><ul><ul><li>Relief in having a “name” for family </li></ul></ul><ul><ul><li>Help client get “psychological distance” on the problem, enhance relationship </li></ul></ul>
    38. 41. To Diagnose or to Not Diagnose? <ul><li>BUT: Diagnosis Alone Insufficient </li></ul><ul><ul><li>behavior develops as a continuing, complex, multi-layered interaction between person and environment (contextual-ecological perspective) </li></ul></ul><ul><ul><li>“ history matters” - brought forward in the life of the individual </li></ul></ul><ul><ul><li>diagnosis without dehumanizing…keep the child/person in the equation – focus on STRENGTHS! </li></ul></ul><ul><ul><li>problem is NOT diagnosis/labeling, but stigma and lack of resources for children in need </li></ul></ul><ul><ul><li>specificity/accuracy vs. “grab-bags” (SED) </li></ul></ul>
    39. 43. Treatment Considerations <ul><li>Scientifically Supported Treatments : </li></ul><ul><ul><li>ADHD: 200+ medication studies, 80+ psychotherapy studies </li></ul></ul><ul><ul><li>Depression: 1 medication (+/-), 2 forms of psychotherapy </li></ul></ul><ul><ul><li>SUD: 1 psychotherapy </li></ul></ul><ul><ul><li>Anxiety Disorders: 4 medications , 1 psychotherapy </li></ul></ul><ul><ul><li>Conduct disorders: 3 medications , 1 psychotherapy </li></ul></ul><ul><ul><li>Autism: 2 medications , 1 psychotherapy </li></ul></ul>
    40. 44. MISLEADING DICHOTOMIES Brain vs. Behavior? Nature vs. Nurture?
    41. 46. <ul><li>Additional research needed that meets highest standards of methodologic rigor to answer questions definitively </li></ul><ul><li>Studies that combine information about symptoms, clinical course, family history with </li></ul><ul><ul><li>Neuroimaging </li></ul></ul><ul><ul><li>Genetic markers </li></ul></ul><ul><ul><li>Treatment response </li></ul></ul><ul><li>Humility - avoid overstating your case! </li></ul><ul><li>Keep the discussion scientific, rather than political or personal </li></ul>Diagnostic Controversies: Recommendations for Clinicians & Scientists
    42. 47. <ul><li>When scientists are quibbling among themselves: Don’t take sides -- instead, demand more, better research: Current situation is not acceptable! </li></ul><ul><li>Become Research-savvy: </li></ul><ul><ul><li>;, </li></ul></ul><ul><li>Be skeptical: “In God We Trust….but from all others, demand data!” </li></ul><ul><li>Understand temporary nature of current diagnostic systems: Look for (and insist upon) further advances. A name is only a name, if not linked to treatment understanding and outcomes </li></ul>Diagnostic Controversies: Recommendations for Parents