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兒童青少年精神疾病 台北榮民總醫院 精神部兒童青少年精神科主任 陳映雪醫師 Disorders usually first diagnosed in infancy, childhood, and adolescence Mental retardation Reading, math, writing Motor skills disorder Communication disorders Elimination disorders Pervasive developmental disorders Attention deficit and disruptive behavior disorders ADHD ODD CD Tic disorder / Tourette’s disorder Feeding and eating disorders Child abuse and neglect Temperament problems 北榮陳映雪 Anxiety disorders separation anxiety disorder selective mutism Specific phobia School phobia Social phobia OCD PTSD Learning disorders Borderline intellectual function Eating disorders Schizophrenia Mood disorders Bipolar disorder Dysthymia major depression Substance abuse Disruptive behavior disorders Attention deficit hyperactive dsorder (ADHD) Oppositional-defiant disorder (ODD) Conduct disorder (CD) ADHD DSM-IV診斷標準 A. 核心症狀 1.注意力差 2.好動 3.衝動 學習問題 行為問題、人際衝突、易發生意外、 青少年時期車禍多 *持續六個月以上 B. 於七歲之前就有的症狀 C. 至少在兩種情境呈現症狀 D. 造成社會生活功能障礙 E. 無法由 其它精神疾病來解釋 ADHD DSM-IV 診斷標準 A. 具有下列(一)或(二)之一達六個月以上 與發展程度比較的不適應症狀 (一) Inattention(無法專心)(6項以上) 1) 2) 3) 4) 5) 6) 7) 8) 9) 常粗心大意或無法注意細節 (功課或工作上) 工作或遊戲注意力無法持久 別人跟他講話,經常不注意聽 無法遵守指示完成功課或工作 安排工作或活動常發生困難 常常逃避或拒絕需要持續精神(用功)的工作 遺忘帶需要的東西 容易被外界轉移注意力 日常生活中經常遺忘每天該作的事 ADHD DSM-IV 診斷標準 (二) Hyperactivity-impulsivity:(6項以上) Hyperactivity (過動) 5. 手腳亂動, 坐著也扭來扭去 無法安靜坐著或常離座 (教室) 常過度的跑來跑去,或爬上爬下 無法安靜遊戲 不停的動,精力過盛 6. 話很多 1. 2. 3. 4. Impulsivity (衝動) 1. 話未問完,就搶著回答 2. 缺乏耐心等待 3. 常干擾別人 Impulsivity Behavior that is swayed by emotional or involuntary impulses Behavior without adequate forethought Tendency ot choose immediate over long term rewards Engagement in behaviors that are likely to be punished. Persistent reward-seeking behaviors 北榮陳映雪 Type of ADHD Predominantly Inattentive Type (ADD) 注意力不集中型 Predominantly Hyperactive-Impulsive Type 過動衝動型 Combined Type 結合型 (1+2) For individuals (especially adolescents and adults) who currently have symptoms that no longer meet full criteria, "In Partial Remission" should be specified. (adult ADD) 北榮陳映雪 ADHD共病疾病 對立異常症 (oppositional defiant disorder) 56% 反社會規範異常症 (conduct disorder) 31% 學習障礙症 (learning disorder) 25% 溝通障礙 (communicative disorder) 20% 遺尿症 (enuresis) 6% 焦慮症 (anxiety disorder) 20% 單純性畏懼症 (simple phobia) 9% 社會畏懼症 (social phobia) 3% 重鬱症 (major depressive disorder) 6% 雙相性情感性疾患 (bipolar disorder) 6% 托倫氏症 (Tourette’s disorder) 3% Comorbidity of Psychiatric disorders in ADHD 4% 40%/14% 11% 34% 北榮陳映雪 ADHD vs. ADD Gender : ADHD: boys > girls ADD: girls >boys Age of being detected: ADHD<ADD Clinical manifestation: ADHD: more behavior problem & ODD or CD Self-regulation deficit + selective attention problem ADD: more academic problem & LD selective attention problem more social withdrawn 北榮陳映雪 Self Regulation Sustained attention Inhibitory control over behavior Capacity to delay gratification Ability to suppress strong emotion 北榮陳映雪 Diagnosis of ADHD (I) Clinical interview (only way to establish Diagnosis) Hx from parents/caretakers Review school information School reports, LD? Rating scales (teacher) Explore parent teacher relationship Document signs & symptoms Age of onset Duration Different settings Physical exam 北榮陳映雪 Diagnosis of ADHD (2) Meets DSM-IV or ICD-10 criteria Screen for comorbid disorders Psychological assessments IQ test, Attention test, Personality test For detect individual strength and weakness for counseling. 北榮陳映雪 Prevalence for ADHD in Children About 3 to 10 % Increasing prevalence from DSM-III (9.6%) to DSM-III-R (10.9%, 7.3%) to DSM-IV (17.8%, 11.4%) More frequent in boys than in girls (3-4:1) 北榮陳映雪 Prevalence in adolescence & adults No. and severity of symptoms declines with age. Prevalence in Adolescents: 2-6% No Gender difference The National Comorbidity Study (USA) suggest a prevalence of 4.7% or more in adults 北榮陳映雪 Prognosis of ADHD ADHD grown up 1/3: remission 1/3: adult ADD with residual symptom (inattentive, impulsive), 1/3: associated with conduct disorder (drug abuse, antisocial behavior, injuries of all sorts) poorer educational performance and were underachiever 北榮陳映雪 Age-Specific Prevalence of ADHD Remission : DSM-III-R ADHD Percent Remitting Diagnosis 100 90 80 70 Syndromatic Symptomatic Function 60 50 40 30 20 10 0 <6 Biederman et al. 2001 6-8 9-11 12-14 Age 北榮陳映雪 15-17 18-20 北榮陳映雪 Adult ADHD: Psychiatric Comorbidity % comorbid condition 50 45 40 35 30 25 20 15 10 5 0 Substances Depression Anxiety Bipolar Learning disabilities Biederman, Am J Psychiatry, 1993; 150(12): 1792-1798. 北榮陳映雪 Antisocial Predictors of Persistence of ADHD Risk for ADHD in Probands P < 0.001 Risk Factors: Odds Ratio 8 7 6 5 4 3 2 1 0 1. Family History of ADHD 2. Co-morbidity 3. Adversity 1 2 Number of Risk Factors Beiderman et al, 1995 (N=128) 北榮陳映雪 3 ADHD發展成 對立異常症或行為障礙症因素 生物性因素 父母管教方式 環境因素 無藥 物 治療 對立異常症 注意力缺損 過動症 行為障礙症 學習問題 人際互動問題 北榮陳映雪 北榮陳映雪 Etiologies of ADHD From Joel Nigg (2006), What Causes ADHD? Perinatal Other Smoking Lead FASD LBW Heritable (Genetics) 北榮陳映雪 Heritable LBW FASD Lead (high) Smoking Perinatal Other (Toxins) Etiology of ADHD I. Genetic twin studies showing a mean heritability of 0.8 polygenic disorder (catecholamine system) DRD4, DAT1, DRD5, DRD1, serotonin receptor (5HTR) 2A, 5HTR1B, synaptosomal associated protein of 25 kD (SNAP-25) Delay maturation of brain Minimal brain dysfunctions (MBD) Fetal exposure to Maternal abuse of alcohol, smoking, drug, Pregnancy complication or birth trauma Toxins (mercury, lead, manganese) 北榮陳映雪 北榮陳映雪 北榮陳映雪 ADHD:Molecular Genetics Genes implicated by several studies: DRD4, DRD5, 5HT1B No single gene causes ADHD The genes likely combine with each other and environmental risk factors to cause ADHD Smalley, Am J Hum Genet. 2002;71(4):959-963. 北榮陳映雪 北榮陳映雪 Etiology of ADHD II. Delay maturation of brain Minimal brain dysfunctions (MBD) Fetal exposure to Maternal abuse of alcohol, smoking, drug, Pregnancy complication or birth trauma Toxins (mercury, lead, manganese, PCB) 北榮陳映雪 北榮陳映雪 北榮陳映雪 Etiology of ADHD III. Gene – Environment Interaction Chaotic family environments Poor parenting skills 北榮陳映雪 北榮陳映雪 北榮陳映雪 Pathophysiology of ADHD Dysfunction of the catecholamine system Wender P(1971) : dysfunction in DA and NE Levy F (1991): dopamine deficit theory. Volkow et al (1998): methylphenidate : blockade DA transporter. (PET) Pathophysiological findings: No. of DAT binding sites is higher in drug-naive patients. Decrease in DOPA decarboxylase activity in the prefrontal cortex, primary deficits in subcortical dopamine systems. Complex dysregulation of DA neurotransmitter system 北榮陳映雪 Both genetic and environmental risk factors have small, addictive and interactive effects on the probability a child will develop ADHD 北榮陳映雪 北榮陳映雪 Brain imaging studies (Mid 1990s-) Anatomic abnormalities in specific brain regions where dopamine receptors are dense. reduced size of right frontal lobe and caudate nucleus A 10-year study by (NIMH) : brains are 3-4% smaller than normal ( pharmacologic treatment is not the cause) The more severe ADHD symptoms, the smaller frontal lobes, temporal gray matter, caudate nucleus, and cerebellum were. 北榮陳映雪 Grey Matter Difference Maps (A) and Statistical Maps (B) in Children with ADHD and Controls ADHD subjects show a 20–30% increase in greymatter density in bilateral temporal & inferior parietal 北榮陳映雪 Sowell et al., 2003 regions Working Memory Related Changes In Adults with ADHD – Compensation? HC > ADHD Control group demonstrates WM activation associated with verbal rehearsal strategies & inhibitory control ADHD > HC ADHD group demonstrates WM activation associated with motor & visual processing suggestive of compensatory brain regions and strategies. Schweitzer et al, Biological Psychiatry, 2004 北榮陳映雪 北榮陳映雪 北榮陳映雪 ADHD: Delay in Cortex development Shaw et al 2007 (NIMH) 北榮陳映雪 北榮陳映雪 北榮陳映雪 北榮陳映雪 Children with ADHD Demonstrate Delayed Cortical Maturation in Most Areas An exception is in the primary motor cortex where the ADHD group demonstrated earlier cortical maturation Shaw, P. et al. 2007, PNAS. 北榮陳映雪 •nigrostriatal dopamine pathway (from substantia nigra to caudate nucleus) •mesolimbic dopamine pathway ( from ventral tegmentum to frontal cortex) •The dopamine transporter density is more than an order of magnitude higher in the caudate nucleus than the prefrontal cortex , which is the reverse pattern of relative density of the D4 receptors, so the regulation of levels of synaptic dopamine by the reuptake process should differ dramatically in these two brain regions. •the site of action of methylphenidate, which blocks the re-uptake process. 北榮陳映雪 ADHD治療原則 治療目的以改善症狀、學習、行為及 人際關係,並預防日後合併症 治療有其黃金時段 藥物為改善症狀的主要治療 須合併其他治療改善學業、處理情緒 方式及社交技巧 父母需瞭解疾病,並調整管教方式 北榮陳映雪 Treatments for ADHD . Psychotropic medications (> 4 years old) Psychotherapy or psychosocial treatment improve the core symptoms of ADHD in 70% of treated children Behavioral therapy or Cognitive-behavioral therapy Social skill / impulse control skill training Problem solving training Parental training Psychoeducation Other management, but no evidence of effectiveness Sensory intergration perceptual stimulation/training dietary management herbal and homeopathic treatments biofeedback meditation 北榮陳映雪 SNAP Inattention (Teacher) INATTENTION (T) . HYPERKINETIC DISORDER combined medmgt psychosocial community 2.5 2 1.5 1 0.5 D 3M 9M ASSESSMENT POINTS 北榮陳映雪 14M League Table of all Treatments in MTA Study Outcome domains Combined Medication Behavioura l Community Care ADHD symptoms =1 =1 =3 =3 1 2 3 4 =1 =1 3 4 1 2 3 4 1 =2 =2 4 1 2 3 4 Aggression/ ODD Internalisin g Symptoms Social skills Parent-child Relations Academic achievemen t 北榮陳映雪 psychotropic medications 1. CNS stimulants (Short acting & long acting) methylphenidate (MPH), Ritalin, Concerta D-amphetamine Pemoline (hepatic toxicity) 2. Antidepressants TCA (severe CV side effects) SSRI (fluoxetine, sertrazline ……) 3. 4. 5. Atomoxetine Clonidine (for severe aggressive cases, oversedation) Antipsychotics (oversedation) 北榮陳映雪 ADHD Pharmacotherapy – Responsiveness Methylphenidate Amphetamine Pemoline Tricyclic antidepressants Bupropion MAOI Clonidine/ Guanfacine 0 20 40 60 % Responders 80 Wilens TE, Spencer TJ. Presented at Massachusetts General Hospital’s Child and Adolescent Psychopharmacology Meeting, March 10-12, 2000, Boston, MA. 北榮陳映雪 100 Mechanism of Action of Stimulants Presynaptic Neurone Amphetamine blocks vv Storage vesicle Cytoplasmic DA Amphetamine blocks reuptake DA Transporter Synapse Methylphenidate blocks reuptake Wilens T, Spencer TJ. Handbook of Substance Abuse: Neurobehavioral Pharmacology. 1998;501-513. 北榮陳映雪 北榮陳映雪 Pervasive Developmental Disorders 1. 2. 3. 4. Autistic disorder Asperger’s disorder 星 星 的 孩 The Story of Temple Grandin Rett disease PDD NOS Characteristics of Autistic disorder Diagnostic criteria (DSM-IV) Impaired social interaction (quality & quantity) Impaired communication, usually severe Activities, behaviors and interest that are repetitive, Restricted and stereotype. Onset: < age 3 years diagnosis: around age 2-3 years delayed or abnormal function development Male predominant 北榮陳映雪 Autistic disorder : Associated features <1> 75%: retarded level, <2> PIQ>VIQ <3> language expression below language comprehension <4> splinter ability: hyperlexia, (able to read) good at puzzle, date,… <5> odd response to stimuli oversensitive, exaggerated reaction, fascination to stimuli, hypo-sensitive <6> behavioral symptoms: hyperactivity, inattention, aggression, temper tantrum stereotype behaviors, self-injury(head banging, biting), 北榮陳映雪 Autistic disorder Prevalence: 2-5/10,000 , (severe autism) Male predominant Course: life-long Prognosis depends on “language skills” (5y/o) & “overall intellectual level” 1/3: partial independence highest functioning adult : still had symptoms 北榮陳映雪 Asperger’s disorder DSM-IV Diagnostic Criteria A. Qualitative impairment in social interaction, B. Restricted repetitive and stereotyped patterns of behavior, interests, and activities C. No delay in language D. No delay in cognitive development or in the development of age-appropriate self-help skills, adaptive behavior (other than in social interaction), and curiosity about the environment in childhood. F. Function impairment 北榮陳映雪 Comparison of Asperger’s disorder with autistic disorder (I) male > female (both), prevalence: 1-5/1000 (or higher) Age of diagnosis: later, > 5y/o Social and communication deficits are less severe. Normal curiosity about environment No delay in cognitive function, self-help skills, Language development normal lack of empathy problems with pragmatic responses & difficulty with the emotional content of communication problem of integrating affective and social cognitive aspects of a situation. 北榮陳映雪 Comparison of Asperger’s disorder with autistic disorder (II) Difficulties with new environments and changes in their normal routine, but less severe than autism. (rigid & stubborn) Special & circumscribed interest are more prominent e.g. Train, Taiwan history, numerical, …… In autism: Puzzle, date memorized, space, mechanical… VIQ is usually > PIQ (usually reverse in autism) Clumsiness is more frequently seen, but less severe. Outcome is usually more positive in asperger’s. Go to college, get married, held a job, some social relation… family history is more frequently positive 北榮陳映雪 PDDs (ASD) are lifelong disorders 北榮陳映雪 Etiology of Autistic disorder Non-psychogenic Generalized brain dysfunction Neurodevelopment disturbance (< 30weeks pregnancy) seizure: EEG abnormal (25%) PKU, maternal rubella, fragile x syndrome ( 10% autism, mostly males), tuberous sclerosis (1/4 affected are autistic) hyperserotonin Imaging findings: Reduced size of Corpus Callosum, Anterior Cingulate Gyrus , Cerebellum low activity in the parietal areas and the corpus callosum. 北榮陳映雪 北榮陳映雪 北榮陳映雪 Autism and Cerebral Hypoperfusion fMRI Cerebellar Blood Flow and Activation 北榮陳映雪 Allen et al., 2003 Am J Psychiatry 160(2):262-73 Mirror Neuron 鏡像神經元 大腦內建機制 (anterior cingulate cortex) 模仿動作, 看到他人動作,感覺再轉到運動。 生物存活要件之一, 同理心情緒反應上可能扮演重要角色 自閉症可能與此功能受損有關 情緒圖譜理論(salience landscape theory) 杏仁核 (amygdala): 長期處理情緒獲得情緒圖譜,記載 各種情緒意義。 自閉症情緒圖譜嚴重扭曲。 北榮陳映雪 北榮陳映雪 Treatment (for autism & Asperger’s disorder) No specific treatment Behavioral therapy Speech, communication, cognitive & social skill training Educational interventions Individual psychotherapy (for socially handicapped & low esteem) Parent education and training 北榮陳映雪 Therapeutic Programs SI: Sensory Integration/Occupational Therapy ABA : Applied Behavior Analysis PRT : Pivotal Response Training PECS :Picture Exchange Communication System TEACCH: Treatment and Education of Autistic and Communication Handicapped Children Floor time Social Stories Music therapy …………… 北榮陳映雪 自閉症早療重點 (一) 治療情境需高度結構化 (二) 多利用視覺教材輔助語言溝通, 與兒童有興趣事物作聯結 (三) 順應個別需求, 儘量團體人數愈少愈佳 (四) 治療情境, 方式, 及治療師不宜經常變動, 若有,需以漸進方式及小幅變動為宜 (五) 循序漸進, 避免過度強制自閉症兒童 (六) 需有機會與正常兒童互動 (七) 治療需推廣到家庭, 學校, 社區 (八) 目前頗盛行:Portage program 北榮陳映雪 Treatment (for autism & Asperger’s disorder) Medication: can help with symptoms SSRI (stereotype, self-harm beh, depression, anxiety, withdraw), Antipsychotic (impulsive, psychotic) Depakene (mood stablizer, impulsive) Stimulants (for ADHD/ADD) 北榮陳映雪 北榮陳映雪 The Ecology of Adolescent Behavior Treatment Provider Neighborhood School Peer Group Extended Parents Child Siblings Family 北榮陳映雪 Tourette’s disorder Multiple tics disorder Characteristic: • Multiple motor tics (Simple or complex) • Vocal tics ( simple or complex, coprolalia) • Wax & Wine course • Cephalic- caudal pattern, repetitive, • Irresistible but able to be suppressed for some peiords. • A history of motor tics before development of vocal tics. Characteristic of Tourette’s disorder Prevalence:0.05-5.2/10.000 Male>female: 1.5-9 :1 Onset is almost always in childhood (age8-10 years) or adolescence.; Symptoms frequently worsen during adolescence, it is common to persist into adult life 50% remitted during adolescence 北榮陳映雪 Associated Features of Tourette’s disorder Comborbid disorders: ADHD Obsessive-compulsive disorder Depressed Pathophysiology Hypersensitivty of D2, Neuroimaging: basal ganglia (volume reduction?) Autoimmune disease(? post streptoccocal infection) 北榮陳映雪 Treatment of Tics/TS: A. Psychopharmacological management: 1. Antipsychotics 2. Clonidine 3. For case of poor response to antipsychotics SSRI 4. First choice Atypical antipsychotics For case of combination with OCD Combing antipsychotics with CNS stimulant For comorbid ADHD if indicated. B. Psychoeducation & Psychological support C. Parental/teacher psychoeducation 北榮陳映雪 Mental Retardation Diagnosis (Both IQ & adaptive function) Mild ( FIQ < 70, educable, grade 3 or 4), Moderate (FIQ < 50/45 trainable), Severe (FIQ < 35) Profound (FIQ<20) early intervention 北榮陳映雪 Mental retardation Special education & training Strength & weakness Practical, individualized Living skills, self help skills, Social Family attitude & Guidance (Co-therapist) MR & other psychiatric disorders Increase prevalence of psychiatric disorders Biological, psychological & social factors Principle of Rx as other psychiatric disorder (drugs:start low, go slow) 北榮陳映雪 北榮陳映雪