Transcript Reading disorder (dyslexia)

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
 Endency o choose immediae 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
北榮陳映雪
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
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
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
ADHD: Delay in Cortex development
Shaw et al 2007 (NIMH)
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
CNS stimulants
In Taiwan: Methylphenidate (MPH)
Ritalin : Short acting (duration: 3-5 hours)
bid (morning & noon) or tid.
Dosage: 0.3-1.0mg/kg/day. (1# :10mg)
Concerta (OROS) : long-acting
once a day (duration: 12hours)
improve compliance (87.3%
Stable blood level
Dosage: 1-2 mg/kg/ day (1# : 18, 36, 54mg)
Disadvantage: high cost

87.3% of 400 adolescents & adults satisfied within 3 months of
study.
北榮陳映雪
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
Effect of MPH on WM Brain Activation:
Narrows the Focus
med
frontal
gyrus
MPH may enhance
performance by
improving PFC’s
ability to filter out
distracters.
thalamus
Schweitzer et al, 2004
北榮陳映雪
mid frontal
gyrus
precentral
gyrus
CNS stimulants : side effects
Appetite loss (1/3, nutrition, drug holiday)
Sleep disturbance (avoid MPH after 6:00pm)
Tics ( predisposing, reduce dose, or add antipsychotics,
clonidine)
Rebound phenomenon (posttherapeutic agitation, anger,
lethargy (increase dose)
Depression, irritability (rare, change to other drug)
Hallucination, psychosis (rare, reduce dose)
Other considerations:
Growth: <1 cm in height with 2 years
Drug abuse: no increase incidence in treatment.
(The increased risk of substance abuse in untreated ADHD subjects
has profound implications for parents, teens, and society.)
北榮陳映雪
北榮陳映雪
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