童綜合醫院心身科主治醫師 國立陽明大學神經科學研究所暨中研院生醫所分子神經醫學博士候選人 台灣成癮科學學會理事 黃尚堅 青少年常見精神疾病介紹 --深入淺出 童綜合醫院心身科主治醫師 國立陽明大學神經科學研究所暨中研院生醫所分子神經醫學博士候選人 台灣成癮科學學會理事 黃尚堅

大綱 憂鬱症 精神分裂症 注意力不足/過動症 成癮疾患

Suicide (prevalence) Mood disorders: lifetime risk of commit suicide 15% Risk of attempted suicide 41-fold in depressive disorder Suicide attempt: F > M, completed suicide: M > F Risk of completed suicide Male: substance abuse, Female: < age 18 responsibility for kids

憂鬱症之診斷標準 一、情緒：1)情緒低落(depression) 2)對任何事情 均沒樂趣(anhedonia) 3)人生乏味有自殺傾向 二、認知：4)自責愧疚 5)記憶力、注意力下降， 無法下決定 三、行為：6)整天不想動或是焦躁不安 7)疲倦乏力 四、身體：8)胃口或體重下降或上升 9)失眠或多眠

臨床憂鬱症之多型性型態 憂鬱症 重鬱症 單極性 憂鬱症 慢性 輕鬱症 雙極性 憂鬱症 憂鬱性 精神病 女性相關 憂鬱症 內科疾病 相關憂鬱症 精神疾病 共病憂鬱症 憂鬱性格 器質性 憂鬱症

Major depressive episode (1) Occur in both major depression and bipolar disorder Severity (mild, moderate and severe) without or with psychotic features DSM-IV criteria: More than 5 symptoms Duration > 2 weeks Significant impairment in functioning Not related to medical illness, medications or substance abuse Not accounted by bereavement (loss < 3 months)

Major depressive episode (2) Psychotic depression Delusions and hallucinations (common:mood – congruent, Uncommon: mood - incongruent ) Melancholia Loss of pleasure, early morning awakening, diurnal variation, wt loss, severe guilt and agitation/retardation Seasonal affective disorder (winter depression) Hypersomnia, carbohydrate craving, overeating, weight gain and fatigue

Comorbidity of affective disorders Phobia, Panic disorder, Medical illness OCD 30 – 70% Affective disorders 30 – 40% Personality disorder 30 – 70% Substance abuse Schizophrenia 50 – 60% 25 – 50%

Differential diagnosis Adjustment disorder with depressive mood Uncomplicated bereavement Organic or psychoactive substance-induced mood disorders Schizoaffective disorders or Schizophrenia(delusion or hallucination > 2wks without mood symptoms) Dementia Secondary depression

The neurotransmitter pathway Dysregulation of Serotonin (5HT) and Norepinephrine (NE) in the brain are strongly associated with depression Dysregulation of 5HT&NE in the spinal cord may explain an increased pain perception among depressed patients1-3 Imbalances of 5HT&NE may explain the presence of both emotional and physical symptoms of depression. Descending Pathway Descending Pathway Ascending Pathway Ascending Pathway Stahl SM. J. Clin Psych. 2002;63:203-220. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.

Symptoms of Depression 不同神經傳導物質引發不同憂鬱症狀 SEROTONERGIC NORADRENERGIC (血清素) (正腎上腺素) Decreased concentration Retardation Loss of energy Low motivation Reduced self-care Lassitude Tiredness Agitation Loss of appetite Decreased libido Suicidal ideation Aggressive behavior Irritability Depressed mood Loss of pleasure Insomnia or hypersomnia Feeling of worthlessness Anxiety Pessimism Decreased concentration Retardation Loss of energy Low motivation Reduced self-care Lassitude Tiredness Depressed mood Loss of pleasure Insomnia or hypersomnia Feeling of worthlessness Anxiety Pessimism overlap of 5H-T & NA function Healy , Van Praag , Montgomery

病因：多面向與複雜性 生物因素：賀爾蒙及腦生化變化 基因因素：家族憂鬱危險因子 環境因素：生活事件(家人死亡、離婚、失業、生病與搬家)

Heritability Concordance rate of Monozygotic twin (MZ) is significantly higher than that of Dizygotic twin (DZ) Heritability of Major depression is about 0.4 (Height and IQ >0.95, Schizophrenia 0.8, Bipolar disorder 0.6)

生活壓力事件與5-HT1A promotor 多型性基因型態之相互影響憂鬱症 Probability of MDE Number stressful life events Caspi A, et al. SCIENCE 301; 386, JULY 18, 2003

Major depressive disorder: therapy Psychotherapy: mild depression supportive, brief psychodynamic , interpersonal psychotherapy (IPT) and cognitive therapy (CT), cognitive-behavior therapy (CBT), guidance and counseling Antidepressant drug therapy Acute therapy- at least 6-9 months Maintanence therapy: more than 1-2 years (full dose, more protective against recurrence) Light therapy: mild seasonal depression Exercise: mild depression

Apoptosis

Generation of depression in the context of biopsychosocial status across lifetime Environmental stress Vulnerability Lifetime Hormonal Immune Brain degeneration Medical Psychiatric Sleep Genetic Family Hx Depression Alcohol/drug Psychosocial risk F

憂鬱症之神經學病因 Dystunction of multiple brain regions contributes depression −Hippocampus(海馬迴): learning and memory (cognition), feedback regulation of HPA axis function (endocrine) −Chronic stress decrease BDNF− atrophy of hippocampal neurons −Frontal cortex(額葉皮質): short-term memory, ruminative ideation, impulsivity −Amygdala(杏仁核): emotional response to psychological stimuli −Dopaminergic brain reward(獎賞) regions (N. Accumbens伏擊核)

(活化) (憂鬱症) 功能性腦造影-Tc99

(神經再生區域主要在海馬迴)

Antidepressant Treatment May Normalize BDNF Levels (抗憂鬱劑可增加腦神經滋養因子) BDNF Levels in Humans After 8 Weeks of Antidepressant Treatment1 Regulation of BDNF Expression in Rats by Antidepressant Pre-Treatment2 50.00 P<0.001* 40.00 BDNF (ng/dl) 30.00 20.00 KEY POINTS Antidepressant treatment may help regulate BDNF levels. Antidepressant treatment may significantly increase neurogenesis in the adult hippocampus.1,2 The up-regulation of neurogenesis was observed with chronic, but not acute, administration of different classes of antidepressants and electroconvulsive therapy, indicating that neurogenesis may be a common target of antidepressant medications. Antidepressant treatment may normalize BDNF levels. A study of depressed patients, illustrated here at left, showed an increase in patient BDNF levels following treatment. BDNF levels were shown to be higher for depressed patients following eight weeks of treatment.3 Stress decreases and antidepressant treatments increase the expression of BDNF in the hippocampus4: At right, darker staining suggests higher BDNF levels in the hippocampi of rats following treatment. BACKGROUND The Gonul study compared serum-derived BDNF (sBDNF) of depressed patients (n=28) with those of controls (n=18) before and after eight weeks of treatment. Severity of and response to depression were measured by the Hamilton Rating Scale for Depression (HAM-D17).3 Baseline sBDNF levels were significantly lower than those of controls (P=.0015). After eight weeks, sBDNF levels of patients had increased significantly (P<.001) and no longer differed from controls. One study showed that pretreatment with antidepressants blocked the down-regulation of BDNF in response to stress in the hippocampus.4,5 The influence of acute restraint stress (90 minutes) or long-term antidepressant treatment (21 days) on levels of BDNF mRNA were determined by in situ hybridization analysis.4,5 Abbreviations: CA1 = CA1 pyramidal cell layer; CA3 = CA3 pyramidal cell layer; DG = dentate gyrus granule cell layer.4 REFERENCES Malberg J, Eisch AJ, Nestler EJ, et al. Chronic antidepressant treatment increases neurogenesis in adult hippocampus. J Neurosci. 2000;20:9104–9110. Duman R. Depression: A case of neuronal life and death? Biol Psychiatry. 2004:56:140-145. Gonul AS, Akdeniz F, Taneli F, et al. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci. 2005;255:381-386. Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54:597-606. Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995;15:7539-7547. 10.00 Control Antidepressant Following treatment, higher levels of BDNF (indicated by staining) appear in prominent hippocampal regions (CA1, CA3, DG) Baseline Endpoint (n=28) Control (n=18) * Difference between baseline and follow-up in treated samples 1. Gonul AS, et al. Eur Arch Psychiatry Clin Neurosci. 2005;255:381-386. Reprinted with permission from Springer. 2. Duman RS, et al. Arch Gen Psychiatry. 1997;54:597-606. Reprinted with permission from the AMA. 24

Recurrence Becomes More Likely With Each Episode of Depression First episode1-3 >50% Second episode2 ≈70% Third+ episode2 ≈ 85% 0 20 40 60 80 100 Recurrence risk (%) following recovery during long-term follow-up* *Patients were followed for 3 to 15 years after recovery from previous episode. Judd LL, et al. Am J Psychiatry. 2000;157:1501-1504. Mueller TI, et al. Am J Psychiatry. 1999;156:1000-1006. Keller MB, Boland RJ. Biol Psychiatry. 1998;44:348-360.

大綱 憂鬱症 精神分裂症 注意力不足/過動症 成癮疾患

Schizophrenia ? 精神分裂症? 思覺失調症? 多巴胺過多症? 調絃病?

Social/Occupational Functioning 精神分裂症涵蓋範圍 負性症狀改善 正性症狀改善 Social/Occupational Functioning Long-term care Positive Symptoms Delusions Hallucinations Disorganized speech Catatonia Cognitive Deficits Attention Memory Executive functions (e.g., abstraction) Negative Symptoms Affective flattening Alogia Avolition Anhedonia Social withdrawal Comorbid Conditions Mood Substance use disorder Anxiety Aggression 共病現象 認知功能改善

遺傳模式(80%) 精神分裂症基因的遺傳模式偏向oligogenic model, 可能由幾個到幾十個基因透過彼 此交互作用,每個基因 可能是小到中等程 度effect (genotype relative risk=1.2-2.0)

Perceiving is believing To explaining the positive symptoms of schizophrenia

Nature 1995. 378:176-185

PET during Visual and Auditory Verbal Hallucination Nature 1995. 378:176-185

ADHD Schizophrenia 叛逆期 ……… 多巴胺系統約20-25歲間完成 ADHD Schizophrenia 叛逆期 ………

Gene-Environment interactions COMT genotype alone had no predictive effect on the emergence of schizophrenic illness by age 25, but in combination with early marijuana use, the risk odds ratio for val/val genotype was ten-fold greater than in the general population.

Rate of Grey Matter Loss in Schizophrenia

大綱 憂鬱症 精神分裂症 注意力不足/過動症 成癮疾患

注意力不足/過動症的定義 屬於發展的疾患 (a developmental disorder) 屬於神經內分泌影響所導致的行為疾患( is a neurobehavior disorder) 在生命早期就開始出現(Stars early in life) 症狀的表現是慢性且持續的(A chronic persisting course of symptoms) 功能的影響並不是暫時的(Impairment is not temporary) Gadow&Weiss,2001, WillensBiederman&Spencer,2002 American Academy of Pediatrics, 2000

注意力不足過動症的發生率 因文化而不同 台灣本土的研究顯示盛行率為7.5% (Gau SS, Am J Psychiatry 2005;162:1344-50) 學齡期兒童的好發率 3% -10% , 男生：女生 = 3-4：1 30%-50%症狀持續至青少年或成人 (症狀的表現情形可能會改變) (Wender,1995,Wilens,Biederman&Spencer,2002) 約1/2 ADHD患者的小孩也罹患ADHD 約10%-35% ADHD病童之一等親患有ADHD

注意力不足過動症的成因 病因並不明確→多種成因交互作用導致部分大腦病變 和基因遺傳有關的腦部發展的疾病(70%-80%) 多巴胺攜帶基因（dopamine transporter gene, DAT1 10-repeat allele） 多巴胺 D4(DRD4 7-repeat allele), D5, D1受體基因 Taq 1 polymorphism of the dopamine beta hydroxylase gene SNAP-25 gene 環境影響(20%-30%) 懷孕中喝酒抽煙使用藥物、及週產期併發症 胎兒時期，大腦管理注意力及動作部位發育異常 有毒物質 發育過程損傷 受傷 基因與環境彼此相互影響的結果 症狀持續或是保護減少症狀的因子:在家庭中以及在學校中與其他人關係的品質(quality of relationships within the family and at school)

ADHD是生理上的疾病必需接受治療! 造成ADHD的主要問題來自腦部額葉的功能異常 ADHD的患者葡萄糖代謝活性明顯降低 　（白、紅及橘色區域表示活性較高） 注意力不足過動症ＡＤＨＤ是一種生理上的疾病，必須接受治療！ 造成ADHD 的問題主要來自腦部額葉的功能異常 從PET( Positron Emission Tomography)掃描中發現，一般成人的大腦（左）與患有ADHD卻未治療的病患大腦（右）不同。ADHD病患的葡萄糖代謝活性明顯比較低。   American Academy of Clinical and Adolescent Psychiatry Official Action. J Am Acad Child Adolese Psychiatry

注意力不足 做作業、工作及活動時，無法注意細節或經常粗心犯錯 工作或遊戲時經常有困難維持注意力 不專心聽別人對他說話 不能將指示的事做完 經常有困難規劃工作及活動 排斥需全神貫注的事情（寫作業） 經常遺失必備的物品（玩具、鉛筆、書） 經常容易受外界刺激影響而分心 日常活動經常遺忘事情

認識 ADHD過動型/衝動型 不花時間修改作業 知道規則及後果，但仍重複犯錯 容易被激怒 因為無法“先停下來想想”而惹麻煩 喜怒無常 不等候指示就開始工作 匆促完成工作 (特別是無聊的工作) 不花時間修改作業 容易被激怒 喜怒無常 容易沮喪 容易失去控制 不易接受變化 社會技巧不成熟 無法為長期目標或報酬而努力 這些行為開始影響在學校或家裡的正常機能時， 才可能懷疑罹患 ADHD ! Rief S. The ADD/ADHD Checklist, 1998

注意力不足/過動症 注意力不足/過動-衝動症狀6項或6項以上 症狀達六個月且已達適應不良 7 歲以前出現有些損害性的症狀 在兩種以上的場合造成損害（學校、家中） 有明確證據顯示社會、學業及職業功能有重大損害 無法以廣泛性發展障礙（例如自閉症）、情感性疾患、焦慮症等解釋 分三個類型：混合型；注意力不足型；過動/易衝動型

注意力不足過動症的症狀分類 注意力不足 注意力不足型 過動 混合型 過動/衝動型 衝動

American Academy of Pediatrics Vol.105 No.5 May 2000 建議 除了使用精神科會談問診、蒐集疾病史資料、運用臨床診斷準則以及相關量表外，下列的檢查並不建議作為診斷評估之常規檢查工具(other diagnostic tests are not routinely indicated to establish the diagnosis of ADHD) 血中鉛的濃度(Blood lead levels): lead encephalopathy very few have elevated lead levels at school age 甲狀腺功能檢查No significant associations between abnormal thyroid hormone levels and ADHD 腦部攝影檢查以及腦波檢查(Brain imaging studies and electroencephalography do not show reliable differences between children with ADHD and controls) Due to lack of consistent findings→current report not support routine use EEG in the diagnosis of ADHD 多向度注意力測驗Continuous performance tests (low odds ratios): not support

注意力不足過動症為什麼需要接受治療？ 家庭生活 其父母離異或分居的情形 是一般人的3-5 倍2-3 手足發生肢體衝突的情形 是一般人的2-4倍4 就學情況 學習成就低 學習障礙、情緒障礙 46% 被學校退學1 35% 自動辦理退學1 社會適應力 有40%ADHD男性在16歲 以前被以重大罪行起訴5 52%有酒精或毒品濫用現象5 少年監獄中有70%是ADHD患者5 無法克制消費慾望 工作情況 持續換工作、無法遵守指令 由於其行為及社會適應不良 平均每年損失USD10,0006 1. Barkley, et al., 1990. 2. Barkley, Fischer et al., 1991. 3. Brown & Pacini, 1989 4. Mash & Johnston, 1983. 5. Why attention deficit disorder on a legal page, 6. NHTSA 2005.

ADHD ADHD容易合併其他疾病 ADHD Alone 31% 單純只有ADHD ODD 40% 反抗對立 11% Tic 抽動 14% The MTA study shows that up to 69% of children with ADHD have one or more coexisting conditions (including major depression, conduct disorder, oppositional defiant disorder, Tourette’s syndrome, and learning disabilities), these conditions may complicate a diagnosis of ADHD1. The primary care physician may more easily identify and target these other conditions, thereby missing the ADHD diagnosis. Current medications for ADHD may exacerbate comorbid conditions A note about the MTA study sample and potential sample bias: “In the MTA study, the investigators set out to enlist a very heterogeneous sample: they “actively recruited girls,” sought out children with “disparate comorbid diagnoses,” and attempted to include “children and families either currently receiving treatment or who are amenable to intervention”.2 The latter decision took sample recruitment beyond clinic referrals into the general population, where advertisements, word of mouth, and other methods were used to stimulate self-referral. On one level, the enlistment strategies developed in the MTA study appear to be very inclusive: all children with ADHD, irrespective of clinic status, would be eligible for study. The limiting factor behind this strategy is the lack of control over the factors determining self-selection. These factors or sample filters condition the identification and take-up of subjects and come in 2 forms: referral filters, which control the movement of the subject pool toward the site, and study filters, which control the enlistment and retention of study subjects.”3 Another limitation regarding this study was the sample group was restricted to the Combined type of ADHD. Inattentive type has a different comorbidity profile than combined type. Jensen P, et al. Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 1999;56:1073-1096. 2. Hinshaw SP, March JS, Abikoff H, Arnold LE, Cantwell DP, Conners CK, and others. Comprehensive assessment of childhood attention-deficit hyperactivity disorder in the context of a multisite, multimodal clinical trial. Journal of Attention Disorders 1997;1:217–34. 3. Boyle MH, Jadad AR. Lessons from large trials: the MTA study as a model for evaluating the treatment of childhood psychiaric disorder. Can J Psychiatry 1999;44:991–8. Conduct 品行疾患 38% Anxiety/mood 焦慮憂鬱 Jensen P, et al, Archives of General Psychiatry, MTA study; 1999;56:1073-1096

共病症 注意力不足過動症是高度共病症的疾患 共病症是指在一個個案身上同時具有兩個疾病診斷 共病症的評估診斷以及治療非常重要 共病症的治療和注意力不足過動症的治療並不同，是各自獨立的 共病症的出現可能影響疾病的預後(Co-morbidity may affect prognosis) Studies of children with attention deficit hyperactivity disorder (ADHD) consistently document high rates of co-morbid psychiatric conditions, including conduct disorders, anxiety disorders, depression and other mood disorders, to name a few1,2. Co-morbidity is defined as two different diagnoses present in an individual patient. It is important to recognize co-morbid disorders. Co-morbidities may require treatment independent from and additional to therapy for ADHD. 1. Brown TE. Attention deficit disorders on co-morbidities in children, adolescents and adults. Washington DC: American Psychiatric Press Inc, 2000. 2. Barkley RA. Attention-Deficit Hyperactivity Disorder. A Handbook for Diagnosis and Treatment. New York: Guilford Press, 1988.

多元化治療模式研究(MTA) Multimodal Treatment Study of Children with ADHD 由美國國家精神衛生研究院和教育部共同主持的大型中立研究。 目的為確認行為治療以及藥物治療的效果， 是否一定要用藥？行為治療是否有用？ 長達14個月，多中心，分成四組比較。 受試者共579人 1992年, 由美國國家精神衛生研究院和教育部共同舉辦的一個中立的大型試驗- MTA Study, 企圖去釐清這個爭議. MTA Study 長達14個月，多中心，將579病童隨機分為四組,一組為密集的行為治療組；一組為一天使用12小時MPH的單用藥物治療組; 一組為藥物、行為合併治療組; 最後回歸一般的情境的例行性社區照護組，其平均的用藥時間為一天8小時 單用密集行為治療組 145人 單用藥物 治療組 (Tid-12hrs) 145人 單用藥物 治療組 145 藥物、行為 合併治療組 145人 145 藥物、行為 合併治療組 145 例行性 社區照護組 (Bid-8hrs) 144人

多元化治療模式研究(MTA) Multimodal Treatment Study of Children with ADHD 發現 X 例行性社區照護 單用密集行為治療 單用藥物治療 ◆ 合併治療 過動衝動症狀 焦慮、憂鬱症狀 合併療法及單用 藥物治療效果最佳 合併療法及單用 藥物治療效最能改善 焦慮、憂鬱症狀 整體社交技巧 親子衝突 MTA Study 發現在核心症狀－過動衝動或因核心症狀直接引起的情緒問題，如焦慮和憂鬱症狀，合併和單用藥物療法的效果最好。 在人際互動部分，如社交技巧及親子衝突，加入行為治療的合併療法則效果最佳 合併療法最能提升 孩童整體社交技巧 合併療法最能 降低親子衝突

神經化學 病理生理學 (Neurochemical Pathophysiology of ADHD) 藉由 1)阻斷多巴胺及正腎上腺素被再吸收 2)增加神經末梢結節釋放多巴胺和正腎上腺素 　　　提高神經突觸前多巴胺和正腎上腺素的量 　　　　　　　　　　　　　　　　　　　(Wilens & Spencer, 2000)

治療ADHD的第一線用藥: Methylphenidate (MPH) 使用超過50年, 證實長期治療的安全性 建議 stimulants為第一線治療選擇。 The American Academy of Pediatrics (American Academy of Pediatrics, 2001), an international consensus statement (Kutcher et al., 2004), and the Texas Children’s Medication Project (Pliszka et al., 2006a) , Journal of American Academy of Child and Adolescent Psychiatry 2007, NICE, SIGN and European guidelines 美國的AAP及AACAP, 英國的NICE及歐洲大陸使用的European guidelines 均支持MPH為第一線用藥並建議須包含在治療計劃中 附註: AAP(American Academy of Pediatrics)及AACAP(American Academy of Child and Adolescent Psychiatry)和英國的NICE American Academy of Clinical and Adolescent Psychiatry Official Action. J Am Acad Child Adolesc Psychiatry 2002; 41 (Suppl 2); 26S–49S Journal of American Academy of Child and Adolescent Psychiatry, 46:7, JULY 2007

注意力不足過動症之用藥 第一線用藥：methylphanidate中樞神經活化劑 何時停藥：drug holiday、個別性考量 作用：影響腦前額業多巴胺和正腎上腺素之分泌 對50%-95%的過動兒有效 利他能(Ritalin:10mg/tab) ：0.3-1.0mg/kg/day 、藥效4-6小時 專思達(Concerta: 18mg/tab, 36mg/tab) ：原則上18mg/day=15kg-20kg, 36mg/day=28kg-40kg 、藥效12小時 副作用：食慾減退、體重下降、失眠、頭痛、胃腸不適、異質性反應 用藥原則：最低的副作用以及最低的有效劑量 何時停藥：drug holiday、個別性考量

ADHD 治療藥物的反應率 Methylphenidate Amphetamine Pemoline Tricyclic antidepressants Bupropion MAOI 為什麼把Stimulant放在第一線呢, 從這個Wilens 2000發表的藥物反應率比較圖可以看出, 有80%的患者對Stimulant 有反應, 而第二線的Antidepressants, 其反應率只有50%-60%. Clonidine/ Guanfacine 20 40 60 80 100 % Responders Wilens TE, Spencer TJ. Presented at Massachusetts General Hospital’s Child and Adolescent Psychopharmacology Meeting, March 10-12, 2000, Boston, MA.

改善社交技巧→改善人際互動關係 減少對立反抗/攻擊行為→改善關係 藥物合併行為治療對整體功能改善的效果較佳 行為治療可以協助什麼？ (個別化考量) 改善社交技巧→改善人際互動關係 減少對立反抗/攻擊行為→改善關係 藥物合併行為治療對整體功能改善的效果較佳

注意力易分散的孩子 不同種類的刺激分散度不同 觀察孩子容易受到何種外界刺激干擾而改變正在進行的活動→調整環境 分散度高的孩子容易因新事務而分心，不利學習→調整環境、分段學習 對策：學習環境應佈置簡單、安靜、主題明顯、適度應用分段學習以及獎勵

認知行為治療 注意力訓練 增強對時間的掌握：鬧鐘 以視覺化的訊息協助自我提醒然後逐漸養成習慣：貼紙條 訓練對計劃的規劃以及執行力：整理書包的步驟 藉由討論、練習增進對周圍環境的覺察 討論過去事件找出或學習替代行為、或預防再次發生的方式增進對自我的覺察

社交技巧訓練(同理心的加強) 在家庭中的練習 學校中的練習 醫院或其他機構 年齡相當的小團體 由活動中學習合作、輪流等待、服從、角色扮演、別人對自己行為的回饋

對學校教育的協助 協助老師對此疾病有正確的認識 避免予以標籤化或對個案有負向情緒 協助老師了解藥物使用的目的以及可能的副作用 規則能以外顯的方式列出(海報、白板) 協助訂定行為約定並執行 讓老師成為治療的協助者

生活對策 在美國國衛院(NIMH)為過動症者所編的小冊子裡條列了一些方法可以幫助過動者在工作或學校能有比較好的表現： 如果需要的話，把別人的要求問清楚－不要去猜別人期望你做什麼。 把大型的，複雜的工作，分割成幾個小部分來完成。為每一項作業設定最後完成的期限，當你完成每一樣工作獎勵你自己。 每天都列出「當日工作清單」。 在安靜的地方工作。一次只做一件事。讓自己稍稍休息一下。 利用日誌幫助自己的工作進度上軌道。 創造出生活的規律性。每天以一樣的順序做相同的事。 飲食要均衡，適當的運動，每晚讓自己有充足的睡眠。

大綱 憂鬱症 精神分裂症 注意力不足/過動症 成癮疾患

Addiction: It’s a Brain Disease ! (成癮是一種腦部疾病)

Addiction Medical Medical DRUGS Economic Social Neurotoxicity AIDS CANCER MENTAL ILLNESS Neurotoxicity AIDS, Cancer Mental illness DRUGS The effects of drug abuse are wide ranging and affect people of all ages. Besides addiction, drug abuse is linked to a variety of health problems, including HIV/AIDS, cancer, heart disease and many more. It is costly to individuals and society, and is linked to homelessness, crime, and violence. Social Economic Health care Productivity Accidents Homelessness Crime Violence

Your Brain on Drugs Today 1-2 Min 3-4 5-6 6-7 7-8 8-9 9-10 10-20 20-30 YELLOW shows places in brain where cocaine goes (striatum) Front of Brain Back of Brain We can now measure the brain’s response to drugs of abuse in real time. This slide shows images of a human brain taken at different intervals following administration of radioactive cocaine. Because the drug was radiolabeled, scientists can see precisely where cocaine binds (yellow signal) and for how long. Such studies teach scientists more about how cocaine exerts its devastating effects. Fowler et al., Synapse, 1989.

Common Myths About Drug Abuse… Drug abuse equates to drug addiction Alcohol is not a drug Addiction is a moral weakness Drug abuse is more common among minorities

Addiction is …. A brain disease Their brains are different from non-addicts’ brains A chronic relapse disease Not just brain disease but also environment cue Initially voluntary behavior Subsequently compulsive behavior A public health problem

Why Do People Take Drugs in The First Place? To feel good To have novel: feelings sensations experiences AND to share them To feel better To lessen: anxiety worries fears depression hopelessness Research has shown that people generally take drugs to either feel good (sensation seekers, or anyone wanting to experiment with feeling high or feeling different) or to feel better (self-medicators, or individuals who take drugs in an attempt to cope with difficult problems or situations, including stress, trauma, and symptoms of mental disorders).

Why do some people become addicted while others do not? Vulnerability (脆弱性) Why do some people become addicted while others do not? What makes some people more vulnerable to drug addiction? Many people try drugs without getting addicted, while others do become addictedsome quickly and easily.

Big Genetic Contribution to Drug Abuse and Addiction… We Know There’s a Big Genetic Contribution to Drug Abuse and Addiction… ….Overlapping with Environmental Influences that Help Make Addiction a Complex Disease.

Biology/genes Environment Biology/ Environment Interactions It is clear today that addiction is the result of complex interactions not only among many genes but also between genes and a host of environmental factors.

Two of the brain-signaling pathways targeted by drugs of abuse transmit dopamine and serotonin: Dopamine and serotonin are chemicals (also known as neurotransmitters) that are normally involved in communication between neurons in the brain. Abused substances can influence functions modulated by either or both of these chemicals. Dopamine is found in numerous brain areas (blue) related to pleasure, motivation, motor function, and saliency of stimuli or events. Serotonin, (red) plays a role in learning, memory, sleep, and mood.

Circuits Involved In Drug Abuse and Addiction All of these must be considered in developing strategies to effectively treat addiction Brain circuits are affected by drug abuse and addiction. The areas depicted contain the circuits that underlie feelings of reward, learning and memory, motivation and drive, and inhibitory control. Each of these brain areas and the behaviors they control must be considered when developing strategies to treat drug addiction. PFC – prefrontal cortex; ACG – anterior cingulate gyrus; OFC – orbitofrontal cortex; SCC – subcallosal cortex; NAcc – nucleus accumbens; VP – ventral pallidum; Hipp – hippocampus; Amyg – amygdala

Natural Rewards Elevate Dopamine Levels DA Concentration (% Baseline) FOOD SEX 200 200 NAc shell 150 150 DA Concentration (% Baseline) 100 100 15 5 10 Copulation Frequency % of Basal DA Output Empty 50 Box Feeding Natural rewards increase dopamine neurotransmission. For example, eating something that you enjoy or engaging in sexual behavior can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals, its increase shown in response to food or sex cues. This basic mechanism has been carefully shaped and calibrated by evolution to reward normal activities critical for survival. 60 120 180 Female Present Time (min) 1 2 3 4 5 6 7 8 Sample Number Mounts Intromissions Ejaculations Di Chiara et al., Neuroscience, 1999. Fiorino and Phillips, J. Neuroscience, 1997.

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