Emotion Functions: Mood Disorders 四川大学华西医院康复医学科 郭华

Mood (Affective) Disorders Roller coaster Quiet river

Group of disorders involving severe and enduring disturbances in emotion (mood)

世界名画家蒙克名作《呐喊》是精神的焦虑以图式显现的最杰出的代表. 在他日记里，曾记下那激动人心的一幕： 尼斯，1892年1月22日， 我和两个朋友还在散步 太阳已快下山了 天空突然间变得血一样红 我似乎感受到了一种悲伤忧郁的气息 我止住了脚步，轻轻地倚在篱笆边 极度的疲倦已使我快要窒息了 火焰般的云彩像血，又像一把把利剑笼罩着蓝黑色的挪威和城镇 我的朋友，他继续独自地走着，而我却呆呆地站在那儿 焦虑使我不停地发抖 我感到四周似乎被一声巨大而又不断的尖叫声震得摇摇晃晃

Outline Concepts The classification Causes of mood disorders Treatment of mood disorders Suicide

Concepts Mood disorders Group of disorders involving severe and enduring disturbances in emotion (mood) (prevalence in population between 8% and 19%)

Concepts Major depressive episode Extremely depressed mood state that lasts at least 2 weeks and includes cognitive symptoms(worthlessness, indecisiveness) and physical symptoms (altered sleeping pattern, changes in appetite and weight, loss of energy)

Concepts Mania Episode of joy and euphoria marked by individual’s extreme pleasure in every activity, hyperactivity, little sleep

Concepts Hypomania less severe version of a manic episode that does not cause marked impairment in social or occupational functioning Dysphoric manic or mixed episode the individual experiences both elation and depression or anxiety at the same time

Concepts Unipolar mood disorder Individuals experience either depression or mania but not both Bipolar mood disorder Individuals alternate between depression and mania

The classification of Mood Disorders Mood (Affective) Disorders Manic episode With or Without psychiatric syrnptoims (mania) Depression (unipolar) Single episode Recurrent episode Bipolar disorders Bipolar-Ⅰ (with maina) Bipolar-Ⅱ (with hypomania) Mixed type Rapid-cycling bipolar disorder Dysthymia Cyclothymia disorder

心境障碍与精神病性障碍的交叉重叠 精神病性障碍 双相障碍 抑郁症 伴精神病性症状的抑郁症 双相抑郁症 难治性抑郁症 Key Point: There is considerable symptomatic and syndromic overlap between different mood and psychotic disorders. Psychosis can be a manifestation of psychotic disorders (such as schizophrenia or schizophreniform disorder), associated with mood disorders, dementia, delirium and substance-induced disorders. Depression occurs in the course of bipolar disorder, but the majority of depression is unipolar. Depression may be resistant to treatment and some cases of treatment-resistant depression may be bipolar depression that has been misdiagnosed as unipolar. Therefore, it is important to understand the epidemiology and presentation of bipolar disorder and to screen for it. 抑郁症 难治性抑郁症 13

反应迟钝，情绪低落，自杀倾向，悲观厌世, 入睡困难，注意力不集中，食欲性、欲降低。

合并精神分裂症、药物成瘾、焦虑或帕金森等 激素问题、头外伤、脑肿瘤或其他疾病。 合并精神分裂症、药物成瘾、焦虑或帕金森等

1.家系研究：2.双生子研究：3.寄养子研究

Look, Holmes's two period?

Vivien Leigh (1913－1967)

Causes of mood disorders

Causes of mood disorders

Causes of mood disorders biological factors if one twin presents with a mood disorder, an identical twin is approximately three times more likely than a fraternal twin to have a mood disorder (heritability approx. 40% for women) psychological factors

Causes of mood disorders stressful life events, hopelessness, negative cognitive styles - overgeneralization social and cultural factors marital dissatisfaction 70% of people suffering with major depressive disorder or dysthymia are women

5-HT NE 焦虑易激惹 焦虑易激惹 焦虑易激惹 焦虑易激惹 焦虑易激惹 精力兴趣 精力兴趣 精力兴趣 精力兴趣 精力兴趣 强 迫 强 迫 性 食欲 攻击 性 食欲 攻击 性 食欲 攻击 动机 内驱力 Stahl SM. In: Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. Cambridge, UK: Cambridge University Press; 2000:135-197.

中枢神经系统5-HT和NE的神经通路 5-HT和NE的神经通路调节不 同的功能 递减脊髓传导的调节疼痛的 反应 这些通路的异常可引起抑郁 的情绪和躯体症状 Dorsal raphe nuclei Caudal raphe nuclei Lateral tegmental NA cell system Locus ceruleus NE 抑郁情绪 自杀观念 睡眠障碍 食欲改变/ 兴趣缺失 关节,淋巴结,背部,腹部的不名区的疼痛 头痛 消化道不适 疼痛反应的调节效应 5-HT – Key Point Emotional and physical symptoms may be the major mediating morbid event leading a patient to seek treatment Background Serotonin (5-HT) and norepinephrine (NE) are secreted in response to physical and psychological stressors Central nervous system (CNS) serotonergic pathways incorporate serotonergic neurons with cell bodies in the upper pons and the midbrain—specifically, the median and dorsal raphe nuclei, caudal locus ceruleus, area postrema, and interpeduncular area The largest loci of noradrenergic neurons is the locus ceruleus in the pons; projections of the noradrenergic system reach many areas in the forebrain and the cerebellum Serotonergic and noradrenergic pathways in the brain modulate various brain functions including mood, sleep, cognition, temperature regulation, appetite, and sexual behavior Descending pathways of the serotonergic and noradrenergic systems in the brain stem project down the spinal cord and modulate sensory perception and nociception Disturbances in these pathways are thought to be associated with the emotional and physical symptoms of depression References Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 8th ed. Baltimore, Md: Lippincott Williams & Wilkins; 1998:114-115. Fields HL, et al. Annu Rev Neurosci. 1991;14:219-245. Stahl SM. J Clin Psychiatry. 2002;63:382-383.

基底神经节 额前皮质 中脑边缘通路 中脑皮质通路 腹侧被盖区 黑质 参与协调运动功能。 与精神活动、思维、情感反应有关。

Treatment of mood disorders Medications Antidepressants (number of side effects) Monoamine oxidase (MAO) inhibitors (negative interactions with tyramine) Selective serotonergic reuptake inhibitors (SSRIs) (side effects) Lithium (weight gain, danger of poisoning) Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) as an alternative to ECT

抗抑郁药的发展史 1950s 1960s 1970s 1980s 1990s 2000+ 多作用机制抗抑郁药 （多受体作用） 选择性的抗抑郁药 （单一受体作用） 对多种单胺类靶目标有效的新药 1950s 1960s 1970s 1980s 1990s 2000+ 奈发唑酮 米氮平 文拉法辛 度洛西汀 丙咪嗪 氯丙咪嗪 去甲替林 阿米替林 去甲咪嗪 麦普替林 阿莫沙平 氟西汀 舍曲林 帕罗西汀 氟伏沙明 西酞普兰 Key Point Trends in psychopharmacology are again focusing on the role of multiple targets of action in the treatment of depression Background The modern era of psychopharmacology for depression began in the 1940s with the discovery of lithium; this was followed in 1950 by the synthesis of the antipsychotic agent chlorpromazine and continued with the discovery of the tricyclic antidepressant (TCA) imipramine. At approximately the same time, occasional euphoria was reported in tubercular patients treated with iproniazid, a monoamine oxidase inhibitor (MAOI). MAOIs began to be used as antidepressants in the 1960s The next major innovation was the availability of the first SSRI, fluoxetine, in 1988. The SSRIs lacked the dietary restrictions associated with MAOIs, and they offered safety and tolerability advantages over older tricyclic and heterocyclic agents Most recently, pharmacologic refinement has emphasized the potential combined role of NE and 5-HT in depression, as evidenced by the theoretical mechanism of action of venlafaxine. Unlike the SSRIs, which primarily inhibit only 5-HT reuptake, venlafaxine inhibits the reuptake of 5-HT and NE and has a side-effect profile similar to that of the SSRIs Venlafaxine is believed to work by inhibiting the reuptake of both 5-HT and NE Reference Lieberman JA. J Clin Psychiatry. 2003;5(suppl 7):6-10. 苯乙肼 异唑肼 Tranylcypromine 苯环丙胺 布普品 Lieberman JA. J Clin Psychiatry. 2003;5(suppl 7):6-10.

Treatment of mood disorders antimanic drugs ——mood stabilizers) 1ithium carbonate Ｌi+ →Na+ 、K+、Ca2+ 、Mg２+。 转运系统（ Na+ -K+） Ｌi 离子通道 29

“Are you prozac today？” 氟西汀 fluxetine，prozac “Are you prozac today？”

舍曲林 sertraline，zoloft 31

2.三环类抗抑郁药（TCAs)： 一线药: 疗效确切,价格低廉; 不良反应和禁忌症较多. 米帕明(imipramine， 丙米嗪 )、氯米帕明(clompramine，氯丙米嗪 ) 、多塞平(doxepin，多虑平 )、曲米帕明(trimipramine，三甲丙米嗪)。 第一代单胺摄取抑制药，非选择性，抑制NE和5-HT的再摄取，从而增加突触间隙这两种递质的浓度。 正常人服用米帕明后出现安静、嗜睡，但抑郁症病人连续服药后，出现精神振奋现象。疗效明显优于ＭＡＯＩ。起效慢，一般１～２周后始起效，２～３周疗效最佳。 不良反应较多，M受体阻断，抗胆碱作用，口干、便秘、排尿困难等。αl、Hl受体阻断：过度镇静。心脏毒性（体位低血压、心律失常、房室传导沮滞等）。 32

（3）选择性5-HT再摄取抑制剂 选择性高:抑制突触前膜对5-HT的回收。 药动学特性好:口服生物利用度高/半衰期都较长（18-26小时） 疗效好:优于ＴＣＡ,适用于各种类型抑郁症。 不良反应较少而轻微，抗胆碱及心脏副作用少， 注意:应避免与MAOIs等合用，否则易致5-HT过多的综合征。 目前为治疗抑郁症的一线药物： 氟西汀、帕罗西汀、舍曲林、 氟伏沙明和西酞普兰。 33

Treatment of mood disorders Psychosocial treatments Cognitive therapy Interpersonal therapy Combined treatments  V-Bipolar in depression (medication and psychosocial treatments) in bipolar disorders (combining medication and family and/or CBT is crucial)

Suicide 8th leading cause of death in the USA (30 000 people a year) for people aged 25-34 Among teenagers, suicide is the 3rd leading cause of death The suicide rate for young men in the USA is the highest in the world

Suicide Males are four to five times more likely to commit suicide than females 90% of suicides are committed by people suffering from psychological disorder 60% are associated with mood disorders 25%-50% with alcohol use and abuse 10% borderline personality disorder

Suicide Suicidal attempt Suicidal ideation Types of suicide (‘formalized’ suicide – altruistic suicide, egoistic suicide, fatalistic suicide etc.) Psychological autopsy (postmortem psychological profile of a suicide victim)

Suicide Imitation of suicide (teenager or celebrity) Suicide prevention cognitive-behavioral problem-solving approach strong social support and hopefulness treatment of psychiatric and personality disorders

谢谢！

Psychophysiology of Schizophrenia 四川大学华西医院康复医学科 郭华

Concepts Epidemiology Etiology Symptoms Diagnosis and differential diagnosis

Neuropsychology: Concepts A science that studies the relationship between the brain, nervous system and behavior. attempts to explain the way in which the activity of the brain is expressed in observable behavior

Concepts Schizophrenia comprises a group of psychotic disorders of unknown specific etiology often presented with a gradual onset of abnormalities in perception, thought, motion and behavior since young adulthood. A puzzling and profound psychological disorder. - It affects thought, perception, and mood. - loss of contact with reality.

Epidemiology Prevalence ： Point prevalence in China (1982): 4.75‰（rural area 3.42‰，urban 6.06 ‰ )。 Total prevalence in China(1982):5.69‰，(6.55 ‰ 1999)。 Lifetime prevalence in USA（1988）13‰。

Epidemiology Age：the age of onset in 50% of patients is 20~30 year old，over 80% of patients is 16~35year old. Gender： Schizophrenia occurs equally in men and women(in abroad) The prevalence in men is more than women (1.6:1) in China. The mean age of onset is about 2 to 5 years earlier in men than women.

Schizophrenia: Some Facts and Statistics (cont.) Gender differences in onset of schizophrenia in a sample of 470 patients

Etiology biological factors 1．genetics 2．The neurodevelopmental hypothesis 3．Changes in brain structure 4．Biochemical abnormalities personality factors psycho-social factors

Etiology Studies Method: Family studies Twin studies Adoption studies

Etiology The results of family studies: The risk of Schizophrenia. Schizoaffective disorder, and schizotypal personality is increased in first-degree relatives of patients with Schizophrenia. The risk of both Schizophrenia and mood disorder is increased in first-degree relatives of patients with schizoaffective disorder. The risk of bipolar illness is not increased in first-degree relatives of patients with schizophrenia.

Etiology The results of twin studies concordance rates among MZ pairs is higher than that among control(35-60 times) concordance rates are about 50% for MZ and about 10% for DZ. It might be expected that some environmental factors relevant to etiology. The risk of schizophrenia in the offspring of an unaffected twin is the same as that of an affected twin. This means that an unaffected twin has the same genetic susceptibility to developing Schizophrenia, but for some reason the susceptibility is not expressed.

Etiology The results of adoption studies The rate for Schizophrenia is greater among the biological relatives of the Schizophrenia Adoptees than among the relatives of control. The finding supports the genetic hypothesis.

Amino acids in Schizophrenia Biochemical studies The dopamine hypothesis. 5-HT hypothesis. Amino acids in Schizophrenia

感觉障碍(disorders of sensation) 感觉过敏(hyperesthesia) 感觉减退(hypoesthesia) Symptoms 感觉障碍(disorders of sensation) 感觉过敏(hyperesthesia) 感觉减退(hypoesthesia) 内感性不适(senestopathia) 知觉障碍（disturbance of perception） 错觉(illusion) 幻觉(hallucination) 感知综合障碍(psychosensory disturbance)

Symptoms Disorders of sensation and perception 幻听(auditory hallucination) 幻视(visual hallucination) 幻嗅(olfactory hallucination) 幻味(gustatory hallucination) 幻触(tactile hallucination) 内脏幻觉(visceral hallucination) 功能性幻觉（functional hallucination） 反射性幻觉（reflex hallucination）

Symptoms 思维形式障碍 (disorders of the thinking form) 思维贫乏(poverty of thought) 思维散漫( looseness of thought) 思维破裂(splitting of thought) 思维不连贯(incoherence of thought) 思维中断(blocking of thought) 思维被夺( thought deprivation)。 思维插入(thought insertion)和强制性思维(forced thinking) 思维化声(thought hearing) 思维扩散(diffusion of thought)和思维被广播(thought broadcasting) 象征性思维(symbolic thinking) 语词新作(neologism) 逻辑倒错性思维(paralogism thinking) 强迫观念（obsessive idea） 或称强迫性思维 内向性思维（autism）

Symptoms 妄想(delusion) 按其起源与其他心理活动的关系可分为原发性妄想(primary delusion)和继发性妄想(secondary delusion) 被害妄想(delusion of persecution) 关系妄想(delusion of reference) 物理影响妄想(delusion of physical influence)-被控制感。 钟情妄想(delusion of love) 嫉妒妄想(delusion of jealousy) 被洞悉感(experience of being revealed) 夸大妄想(grandiose delusion) 罪恶妄想(delusion of guilt) 疑病妄想（hypochondriacal delusion） 虚无妄想(delusion of negation)

Symptoms Three main kinds of mood are common: First, there may be sustained abnormalities of mood such as anxiety ,depression, irritability, or euphoria. Second, there may be blunting of affect. Essentially this is sustained emotional indifference（冷淡） or diminution of emotional response. Third, there is incongruity of affect. Here the expressed mood is not in keeping with situation or with the patient’s own feeling.

Symptoms Some acute patients are normal Others may present somewhat abnormalities of volition hypobulia abulia Parabulia（意向倒错） ambivalence paranoid schizophrenia may present hyperbulia

Symptoms Excitement（兴奋状态）----hebephrenic excitement, catatonic excitement Stupor（木僵）----. The patient remain motionless for a long time(catatonic stupor), or maintain their limbs or trunks in unusual positions(waxy flexibilitas ) for various lengths of time. Negativism（违拗）---- refuse to cooperate (active negativism, passive negativism) Passive obedience（被动服从）

Symptoms Stereotyped act-（刻板动作）---the patient repeat various functions or gestures, or imitate other’ movements(echopraxia 模仿动作) Mannerism（作态） Bizarre behavior（怪异行为） Forced act ， compulsive act Violence and suicide behavior Some patients may cause self-induced water intoxication or avoid eating because of certain delusional beliefs.

Auditory hallucinations 74 Delusions of persecution 64 Symptoms Symptom Frequency (%) Lack of insight 97 Auditory hallucinations 74 Ideas of reference 70 Suspiciousness 66 Flatness of affect 66 Delusional mood 64 Delusions of persecution 64 Thoughts spoken aloud 50

Diagnosis and differential diagnosis

Diagnosis The most recent definition was offered in 1994 in DSM-IV. Characteristic symptoms ( Delusions, hallucinations, disorganized speech, catatonic behavior, and negative symptoms.) Occupational dysfunction (work, interperonal relations, or self –care, academic, failure in goal achievement) Continuous signs of disturbance for at least 6 months with a least 1 month of active phase symptoms. 65

Evidence for the Dopamine Hypothesis Disorder Symptom Drug Action Effect treatment Calm Disordered thought and behavior 2. Causes tremors Schizophrenia Disordered thought and behavior Anti psychotic Decreases dopamine 66

Chronic schizophrenia Symptoms meeting the diagnostic criteria of schizophrenia; The course lasts for at least 2 years.

CCMD-3 diagnostic criteria Symptom criteria There is separate diagnostic criteria for simple type of schizophrenia: 1.Repeated auditory hallucinations that are usually not mood congruent; 2. Loosening of association, derailment, incoherence in thinking or poverty of thought 3.Thought insertion or withdrawal, thought block or forced thinking

CCMD-3 diagnostic criteria 4. Delusion of control, influence or passivity, thought broadcasting; 5. Primary delusions including delusional perception, delusional mood or other bizarre delusions; 6. Paralogic thinking, symbolic thought or neologism; 7. parathymia (情感倒错） or apathy; 8. Catatonic syndrome, unusual or silly behavior; 9. Avolition.

Differential diagnosis Some neurosis 1.the feature of insight 2.the feature of symptoms 3.some patients need to be following-up

Differential diagnosis Mood disorder Manic or severely depressed patients may exhibit psychotic symptoms during the peak of their disease states Accurate historical and clinical data should help to differentiate from mania-related psychotic features in the presence of other symptoms By the same token to differentiate depression from schizophrenia.

治疗与康复 急性治疗期（至少6周）、巩固治疗期（3－6个月）和维持治疗期（1年以上）。 1.药物治疗 早期、足量、足疗程、单一用药、个体化用药。根据病人情况、症状特点选择合适的药物。低量开始逐渐加量，高剂量密切观察不良反应。 急性治疗期（至少6周）、巩固治疗期（3－6个月）和维持治疗期（1年以上）。

抗精神病药物各自的靶症状 氯丙嗪 奋乃静 氟哌啶醇 利培酮 奥氮平 喹硫平 甲硫达嗪 泰尔登 舒必利 氯氮平 五氟利多 氟奋乃静癸酸酯

treatment of Schizophrenia 74

精神分裂症的维持治疗： 维持时间： 维持剂量： 首发2年维持 再发5年维持 三发以上终生维持 以往认为维持剂量为巩固治疗期剂量的1/2-1/3，甚至1/4-1/5左右。 现在认为维持量应为巩固治疗期剂量的2/3-3/4甚至全量。

2.电休克（ECT）治疗 3.心理与社会康复 慢性分裂症有退缩表现的患者可进行生活功能训练。 临床痊愈患者应鼓励参加社会活动和力所能及的工作。 慢性分裂症有退缩表现的患者可进行生活功能训练。

谢谢！