临床神经学：mood disorder and schizophrenia - Julie

1、临床神经科学Mood disorderIntroductionMood is the internal emotional state of a person. Mood Disorders are a group of clinical conditions that are characterized by a loss of sense of control of the mood and a sense of great distress.IntroductionMood Disordersdepressive disorderbipolar disorderMood Disorder

2、sMood DisordersMood DisordersEpidemiologyUnipolar depression is the most common psychiatric disorders of adult psychiatric disorders of adult. Lifetime prevalence for unipolar depression is approximately 6%; the lifetime prevalence of bipolar depression is approximately 1%Gender Two fold greater pre

3、valence of depression in women than in menBipolar disorder prevalence is 0.5%-1%;3:2 in woman:manAgeOnset can occur at any age, but 50% have onset between age 20 to 50Mood DisordersEpidemiologyDepressionhigh cost to the society and account for 10.5% of all costs of biomedical illness worldwideRanked

4、 the 4th in Global Disease and projected to be the 2nd by year 2020 (WHO, 2001)In Hong Kong it was estimated that the lifetime prevalence of this group is about 1.4% for males and 2.6% for femalesDepression Bipolar disorderAetiologyAetiologyBehaviour and BrainHormones and BrainWhile most of the horm

5、ones affect the brain in one way or another, we only focus on the two systems most relevant to mental illness: the hypothalamic-pituitarythyroid (HPT) axis the hypothalamic-pituitary-adrenal (HPA) axis.THE HYPOTHALAMIC- PITUITARY-THYROID AXISThe important point is that tetraiodothyronine (T4) and tr

6、iiodothyronine (T3) have direct effects on the brain as well as the body. Common Clinical Features of Abnormal Thyroid FunctionHYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND STRESSNote that adrenocorticotropic hormone (ACTH) releases an array of hormones with a diurnal variation. As with all hormones, ther

7、e are direct effects on the cerebral cortex. CNS, central nervous system; CRH, corticotropin-releasing hormone.The Depressed BrainStructural imaging, functional imaging, and postmortem studies have established five regions that are consistently dysfunctional in most patients with depression. Note th

8、e extensive prefrontal involvement.Anhedonia(快感缺乏) can be attributed to dysfunction of the nucleus accumbens（伏核） or cognitive deficits to the anterior cingulate cortex（扣带回）. However, while a few symptoms seem to match up with a brain region, most do not. Most symptoms are likely the product of simul

9、taneous dysfunction in several regions.The Depressed BrainSTRESSRats exposed to high stressmesh wire retainershow shrinkage of dendrites in the hippocampus and impairments in the kinds of memory that depend on the hippocampus (Kleen, Sitomer, Killeen, & Conrad, 2006).pregnant rats-infants-adulthood-

10、 decreased plasticity in the hippocampus and im-pairments of spatial learning (Brunson et al., 2005; Mirescu. Peters, & Gould, 2004; Son et al., 2005)Cortisol metabolic activityModerated attention, memory, immune systemProlongedVulnerability of cells in the hippocampusAdaptability of hippocampal neu

11、ronsTHE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS肾上腺皮质醇BDNF in PFC and hippocampus脑源性神经营养因子The Depressed BrainAlternatively, it is possible to envision depression as the result of overactivity in some regions and underactivity in others. For example, the hippocampus and nucleus accumbens are considered un

12、deractive in depressed patients, whereas the hypothalamic-pituitary-adrenal (HPA) axis and amygdala are overactive. This is appealing because some of the symptoms of depression appear to be caused by loss of function (low motivation, lack of hope, and low appetite), whereas others appear to be cause

13、d by hyperactivity (insomnia, anxiety, and suicidal thoughts)The Depressed BrainPET scans for a patient with bipolar disorderCicradianRhythmsAetiology Psychosocial FactorsLife events and environmental stress e.g. poverty, loss of parents, loss of spouse配偶Premorbid personality, hysterical歇斯底里Learned

14、helplessnessHolmes & Rahe Stress ScaleGENE and LIFE EVENTSTreatmentTreatmentsBrain scans show that antidepressants and psychotherapy increase metabolism in the same brain areas (Brody et al., 2001; S. D. Martin et al., 2001).THANK YOU!临床神经科学Schizophrenia王凤怡 Julie 华西医院康复医学中心作业治疗部HISTORIC PERSPECTIVEO

15、ver 100 years ago, Emil Kraepelin, a German psychiatrist, described the syndrome now called schizophrenia.IntroductionA disturbance that lasts for at least 6 months and includes at least 1 month of active-phase symptoms (i.e. two or more of the following: delusions, hallucinations, disorganised spee

16、ch, grossly disorganised catatonic紧张的 behaviour, negative symptoms). A group of characteristic positive or negative symptoms; deterioration in social, occupational, or interpersonal relationshipsPercent developing schizophreniaPercent developing schizophreniaThe typical clinical course of schizophre

17、niaClinical featuresPositive symptoms Reflect an excess or distortion of normal function ( 1 month- duration of two or more positive symptoms)Negative symptoms Reflect a decrease or deficit of normal functionClinical features-positiveDelusions妄想false beliefs strongly held in spite of invalidating ev

18、idence, especially as a symptom of mental illness:Paranoid delusions, or delusions of persecution, for example believing that people are out to get youDelusions of reference - when things in the environment seem to be directly related to you even though they are not. Somatic Delusions are false beli

19、efs about your body - for example that a terrible physical illness exists or that something foreign is inside or passing through your body. Delusions of grandeur - for example when you believe that you are very special or have special powers or abilities. An example： You are a famous movie starDelus

20、ions of thought insertion/thought telepathy thought broadcasslides contributed by Dr A Cheng & Dr M YaClinical features2. Hallucinations幻觉Hallucinations can take a number of different forms:Visual (seeing things that are not there or that other people cannot see) Auditory (hearing voices that other

21、people cant hear) Tactile (feeling things that other people dont feel or something touching your skin that isnt there) Olfactory(smelling things that other people cannot smell, or not smelling the same thing that other people do smell)Gustatory experiences (tasting things that isnt there)Clinical fe

22、atures3. Disorganized speechFrequent derailment or incoherence Person seems to talking to himself/herself or imagined people or voices4. Grossly disorganized or catatonic紧张 behaviorAn abnormal condition variously characterized stupor昏迷/inactivity, mania, and either rigidity or extreme flexibility of

23、 the limbsClinical features-positiveAetiologyGenetic & Neurbiological Contribution Dopamine Hypothesis: when the gene, COMT 儿茶酚氧位甲基转移酶 is abnormal. neurons and dendrites developmental abnormality cerebral ventricular enlargement脑室扩大 significant Loss of Brain Gray MatterClinical features-negativeLack

24、 of emotion the inability to enjoy regular activities (visiting with friends, etc.) as much as before 2. Low energy the person tends to sit around and sleep much more than normal 3. Lack of interest in life, low motivation 4. Affective flattening 情感冷漠a blank blunted facial expression or less lively

25、facial movements, flat voice (lack of normal intonations and variance) or physical movementsClinical features-negative5. Alogia (difficulty or inability to speak)6. Inappropriate social skills or lack of interest or ability to socialize with other people 7. Inability to make friends or keep friends,

26、 or not caring to have friends 8. Social isolation -person spends most of the day alone or only with close familyClinical features-others Lack of insight Disorganized thinking Slow thinking Difficulty understanding Poor concentration Poor memory Difficulty expressing thoughts Difficulty integrating

27、thoughts, feelings and behavior Alcohol and drug abuseClinical featuresTypes paranoid type偏执型（妄想）catatonic type紧张性（精神机能障碍）residual type残余型Disorganized type 混乱型（言语、行为不协调）other schizophrenia 其他型AetiologyGenetic ContributionAetiologyGenetic & Environmental ContributionAetiologyNeurobiological basisRedu

28、ced Neuropil Hypothesis神经网络减少假说The regions were Brodmanns areas 9 and 46 in the prefrontal cortex(PFC) and area 17 in the visual cortex.A. Schematic representation of the increased density but decreased size of schizophrenic gray matter. B. Suspected neuronal atrophy of schizophrenic pyramidal neuro

29、ns椎体神经元, which results in defective connectivity. (A adapted from Selemon LD. Increased cortical neuronal density in schizophrenia. Am J Psychiatry.2004;161(9):1564.)The tighter packaging of the schizophrenic neurons results from reduced cell size, less branching, and decreased spine formation.These

30、 results suggest that the cognitive impairment in patients with schizophrenia comes from impaired frontal lobes. Atrophic, disconnected neuronal cells presumably cause the PFC dysfunction.oligodendrocyte reductionPatients were asked to press a button with the onset of hallucinations and keep it pres

31、sed for as long as they lasted. Images during hallucinations were compared with images when the voices were silent.AetiologyEnvironmental contributionChild and young adult schizophrenia risk factorsQuestions All of the following support the reduced neuropil hypothesis, excepta. Oligodendrocyte dysfu

32、nction.b. Reduced neural cell size.c. Limited spine formation on the dendrites.d. Increased density of gray matter.QuestionsAuditory hallucinations have been shown to activate which region on fMRI?a. Superior temporal lobe.b. Brocas area.c. Wernickes area.d. Arcuate fasciculus.videoTreatmentPrincipl

33、es of handling the person with an acute episode of schizophreniaDuring hospitalisation of the patient with schizophrenia, the occupational therapist is often confronted with bizarre, psychotic behaviour. The handling of the patient by the occupational therapist in a calm and consistent manner is imp

34、ortant in bringing the patient in touch with realityThe patient must never be ridiculed or laughed at because of his/her bizarre ideas, delusions or hallucinationsBe gently reminded of reality.Gently remind the patient of the time of day and date and orientation to place.Handle aggression calmly and

35、 try to channel it into activity with wide movements.Gently correct unacceptable behaviour. Do not be punitive in approachOccupational group therapy Personal care groups/self-independence and assistance in the familys daily tasks. Creative activity groups which should include hobby or leisure pursui

36、tsIf there is no sensory integration programme, simple exercise groups, walks and sport, such as volleyball, are very important for physical fitness. Social skills training groups which include communication skills training, when the psychotic features are diminished, are very important in order to counteract pervasive deficits in so