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1、2022/12/21,1,Bipolar and Related Disorders & Depressive Disorders,2022/12/21,2,Overview,What is bipolar disorders and depressive disorders?Criteria for specific mood episodes and disordersEpidemiology and aetiology of bipolar disorders and depressive disordersAcute and long-term management of mood d
2、isorders.,2022/12/21,3,What is a mood disorder?,Mood is a persons subjective emotional stateAffect is the objective appearance of moodMood disorders (according to DSM-IV) involve a depression or elevation of mood as the primary disturbance.Can have other abnormalities (psychosis, anxiety, etc.),2022
3、/12/21,4,2022/12/21,5,Introduction,Depression depressed mood negative thinking lack of enjoyment reduced energy slowness,Mania elevated or irritable mood over-activity self-important ideas,2022/12/21,6,Major Depressive Episode_DSM-IV,Depressed moodAnhedoniaDecrease or increase in appetite OR signifi
4、cant weight loss or gainPersistently increased or decreased sleepPsychomotor agitation or retardation,Fatigue or low energyFeelings of worthlessness or inappropriate guiltDecreased concentration or indecisivenessRecurrent thoughts of death, suicidal ideation, or suicide attempt,Five or more symptoms
5、 present for 2 weeks,Major Depressive Episode_DMS-5,2022/12/21,7,2022/12/21,8,2022/12/21,9,Moderate Depressive Episode,AppearanceDepressive cognition worthlessness, pessimism, guiltGoal-directed behaviorPsychomotor retardation or agitationBiological symptoms sleep disturbance, weight loss, physical
6、symptomsOther features,2022/12/21,10,Severe Depression and Psychotic Depression,Greater intensity of symptomsComplete loss of function in social and occupational sphereInattention to basic hygiene and nutritionDelusions and hallucinations Cotards syndrome,2022/12/21,11,Other Clinical Features of Mod
7、erate and Severe Depression,Agitated depressionRetarded depressionDepressive stuporAtypical depression variably depressed mood overeating and oversleeping extreme fatigue and heaviness in the limbs pronounced anxiety,2022/12/21,12,Emile KraepelinManic-Depressive Insanity1928 (English Edition),Depres
8、sive Stupor,2022/12/21,13,Mild Depressive States,Additional symptoms (neurotic) anxiety phobias obsessional symptoms dissociative symptoms,2022/12/21,14,Mania,Central features: Elevation of mood increased activity self-important ideas,2022/12/21,15,Mania,Emile KraepelinManic-Depressive Insanity1928
9、(English Edition),2022/12/21,16,2022/12/21,17,Clinical Features,Mood infectious gaietyAppearance and behavior untidy and dishevelled, physical exhaustionSpeech and thought rapid and copious, flight of ideas, expansive ideas, extravagant, grandiose delusionPerceptual disturbances hallucinationOther f
10、eatures impaired insight,2022/12/21,18,Manic Episode_DSM_IV,A. Elevated (or irritable) mood for 1 weekB. Three or more of following (four if mood irritable):,GrandiosityDecreased need for sleepPressured speechFlight of ideas, racing thoughts,DistractibilityIncreased goal-directed activityExcessive i
11、nvolvement in pleasurable activities with high risk,Manic Episode_DSM-5,2022/12/21,19,Manic Episode_DSM-5,2022/12/21,20,2022/12/21,21,Specific Clinical Type(DSM-IV),Mixed Mood DisorderRapid Cycling DisorderManic Stupor,Clinical Features(DSM-5),2022/12/21,22,Classification of Mood Disorder,Classifica
12、tion of DepressionBased on presumed aetiologyBased on symptomatic pictureBased on course,2022/12/21,23,Classification by presumed aetiology,Endogenous depressionReactive depression,2022/12/21,24,Classification by symptomatic picture,Melancholic depression More severe symptomatology Poor response to
13、placebo medication Good response to ECT More evidence of neurobiological abnormalitiesPsychotic depressionNon-melancholic depression,2022/12/21,25,Classification by course,Unipolar and bipolar disorderSeasonal affective disorder hypersomnia increased appetite with craving for carbohydrate afternoon
14、slump in energy,2022/12/21,26,Classification in ICD and DSM,2022/12/21,27,Classification of bipolar disorder,ICD-10 DSM-IV Manic episode Hypomanic episode Hypomania Manic episode Mania (Mild, Moderate, Severe, Severe with psychosis) Mania with psychosis Bipolar affective disorder Bipolar I and bipol
15、ar II disorder Currently hypomanic Current (or most recent episode) Hypomanic Currently manic Manic Currently depressed Depressed Currently mixed Mixed In remisson Cyclothymic disorder Cyclothymia,2022/12/21,28,Classification of Depressive Disorder(1),ICD-10 DSM-IV Depressive episode Major depressiv
16、e episode Mild Mild Moderate Moderate Severe Severe Severe with psychosis Severe with psychosis Other depressive disorder Atypical depression Recurrent depressive disorder Major depressive disorder Recurrent Currently mild Currently moderate Currently severe Currently severe with psychosis In remiss
17、ion,2022/12/21,29,Classification of Depressive Disorder(2),ICD-10 DSM-IV Persistent mood disorder Dysthymic disorder Cyclothymia Dysthymia Other mood disorder Depressive disorder not otherwise specified Recurrent brief depression Recurrent brief depression,2022/12/21,30,A systematic scheme for the c
18、linical description of mood disorders,Severity Mild, moderate, or severeType Depressive, manic, mixedSpecial features With melancholic symptoms With atypical symptoms With prominent anxiety With psychosis symptoms With agitation With retardation or stuporThe coures Unipolar or bipolar Aetiological f
19、actors Organic Family history of mood disorder Personal history of mood disorder Childhood experience Personality Social support Life events,Depressive Disorders-DSM-5,2022/12/21,31,Bipolar and Related Disorders(DSM-5),2022/12/21,32,2022/12/21,33,Differential diagnosis,Depressive disorderNormal sadn
20、essAnxiety disordersSchizophrenia Organic brain syndromesManiaSchizophreniaOrganic brain disease involving the frontal lobesStates of brief excitement induced by amphetamines and other illicit drugs.,2022/12/21,34,The Epidemiology of Mood disorder,Bipolar disorderthe lifer time risk for bipolar diso
21、rder lies between 0.3 and 1.5 per centThe 6-month prevalence of bipolar disorder is not much less than the lifetime prevalence, indicating the chronic nature of the disorder.The prevalence in men and women is the same.The mean age of onset is about 17 years of age in community studies.Bipolar disord
22、er is highly comorbid with other disorders, particularly anxiety disorders and substance misuse.,2022/12/21,35,The Epidemiology of Mood disorder,DepressionThe 12-month prevalence of major depression in the community is between 2 and 5 per cent.The lifetime rates in different studies vary cosiderably
23、 (4-30 per cent). The true figure probably lies between 10 and 20 per cent.The mean age of onset is about 27 years.Rates of major depression are about twice as great in woman as men, across different cultures.There may be increased rates of depression in people born since 1945.Rates of depression ar
24、e higher in the unemployed and divorced.Major depression has a high comorbidity with other disorders, particularly anxiety disorder and substance misuse.,2022/12/21,36,The aetiology of mood disorder,Area of investigation relevant studiesGenetic Genetic epidemiology Molecular geneticsPersonality Temp
25、erament Cognitive styleEarly environment Parental deprivationSocial environment Life eventsPsychological PsychodynamicBiological Monoamines HPA axis Neuropsychology,2022/12/21,37,Genetic causes,Family and twin studiesFamilial aggregationTwin studiesGenetic evidence on classification of mood disorder
26、Molecular geneticsLinkage studiesAssociation studies,2022/12/21,38,Personality,Cyclothymic personality were more prone to develop bipolar disorderSome personality features may influence the way that people respond to adverse circumstance and thus make depressive disorder.Certain kinds of personality
27、 development and psychiatric disorder may share common genes, such as neuroticism.,2022/12/21,39,Early Environment,Parental deprivation Psychoanalysts have suggested that childhood deprivation of maternal affection through separation or loss predisposes to depressive disorders in adult life.Relation
28、ships with parents physical and sexual abuse, parental style, non-caring, overprotective parenting,2022/12/21,40,Precipitating Factors,Recent life events Studies suggest that events lead to feelings of entrapment and humiliation may be particularly relevant to the onset of depression. Clinical exper
29、ience suggests that a proportion of manic cases are precipitated, sometimes by events that might have been expected to induce depression, for example, bereavement.,2022/12/21,41,Precipitating Factors,Vulnerability factors and life difficulties long-term difficulties vulnerability factor: have the ca
30、re of young children, not working outside the home, having no one to confide in. poor social supportThe effects of physical illness,2022/12/21,42,Psychological approaches to aetiology,Psychoanalytical theory Freud 1911Cognitive theory negative thoughts (automatic thoughts): cognitive distortions arb
31、itrary inference selective abstraction overgeneralization personalization,2022/12/21,43,Neurobiological approaches to aetiology,The monoamine hypothesis: Depressive disorder is due to an abnormality in a monoamine neurotransmitter system at one or more sites in the brain. serotonin (5-HT) noradrenal
32、ine (NE) dopamine (DA),2022/12/21,44,5-HT,Abnormalities in depressionDecreased plasma tryptophanDecreased brain 5-HT1A receptor binding (PET)Decreased brain 5-HT re-uptake sites (SPET)Blunted 5-HT neuroendocrine responsesClinical relapse after tryptophan depletion,2022/12/21,45,Noradrenaline,Abnorma
33、lities in depressionBlunted noradrenaline-mediated growth hormone releaseClinical relapse after AMPT,2022/12/21,46,Dopamine,Abnormalities in depressionDecreased homovanillic acid (HVA) levels in CSFIncreased dopamine D2 receptor binding (PET/SPET) Clinical relapse after AMPT,2022/12/21,47,Role of mo
34、noamines,The studies that shows a key role for monoamines in the pathophysiology of depression are the 5-HT and catecholamine depletion paradigms.It is now established that in vulnerable individuals, lowering of 5-HT and noradrenaline and dopamine function is sufficient to cause clinical depression.
35、,2022/12/21,48,Two major question?,How does altered monoamine function impact on the cortical circuitry involved in mood regulation?How does altered monoamine function contribute to the clinical symptomatology of depression.,2022/12/21,49,Endocrine abnormalities,Some disorder of endocrine function a
36、re followed by mood disorders more often than would be expected by chance, suggesting a causative relationship.Endocrine abnormalities found in depressive disorder indicate that there may be a disorder of the hypothalamic centres controlling the endocrine system.,2022/12/21,50,Endocrine pathology an
37、d depression,Plasma cortisolDexamethasone Suppression Test (DST) Dexamethasone non-suppression is more common in depressed patients with melancholiaGlucocorticoid Receptor HypothesisHypersecretion of CRH.,2022/12/21,51,Cortisol, monoamine function, and neuronal toxicity,Expression of post-synaptic 5
38、-HT1A receptors in the hippocampusExcessive cortisol secretion to damage to neurons in the hippocampus,2022/12/21,52,Thyroid function,Level of free triidothyronine may be decreased in depressed patients.Blunted thyrotropin-stimulating hormone(TSH),2022/12/21,53,Depression and the immune system,Lower
39、ed proliferative response of lymphocytes to mitogensLowered natural killer cell activityIncrease in positive acute phase proteinsIncrease in cytokine levels (e.g. IL-1, IL-6),2022/12/21,54,Sleep changes in depression,Impaired sleep continuity and durationDecreased deep sleep (stage 3 and 4)Decreased
40、 latency to the onset of rapid eye movement (REM) sleepIncrease in the proportion of REM sleep in the early part of the night,2022/12/21,55,Brian imaging in mood disorder,change in brain volume: enlarge lateral ventricle; decreased hippocampal volume decreased volume of basal ganglia structures; dec
41、reased grey matter volume of sub genual prefrontal cortex; increased amygdala volume,2022/12/21,56,Brian imaging in mood disorder,White matter hyperintensities In major depression, hyperintense MRI signals are associated with: late onset of depressive disorder; greater illness severity and poorer tr
42、eatment response; apathy, psychomotor slowness, and retardation; presence of vascular risk factors,2022/12/21,57,Brian imaging in mood disorder,Cerebral blood flow and metabolism: Depressed patients have evidence of altered cerebral blood flow and metabolism in: prefrontal cortex; anterior cingulate
43、 cortex; amygdala and thalamus; caudate nucleus,2022/12/21,58,Neuropsychological changes in mood disorder,Impairment is typically seen over a wide range of neuropsychological domains including attention, learning, memory, and executive function.Some have suggested that deficits in executive function
44、 may be particularly prominent which would be consistent with abnormalities seen in prefrontal perfusion in imaging studies.,2022/12/21,59,AETIOLOGY-CONCLUSION,2022/12/21,60,Genes & Temperament,DevelopmentalExperience,Modulating ParametersAge, Sex, Endocrine (HPA axis function), Immunity etc,Precipi
45、tating FactorsLife Events, Biological Insult,Stress Response:Perturbed Neurochemistry(NA function; 5-HT function),LIMBIC-DIENCEPHALICDYSREGULATION,MOOD DISORDER,A Common Pathway to Mood Disorder,2022/12/21,61,Course and Prognosis,Bipolar disorders the age of onset; the average length of a manic epis
46、ode; 90 per cent of patients experience further episode of mood disturbance; the interval between episodes; the long-term prognosis is poor.,2022/12/21,62,Course and Prognosis,Unipolar depressive disorders the age of onset; the average length of a depressive episode; 80 per cent of patients experien
47、ce further episodes. the interval between episodes; long-term prognosis may be a little better than that of bipolar disorder.,2022/12/21,63,Mortality of mood disorder,Mortality ratio in mood disorders is about twice that found in the general population.Rates of suicide in mood disorders is at least
48、12 times greater than those of the general population.Standardized mortality ratios: major depression 20.35 bipolar disorder 15.05 dysthymia 12.05,2022/12/21,64,Prognostic Factors,Incomplete symptomatic remissionBipolar disorderEarly age of onset Poor social supportComorbid substance misuseComorbid
49、personality disorder,2022/12/21,65,Acute Treatment of Depression,Antidepressant drugsLithiumAnticonvulsantsElectroconvulsive therapyPsychological treatment Other treatments,2022/12/21,66,Antidepressant drugs,Tricyclic antidepressantsMonoamine oxidase inhibitors (MAOIs)Selective serotonin re-uptake i
50、nhibitors (SSRIs) Serotonin and noradrenaline re-uptake inhibitors (SNRIs)Other antidepressants,2022/12/21,67,Lithium,Placebo-controlled trials suggest that lithium has antidepressant efficacy in bipolar but its effects in unipolar depression as a sole treatment are modest.More usual pattern of resp
