mood disorders tung-ping tom su, md department of psychiatry national yang-ming university veterans...
Post on 21-Dec-2015
218 views
TRANSCRIPT
![Page 1: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/1.jpg)
Mood Disorders
Tung-Ping Tom Su, MDTung-Ping Tom Su, MD
Department of PsychiatryDepartment of PsychiatryNational Yang-Ming UniversityNational Yang-Ming University
Veterans General Hospital-TaipeiVeterans General Hospital-Taipei
Sept. 28, 2010 (Yang-Ming IBS lecture)Sept. 28, 2010 (Yang-Ming IBS lecture)
![Page 2: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/2.jpg)
憂鬱症之流行病學:美國重鬱症之病發率
Regier et al., 1988; Blazer et al., 1994
2.2
4.95.8
17.1
0
5
10
15
20
Epidemiologic CatchmentArea (ECA)
National ComorbiditySurvey (NCS)
Percentof Patients
point prevalence (30 day)
lifetime prevalence
![Page 3: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/3.jpg)
The Burden of Bipolar DisorderThe Burden of Bipolar Disorder
• Sixth leading cause of disability worldwide
• Higher risk of cardiovascular disease
• High economic costs ($45.2 billion in US in 1991)
• Sixth leading cause of disability worldwide
• Higher risk of cardiovascular disease
• High economic costs ($45.2 billion in US in 1991)
6th Bipolar disorder
7th War
8th Violence
9th Schizophrenia
Woods. J Clin Psychiatry. 2000;61(suppl 13):38-41; Ahrens et al. Can J Psychiatry. 1995;40:241-246; Wyatt and Henter. Soc Psychiatry Psychiatr Epidemiol. 1995;30:213-219.
DIS
AB
ILIT
Y
![Page 4: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/4.jpg)
Prevalence of Prevalence of ‘‘treated treated depression’depression’
Age by genderAge by gender
Neel L Burton: Psychiatry, 2007, Blackwell publishing
Biological:• Genetic predisposition • Horrmonal influencesSociocultural:• Social pressure• Readiness to admit depressive Sx• Diagnostic bias
![Page 5: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/5.jpg)
Classification of mood disorders
Neel L Burton: Psychiatry, 2007, Blackwell publishing
![Page 6: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/6.jpg)
Clinical course ofClinical course ofMood disordersMood disorders
Recurrent depression
Dysthymia
Bipolar depression (bipolar I)
Cyclothymia
Neel L Burton: Psychiatry, 2007, Blackwell publishing
Dysthymia & double depression
![Page 7: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/7.jpg)
Epidemiology (prevalence): USA data
• Major depressive d/o: M: 2.6 - 5.5%, F: 6 - 11.8% (Fava’96) – MDD higher in separated/divorced male, unemployed and
medically ill pts. – Primary care: 4.8-9.2% (MDD) and 9 - 20% (all depressive
d/o)
• Dysthymia: 3 - 4% (Keller 1996)
• Bipolar d/o: – Lifetime risk & 6 month prevalence : 0.3-1.5% (nature:
chronicity) – 1/3 of primary D met criteria for bipolar spectrum d/o and
risk of bipolarity is higher in children and adolescent (32% and 20%)
– Lifetime rate across culture: 0.3/100 (Taiwan) to 1.5/100 (N.Z)
![Page 8: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/8.jpg)
憂鬱症之診斷標準憂鬱症之診斷標準
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
![Page 9: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/9.jpg)
Major depressive episode (1)
• Occur in both major depression and bipolar d/o
• 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)
![Page 10: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/10.jpg)
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, excessive guilt and agitation/retardation
• Seasonal affective d/o (winter depression)
– Hypersomnia, carbohydrate craving, overeating, weight gain
and fatigue
![Page 11: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/11.jpg)
Dysthymic disorder (1)
MD MD
• Sx: depression and > 2 sxs of– Changes in appetite, sleep, energy, low self-esteem,
distractibility, decision making and hopelessness– Sx never been free > 2 months at a time– No major depressive episode in the first 2 years
• Dysthymic D vs. MDD: – cognitive & motivational vs. vegetative Sx, – 80% of dysthymia have lifetime MDD
Double depression
Chronic dysthymic d/o (DD)
>= 2 years>=1 yr: children& adolescent
![Page 12: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/12.jpg)
臨床憂鬱症之多型性型態臨床憂鬱症之多型性型態
憂鬱症憂鬱性精神病
內科疾病相關憂鬱症
女性相關憂鬱症
重鬱症 單極性憂鬱症
雙極性憂鬱症
器質性憂鬱症
慢性輕鬱症
憂鬱性格精神疾病共病憂鬱症
![Page 13: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/13.jpg)
Comorbidity of affective disorders
Affective disorders
Medical illness
Substance abuse Schizophrenia
Phobia, Panic d/o,
Personality d/o
OCD
25 – 50%
30 – 70%
50 – 60%
30 – 90%30 – 40%
![Page 14: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/14.jpg)
Neurobiological model of the pathophysiology of major depression
Oxford Textbook of Psychiatry, 5th ed, 2006Oxford Textbook of Psychiatry, 5th ed, 2006
Adverse childhood experience
Current stress
HPA axis function
Genetic factors
Past depressive episode
Cortisol
NA function 5-HT function
Prefrontal cortex hippocampus
Depressive syndromeDepressive syndrome
![Page 15: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/15.jpg)
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
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0 1 2 3 4+
l/l
s/l
s/s
Number stressful life events
Pro
bab
ilit
y o
f M
DE
Caspi, A et al SCIENCE 301; 386 ff, JULY 18, 2003
![Page 16: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/16.jpg)
Major depressive disorder: biological model
• Stronger genetic basis:– Monozygote > dizygote (bipolar > MDD) (Gershon 1990)
– Unipolar and bipolar may coexist in a twinship
– Risk of major affective d/o: one bipolar parent: 29.5%, two parents
with affective d/o with one bipolar: 74%
• Biochemical (neurotransmitters): – 5-HT, NE, DA (uptake inhibition)– Receptor sensitivity: beta-adrenergic receptor downregulation
• Neuroendocrinology:– HPA axis: cortisol releasing factor (CRF) overdrive– HPT axis: blunted TSH response to TRH, T3 augmentation
• REM latency (< 65 min): marker (endogenous depression)
![Page 17: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/17.jpg)
Hypothalamo-pituitary-adrenal axis (HPA) system during acute stress
![Page 18: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/18.jpg)
Hypercortisolemia in depression
![Page 19: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/19.jpg)
Response to stress in normal, major depression and PTSD
MDDMDD
DST:DST:DEX, 1mg,DEX, 1mg,cortisol >=0.5 ug/dlcortisol >=0.5 ug/dl
PTSDPTSDNormalNormal
![Page 20: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/20.jpg)
憂鬱症之藥物治療憂鬱症之藥物治療
•從輕至重度憂鬱症均有效
•有效率 60-80%
•治療目標為症狀緩解、功能恢復及預防再發
![Page 21: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/21.jpg)
Serotonergic pathway
![Page 22: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/22.jpg)
![Page 23: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/23.jpg)
How SSRIs work to depression
Paul Harrison Lecture note of Psychiatry, 2006Blackwell publishing.
![Page 24: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/24.jpg)
![Page 25: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/25.jpg)
Major depressive disorder: therapy
• Remission (6M-1 yr) & recovery (>1yr), relapse (6M-1yr) and recurrence (>1 yr)
• Psychotherapy– supportive, brief psychodynamic , interpersonal
psychotherapy (IPT) and cognitive therapy (CT), cognitive-behavior therapy (CBT)
• 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: seasonal affective d/o• Exercise: mild to moderate depression
![Page 26: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/26.jpg)
Development of antidepressantDevelopment of antidepressantfrom past to futurefrom past to future
1950
TCAs
1985
SSRIs:fluoxetinesertralineparoxetinecitalopramfluoxamine
1990
NDRI:bupropion
2000
SNRIs:venlafaxinemirtazapineduloxetineminacipran
2005
CRF antagonistSP antagonistAgomelatine
Targeting on CREB-BDNFsignalingcascade enzymes
![Page 27: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/27.jpg)
The five major regions of dysfunction in depressed brains
and Nu. Accumbens are underactivity and HPA axis: overactivity
![Page 28: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/28.jpg)
![Page 29: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/29.jpg)
![Page 30: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/30.jpg)
New Concept of Treatment New Concept of Treatment in Psychiatric Disorders: in Psychiatric Disorders:
• TMS TMS (transcranial magnetic stimulation)(transcranial magnetic stimulation)
• VNS VNS (vagnus nerve stimulation)(vagnus nerve stimulation)
• DBS DBS (deep brain stimulation)(deep brain stimulation)
![Page 31: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/31.jpg)
Repetitive Transcranial Repetitive Transcranial Stimulation (rTMS)Stimulation (rTMS)
Time-varying electrical current in a coil produces
Focal 2 tesla magnetic field
Passes unimpeded through skull induces current in neurons
Behavioral change
![Page 32: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/32.jpg)
Biomarkers predicting rTMS efficacy in Medication-Resistant Depression:
a 18F-FDG PET studyCheng-Ta Li/ Tung-Ping Su
980727
![Page 33: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/33.jpg)
Hypotheses and Aims• Responders are different from non-responders in
resting brain metabolism– Differences may account for core antidepressant
mechanism of rTMS
• Pre-rTMS regional brain glucose uptake in DLPFC, ACC, hippocampus and brainstem may – Predict rTMS effectiveness in medicated MRD patients.
• Underlying pathophysiology of MRD is different from other depressives ?– Compare with previous hypothesis of depression
![Page 34: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/34.jpg)
Results
![Page 35: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/35.jpg)
Study design for rTMS in treatment refractory depressed
![Page 36: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/36.jpg)
Treatment-Resistant MDD (20) vs. NC (20)
NC < MDDNC > MDD
•Global variance across scans: removed by analysis of covariance (ANCOVA)•Btw-gp comparison: ANCOVA, Controlling for age and gender•Cluster level, controlled p <0.001
![Page 37: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/37.jpg)
Treatment-Resistant MDD (20) vs. NC (20) A cortico-limbal dysregulation
• MDDBil DLPFCBil OFCBil Med. PFC Bil Ant. Insula - IFAAnterior CingulumMiddle Cingulum
Bil AmygdalaBil Putamen/GP Bil InsulaHippo/ParahipRaphe nu. Cerebellum
![Page 38: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/38.jpg)
Responder(13) vs. Non-Responder(7)• Responders
Bil DLPFC (BA 9) Bil OFC Bil Med. PFC (BA 6d)Anterior CingulumMiddle Cingulum
Bil Uncus/FusiformBil Srtiatum Bil InsulaHippo/ParahipRaphe nu. Cerebellum
•Voxel level, k=300, uncontrolled p <0.05
![Page 39: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/39.jpg)
Less hypoactive in ACC, bilateral medial prefrontal gyrus
Responder > N-R
•Global variance across scans: removed by analysis of covariance (ANCOVA)•Btw-gp comparison: ANCOVA, Controlling for age and gender•Using NC vs. MDD mask•Cluster level, k=2000,uncontrolled p <0.05
![Page 40: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/40.jpg)
Less hyperactive in left hippocampus and fusiform gyrus
Responder < N-R
•Global variance across scans: removed by analysis of covariance (ANCOVA)•Btw-gp comparison: ANCOVA, Controlling for age and gender•Using MDD vs NC mask•Cluster level, k=1000,uncontrolled p <0.10
![Page 41: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/41.jpg)
Pre-tx areas predicting treatment responses (≥50% decreases in HDRS)
•Higher pre-tx metabolism in ACC •Cluster level, k=1000, uncontrolled, p = 0.089 (trend-significance)
•Lower pre-tx metabolism in Left fusiform/hippo/parahippocamcal gyri •Cluster level, k=1000, uncontrolled, p = 0.004
ACC Left fusiform/hippocamcal gyri
![Page 42: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/42.jpg)
Summary• Medicated M-R MDD patients vs. normal subjects
– Lower metabolism in both L and R DLPFC– Also in the status of limbic-cortical dysregulation
• Patients who responded well to rTMS – Not that severe in limbic-corticol dysregulation– Higher pre-tx ACC and lower left Hippocampal/Fusiform activities
could predict rTMS responses• rTMS mechanism: stimulate L DLPFC
– By reverse metabolism of L DLPFC activities only ?– Might have an effect of normalizing limbal-cortical dysregulation
Responder Non-Responder
![Page 43: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/43.jpg)
Conclusions
Medicated Vulnerable 1st degree
relatives
Target on Enhancing
CREB, BDNF
Balance NT and Frontal-subcortical
circuits
Reduced riskfactors
AntidepressantsrTMSECT
![Page 44: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/44.jpg)
Bipolar disorder雙極性情感性障礙
高潮Mania
低潮
Depression
![Page 45: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/45.jpg)
![Page 46: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/46.jpg)
Manic episode
• Duration: > 4 days - elevated or expansive or irritabe mood
• > 3 sxs or > 4 sxs (if the mood is only irritable)– Grandiosity
– Pressured speech (hypertalkative)
– Flight of ideas (thoughts are racing)
– Distractibility
– Decreased need for sleep
– Hyperactivity (goal-directed) or agitation
– +++ involvement in pleasure activities (spending money, sexual indiscretions and foolish business investment)
• Marked impairment in social activities or occupational functioning and interpersonal relationships
![Page 47: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/47.jpg)
Mixed episode and hypomanic episode
• Mixed episode:– Criteria are met both for manic and depressive episode
– Duration: everyday for > one - week period
• Hypomanic episode:– The criteria is the same as mania
– Disturbance in mood and change in functioning - present
– The episode is not severe enough to cause +++ impairment
in functioning and no psychotic features
• Psychotic mania (mood - congruent and incongruent)
![Page 48: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/48.jpg)
Bipolar Mood DisordersBipolar Mood Disorders
Bipolar I• Defined by mania=mood elevation with impairment
Bipolar II • Defined by major depression PLUS hypomania=mood
elevation, no impairment
Bipolar spectrum • Defined by major depression PLUS minor mood elevation
(mild and/or brief)
Unipolar depression
![Page 49: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/49.jpg)
The Bipolar Spectrum:The Bipolar Spectrum:Bipolar I
4 DaysBipolar II
Bipolar NOS
“Bipolar III” Antidepressant-related hypomania
Adapted from Akiskal HS, Pinto O. Psychiatr Clin North Am. 1999;22:517-534.
< 4 Days
1 week
![Page 50: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/50.jpg)
The Bipolar Spectrum: WeakerThe Bipolar Spectrum: Weaker
Hyperthymic “Bipolar IV”
Depressive Mixed State “IV ½”
Recurrent “Unipolar” Depression “Bipolar V”
Adapted from Akiskal HS, Pinto O. Psychiatr Clin North Am. 1999;22:517-534.Akiskal HS, et al. J Affective Disorders. 2006;96:197-205.
![Page 51: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/51.jpg)
Proportion of Major Depressive Disorder vs Proportion of Major Depressive Disorder vs Bipolar I and II DisorderBipolar I and II Disorder
Angst J, et al. J Affect Disord. 2003;73(1-2):133-146.
49.5%
2.9
Zurich Strict Criteria
25.7%TotalRatio of MDD vsBP I or BP II
9.4
DSM-IV
49.5%
1.0
Zurich Broad Criteria
Bipolar I (BP I)Bipolar II (BP II)Major depressivedisorder (MDD)
HypomaniaMin BPDysthymiaMild depression
5.30%
17.06%
1.65%
20.72% 10.95%
11.41%
0.55%0.55% 0.55%
Major
Minor
![Page 52: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/52.jpg)
Lin Am J Psychiatry 2006; 163:240–246)
Early-onset (age at onset <21)
-higher risks of drug abuse & alcohol abuse
-more rapid cycling and suicide attempts.
![Page 53: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/53.jpg)
Manic/Hypomanic
20%
Mixed13%
Patients with bipolar I disorder experienced mood symptoms nearly half of the time during a 12.8-year follow-up period.
Depressive symptoms were predominant
• Depression was 3.5-fold more frequent than mania
• 90% of patients had at least 1 week of depressive symptoms
• Depression (but not mania) predicted greater future illness burden
Depressed67%
Weeks With
Symptoms47%
Weeks Without
Symptoms53%
Judd et al. Arch Gen Psychiatry. 2002;59:530-537.
Long-term Frequency of Depressive Symptoms (Percentage of Follow-up Weeks)
![Page 54: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/54.jpg)
UnipolarBipolar Polarity Conversion74 initially unipolar, depressed, hospitalized, adolescent/young adult
patients followed for 15 years in the Chicago Follow-up Study
Adapted with permission from Goldberg JF et al. Am J Psychiatry. 2001;158:1265
![Page 55: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/55.jpg)
Differentiating characteristics of bipolar and unipolar depressions
Table 1.3
Bipolar Unipolar
History of mania or Yes Nohypomania (definitional) Sex ratio Equal Women > menAge at onset Teens, 20s, and 30s 30s, 40s, 50sPostpartum episodes More common Less commonOnset of episode Often abrupt More insidiousNumber of episodes Numerous FewerDuration of episodes 3 to 6 months 3 to 12 monthsPsychomotor activity SleepFamily history Bipolar disorder High Low Unipolar disorder High HighPharmacological response Antidepressants
Lithium carbonate Acute antidepressant effect Generally ineffective
Retardation > agitation > Hypersomnia > insomnia
Agitation > retardation > insomnia> Hypersomnia
Induce hypomania / mania
Induction of hypomania / mania is rare
![Page 56: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/56.jpg)
發病原因
•基因缺陷
•腦內神經化學物質分泌異常
•明顯的家族史 ( 情感性疾病 )
•其病程類似癲顯
![Page 57: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/57.jpg)
Bipolar disorder: Etiology
• Genetic defect in MDP involves the circadian pacemaker or systems that modulate it (Goodwin and Jamison 1990)(Goodwin and Jamison 1990) – cycle length with successive episodes– Increased sensitivity to light – Seasonal pattern (some bipolar) – Link between disturbed sleep and mood episodes
• Kindling phenomenon (Post 1992)(Post 1992)
– ““Episodes beget episodes”Episodes beget episodes”– Experience of affective episode (neurotransmitter and peptide
alterations) --- memory trace -- predispose further episodes– Initiate long-term maintenance tx early in the course of illness
![Page 58: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/58.jpg)
Stages of Bipolar Illness Evolution
![Page 59: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/59.jpg)
![Page 60: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/60.jpg)
![Page 61: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/61.jpg)
![Page 62: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/62.jpg)
Neurotrophic Neurotrophic factorsfactors (CREB, BDNF, bcl2, MAP kinase) are targets targets of mood stabilisersmood stabilisers
Atypical antipsychotics eg quetiapine modulate bcl 2, bcl 2, BDNF,BDNF, and BAXBAX
Manji, Bipolar Disord 2003 Wei J Neurosci Res 2003 Luo Brain Res 2004
![Page 63: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/63.jpg)
Neoplasm Cardio-vascular
Cerebro-vascular
Accidents Suicide Other All Causes
29.2*
6.4
1.4* 0.62.2* 1.7 1.6† 1.3 1.6 2.0 2.0* 1.3 2.2* 1.3
* p< 0.001 † p< 0.05
Zurich Cohort, n=4061959-1997
Untreated
Treated
Standardized values- Adapted from Angst, 2000
Living with bipolar disorderMortality ratios: treatment dramatically needed
![Page 64: Mood Disorders Tung-Ping Tom Su, MD Department of Psychiatry National Yang-Ming University Veterans General Hospital-Taipei Sept. 28, 2010 (Yang-Ming IBS](https://reader030.vdocuments.net/reader030/viewer/2022012918/56649d625503460f94a45487/html5/thumbnails/64.jpg)
Thanks for Your attention