neural substrate for mental illness tung-ping su department of psychiatry national yang-ming...
Post on 23-Jan-2016
220 views
TRANSCRIPT
![Page 1: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/1.jpg)
Neural substrate for mental illnessTung-Ping Su
Department of PsychiatryNational Yang-Ming University
Taipei Veterans General Hospital
Nov.14, 2006 at Brain Institute, NYMC
![Page 2: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/2.jpg)
![Page 3: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/3.jpg)
![Page 4: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/4.jpg)
![Page 5: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/5.jpg)
![Page 6: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/6.jpg)
![Page 7: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/7.jpg)
![Page 8: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/8.jpg)
Dopaminergic pathway
![Page 9: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/9.jpg)
Noradrenergic pathway
![Page 10: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/10.jpg)
Serotonergic pathway
![Page 11: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/11.jpg)
![Page 12: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/12.jpg)
精神疾病之主要分類精神疾病之主要分類精神疾病
重型疾病 輕型疾病
精神分裂症情感性精神症 身體化症
泛焦慮症
創傷後症候群
強迫症
社交畏懼症
恐慌症
輕鬱症躁
鬱症
重鬱症
老人失智症與
其他精神疾病
兒童青少年
精神疾病
人格疾患
器質性腦症候群
藥物、酒精濫用
![Page 13: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/13.jpg)
Pathogenesis: worry and anxiety
Culpepper explained: anxiety expressed through high cortical activity, which can be activated by sudden noise or memories---stimulate other portions of brain --- SxsJ Clin Psychiat 2004
Chrousos JAMA 1992Chrousos JAMA 1992
![Page 14: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/14.jpg)
The Brain Circuits of GAD:Overactive fronto-cortical-basal gangalial loop
David J Nutt2000
• OCD:OrbitofrontalFC -- BG• GAD:Rostral partsFC --BG
![Page 15: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/15.jpg)
Integrating neurochemistry and brain circuits of GAD
D J Nutt2000
![Page 16: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/16.jpg)
Neuroimaging studies in GNeuroimaging studies in GADAD
![Page 17: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/17.jpg)
Benzodiazepine Benzodiazepine receptorsreceptors in in GADGAD
Controls(grand average)
GAD patients(grand average)
Decreased BDZ receptor binding of [123I]NNC 13-8241 in left temporal pole ofGAD patients indicates less homogeneous receptor density distribution
Tiihonen et al, 1997
![Page 18: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/18.jpg)
![Page 19: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/19.jpg)
Neuroimaging of
Panic Disorder
![Page 20: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/20.jpg)
![Page 21: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/21.jpg)
Neuroanatomy of Panic DisorderImplication of functional imaging in fear conditioning
Pathway of viscerosensory information in the brainPathway of viscerosensory information in the brain
BP, HRvia NE release
Respiratory rate
cortisol
PAG: defensive B,Pain modulation
Contextual & cueFear conditioning
Memory processing Direct mode
Fast circuit
Indirect modeSlow circuit
![Page 22: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/22.jpg)
Neurocircuitry of PD
Fast mode bottom-up
Slow mode, top-down
![Page 23: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/23.jpg)
Efferent pathways from amygdalato elicit autonomic symptoms and neuroendocrino
logy
PAGPAG LCLC
PBNPBNHPA axisHPA axis
Hypothalamus
pituitary
![Page 24: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/24.jpg)
![Page 25: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/25.jpg)
Amygdala
Hippocampus
Temporal lobe
T1 weighted imageT1 weighted image
Amygdalar atrophy in panic disorder patients (VMRI) Massana G et al.: NeuroImage 19 (2003) 80–90
SmallerLt 23.4%Rt 31.9%
PD vs. CRL
NS for bothsides
NS for bothsides
![Page 26: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/26.jpg)
Voxel-based morphometry of gray matter utilizing Jacobian modulation: 10 panic disorder patients versus 23 normal controls p < 0.001) (right=right, left=left),
• Increased gray matter vol. in the dorsal and ventral midbrain and rostral pons of the brainstem. (bottom-up)
• Increased left ventral hippocampal, right occipital and right middle temporal volumes.
• Decreased regional prefrontal cortex volumes (top-down)
Protopopescu X et al, Neuroreport, 2003
![Page 27: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/27.jpg)
5-HTT binding in the midbrain of a control subject (A) and a patient with current PD (B). 5-HTT—serotonin transporter, PD—panic disorder Maron E et al 2004, Psychiatric research neuroimaging;132:173-181
Reduced brain 5-HTT binding in patients with panic disorder
• Decrease in 5-HTT binding in the midbrain, temporal lobes and thalamus vs. the control.
• The PD in remission was similar to CRL in the midbrain and in the temporal lobes, but lower in the thalamus (trait marker)(trait marker) (5-HTT binding).
• Regional 5-HTT binding negatively correlated with the severity of panic symptoms.
Remission is with normalization of 5-HTT binding.
• Deficit in brain 5-HT ---panic or reflect a compensatory Process in 5-HT system?
![Page 28: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/28.jpg)
Middle brain (12 mm above the anterior commisure–posterior commisure plane) median volume of distribution map for controls (left) and patients with panic disorder (right). Note the generalized decreasedecrease in volume of distribution affecting the thalamithalami and the heads of the caudate nucleuscaudate nucleus. PD may be due to defective brain inhibition--- allow paroxysmal elevations of anxiety during panic attacks.
Decreased brain GABAA-Benzodiazepine receptor binding by C11flumazenil in PD, Malizia AL et al.: Arch Gen Psychiatry 55(1998) 715–720
Orbito-frontal
Insula
thalamus
Caudate
![Page 29: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/29.jpg)
China TaipeiSARS,2003
Kao-ShungSARS, 2003
Nan-TouEpicenter of 921 EQ 1999
Su, 2005
![Page 30: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/30.jpg)
Symptoms of PTSD
Overwhelming trauma
1. Reexperience of traumatic
events (flashback)
2. Startling response
3. Avoidance
![Page 31: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/31.jpg)
Results and Discussion
Emotional Stroop Task
PTSD, p<0.01
![Page 32: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/32.jpg)
Results and Discussion
Classical Conditioning for PTSD
Patient, p<0.05
![Page 33: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/33.jpg)
![Page 34: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/34.jpg)
![Page 35: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/35.jpg)
1H-MR spectrum from human brain1H-MR spectrum from human brain
![Page 36: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/36.jpg)
1652718-7 Tsai
0.95
1.08
2001 2003
1.22
NAACho Cr Cho Cr
NAA
1.17Cho Cr
NAA
NAA
CrCho
![Page 37: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/37.jpg)
0.8
1
1.2
1.4
1.6
1.8
2
NAA
/ Cr
0.8
1
1.2
1.4
1.6
1.8
2
NA
A /
Cr
Comparison of NAA/Cr ratio of bilateral hippocampus Comparison of NAA/Cr ratio of bilateral hippocampus PTSD (n = 11) vs. Taipei controls (n = 13) in 2001PTSD (n = 11) vs. Taipei controls (n = 13) in 2001
Left hippocampus Right hippocampus
*
TPE-CTL TPE-CTL PTSD PTSD
(*: P<0.05 )
![Page 38: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/38.jpg)
![Page 39: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/39.jpg)
Response to stress in normal, major depression and PTSD
![Page 40: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/40.jpg)
Hypothesis for disaster-related PTSD
Overwhelming stress
HPA axis
• Memory, attention and emotion impairment: Lower NAA/Cr (Lt. hippocampus) Poorer neurocognitive function Low basal cortisol
DST dysregulation
![Page 41: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/41.jpg)
Affective DisordersAffective Disorders
Tung-Ping Tom Su, MDTung-Ping Tom Su, MD
Department of PsychiatryDepartment of Psychiatry
Veterans General Hospital-TaipeiVeterans General Hospital-Taipei
National Yang-Ming UniversityNational Yang-Ming University
![Page 42: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/42.jpg)
Cerebral glucose metabolism: PET study
![Page 43: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/43.jpg)
![Page 44: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/44.jpg)
A Little Science FictionA Little Science Fiction
Atrophic“depressed”
“Treated”
![Page 45: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/45.jpg)
![Page 46: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/46.jpg)
![Page 47: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/47.jpg)
![Page 48: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/48.jpg)
PET–Impaired PerfusionPET–Impaired Perfusion
Drevets WC, et al. Nature. 1997;386(6627):824-827.
X=-3
Y=31
Subgenual PFC
-5.5 -2.5 0I-Value
![Page 49: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/49.jpg)
![Page 50: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/50.jpg)
![Page 51: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/51.jpg)
fMRI responses in patients with depression
• Caudate activation as a correlate of intrinsic learning
• Reduced activation in older patients with depression
• Future of psychological probes and fMRI in patients with post-infective fatigue states
![Page 52: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/52.jpg)
4.8
5
5.2
5.4
5.6
5.8
6
6.2
6.4
6.6
Control Early Onset Late Onset
Aetiological Group
Hipp
ocam
pal V
olum
e (m
m3)
![Page 53: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/53.jpg)
![Page 54: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/54.jpg)
![Page 55: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/55.jpg)
![Page 56: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/56.jpg)
![Page 57: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/57.jpg)
Depression: imaging finding
Depression: 1. increase BF/GMR of medical orbital , VMPFCor amygdala, or pregenual ant. Cingulate2. Decrease DLPFC and subgenual portion of ant. cingulate
![Page 58: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/58.jpg)
Frontal-subcortical circuit
governance
• Lt frontal: positive emotion
• Rt frontal: negative emotion
Acute depression (transient sadness)Lt PFC activity increase
Chronic depressionLt PFC activity decrease
• Similar to seizure:
Cingulate:Attention& mood
Amygdala:Emotional recognition of facesLt Amygdala activated during sadness
• Personality change
![Page 59: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/59.jpg)
New Concept of Treatment New Concept of Treatment in Psychiatric Disorders: in Psychiatric Disorders:
• TMSTMS
• VNSVNS
• DBSDBS
![Page 60: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/60.jpg)
![Page 61: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/61.jpg)
![Page 62: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/62.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 63: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/63.jpg)
• ResultsResults
Hamilton Depressive Rating Scale
0
5
10
15
20
25
30
35
40
Baseline 1st week 2nd week 3rd week 4th week
Time
Open Trial of rTMS, Huang & Su: European Psychiatry 19 (2004) 523-524
![Page 64: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/64.jpg)
躁鬱症
雙極性情感性障礙
高潮
低潮
![Page 65: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/65.jpg)
![Page 66: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/66.jpg)
![Page 67: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/67.jpg)
![Page 68: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/68.jpg)
![Page 69: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/69.jpg)
![Page 70: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/70.jpg)
![Page 71: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/71.jpg)
![Page 72: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/72.jpg)
![Page 73: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/73.jpg)
![Page 74: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/74.jpg)
![Page 75: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/75.jpg)
![Page 76: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/76.jpg)
![Page 77: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/77.jpg)
![Page 78: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/78.jpg)
The dopamine system
Stahl SM. Psychopharmacology of Antipsychotics. 1st ed. 1999.
![Page 79: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/79.jpg)
![Page 80: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/80.jpg)
![Page 81: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/81.jpg)
![Page 82: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/82.jpg)
Developmental dysregulation of the dopamine sysDevelopmental dysregulation of the dopamine system and the pathophysiology of schizophreniatem and the pathophysiology of schizophrenia
Prefrontal cortex
Amyg-dala
HypothalamusHPA axis
Ventralhippocampus
LC
StressStress1.1. Genetic: diffuse subtle Genetic: diffuse subtle
changes in PFCchanges in PFC
suppressionsuppression
VTAVTA
DA: hyper-activatedto stress
SCZ: pathology in cortico-limbic circuit:2. abnormal striatal DA2. abnormal striatal DA
•Delayed onset ofSCZ: delayed delayed pathology (damage)pathology (damage) in hippocampusin hippocampus(interaction of (interaction of stress vs. stress vs. hippocampus basedhippocampus basedon PFC disruptionon PFC disruption))
Mesocorticalpathway
Su TP, 2005Su TP, 2005
Increased release of glucocorticoids under stress
damagedamage
![Page 83: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/83.jpg)
![Page 84: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/84.jpg)
In-vivo Mapping of Fiber Pathways in
Schizophrenia
Using Diffusion Tensor MRI
Tung-Ping Su, MD, Yuan – Hwa Chou, MD, PhD Ya-Mei Bai, MD, PhD, Kun-Hsien Chou, Fang-Ying Chiu, Chin-Po Lin, PhD
Brain Function and Imaging LaboratoryDepartment of Psychiatry, TVGH & NYMUInstitute of Neuroscience, NYMU
![Page 85: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/85.jpg)
![Page 86: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/86.jpg)
x
Water diffusion behavior
• Diffusion Weight Image (DWI)
• Diffusion Tensor Imaging
• Q-ball, DSI
Image Lab and Brain connectivity Lab, NYMU, Taiwan
![Page 87: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/87.jpg)
Diffusion Tensor Imaging (DTI)
Basser et al. (Biophys J 1994)
Dxx Dxy Dxz
Dyx Dyy Dyz
Dzx Dzy Dzz
x
y
z
x
y
z
xx
yy
zz
yz
xy
xz
1st eigenvector field
Normalize
13
12
11
1
13
12
11
E
E
E
E
E
E
DzzDzyDzx
DyzDyyDyz
DxzDxyDxx
![Page 88: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/88.jpg)
Tractography – FACT algorithm
Image Lab and Brain connectivity Lab, NYMU, Taiwan
Short arrows represent vector directions of the largest principal axis.
A tracking (a long arrow) is started from a center of a selected voxel and
a line is propagated by observing the vector direction of each voxel
( Fiber Assignment by Continuous Tracking )
![Page 89: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/89.jpg)
Normal control > Schizophrenia subjects
Cluster size
Coordinates of the most significant voxel T-score Anatomical location
Voxels x y z R/L 984 -6 6 20 4.93 L Corpus callosum424 42 -2 24 4.44 R Frontal sub-gyral WM175 32 -66 18 3.93 R Middle temporal gyrus WM
92 30 20 20 3.54 R Frontal sub-gyral WM
89 32 42 2 3.49 R Frontal sub-gyral WM72 12 -24 -22 3.16 R Brain stem
60 -36 0 38 2.97 L Middle frontal WM, BA 6
49 20 -32 28 3.16 R Corpus callosumStatistical criteria: p-value < 0.01, cluster > 48 voxels
Normal volunteers : 36 healthy subjects, 23 F and 13 M, 42.73 ± 11.19 y/oSchizophrenia : 18 patients, 12 F and 6 M, 41.36 ± 9.64 y/o
Schizophrenia Study
![Page 90: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/90.jpg)
Normal > Schizophrenia subjects
Result (I) : Compare Normal Volunteers to Schizophrenia
![Page 91: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/91.jpg)
偵測過動兒症及雙極性情感症疾患之腦部白質的異常
擴散張量造影(Diffusion Tensor Imaging)
![Page 92: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/92.jpg)
Decreased FA values of the brain areas
in the comparison among controls, bipolar & unipolar
![Page 93: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/93.jpg)
Normal > BD
![Page 94: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/94.jpg)
![Page 95: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/95.jpg)
MDD > BD
![Page 96: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/96.jpg)
Ventral
Ventralstriatum
Orbitofrontalcortex
Thalamus(MD)
AnteriorCingulate(SGPFC)
Expression of BipolarDisorder
Amygdala
Cerebellarvermis
Hypothalamua
‘Cognitive’ cortical areas(e.g., DLPFC)
A BAnterior limbic network
![Page 97: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/97.jpg)
JoBuat 6 months old
![Page 98: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/98.jpg)
1 yrs old
![Page 99: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/99.jpg)
1 yrs old
![Page 100: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/100.jpg)
16 months old
![Page 101: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/101.jpg)
![Page 102: Neural substrate for mental illness Tung-Ping Su Department of Psychiatry National Yang-Ming University Taipei Veterans General Hospital Nov.14, 2006 at](https://reader036.vdocuments.site/reader036/viewer/2022062410/56649d575503460f94a353a8/html5/thumbnails/102.jpg)
Thanks for your attention !