dysautonomic symptoms and major depression. 自律神經失調 (dysautonomia)...

Dysautonomic symptoms and major depression

自律神經失調 (Dysautonomia)

• 口乾、口渴、口內疼痛、口舌異常感、味覺異常、缺乏食慾；耳鳴、耳阻塞感等。

• 姿勢性低血壓，頭暈，眼前發黑，甚至暈倒。• 尿失禁、頻尿，性功能障礙• 多汗• 呼吸困難、心悸，胸悶，胸部壓迫等。• 焦躁易怒、集中力及記憶力減弱、不安等等。全

身乏力，失眠等毛病。

• Depressed mood• Feelings of guilt• Suicide attempt• Insomnia- early• Insomnia- middle• Insomnia- late• Loss of interest • Retardation• Anxious behavior

Hamilton Depression Rating Scale

• Worrying• Hypochondriasis • Somatic anxiety• Appetite• Libido• Lethargy & fatigue• Body weight loss• Lack of insight

• depressed mood• feelings of guilt• suicide• insomnia- early• Insomnia- middle• Insomnia- late• interest and activities• retardation• agitation• psychic anxiety• somatic anxiety• general somatism• genital symptoms• hypochondriasis • body weight loss• insight

Psychic anxiety

Sleep disturbance

Somatic anxiety

Depressed mood

Component disturbance of a depressed mood

HAM-D

Hong CJ, Oct 2006

1. Anxious mood • worries • anticipates worst

2. Tension • startles • cries easily • restless • trembling

3. Fears • fear of the dark • fear of strangers • fear of being alone • fear of animal

4. Insomnia • difficulty falling asleep • nightmares

5. Intellectual • poor concentration • memory impairment

6. Depressed Mood • decreased interest in activities • anhedonia

7. Muscular complaints • muscle aches or pains • bruxism

8. Sensory complaints • tinnitus • blurred vision

Hamilton Anxiety Rating Scale

9. Cardiovascular Symptoms • tachycardia • palpitations • chest pain • sensory of feeling faint

10. Respiratory Symptoms • chest pressure • choking sensation • shortness of breath

11. Gastrointestinal Symptoms • dysphagia • nausea or vomiting • constipation • weight loss

12. Genitourinary Symptoms • urinary frequency or urgency • dysmenorrhea • impotence

13. Autonomic Symptoms • dry mouth • flushing • pallor • sweating

14. Behavior at Interview • fidgets • tremor • paces

Hamilton Anxiety Rating Scale

Milestones of Psychiatry

1950‘s

1980‘s

Schizophrenia Depression

clozapine fluoxetine

chlorpromazine imipramine

Hong CJ, Dec 1999

Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region

Lesch KP: Science.1996

a self-report inventory based on the five-factor model of personality

Molecular Psychiatry 2002 July

Changes in Autonomic Reactivity?

Human• Depression/Anxiety• Antidepressant treatments• Anticholinergics in depression

and dementia• PS1 mutation dementia• Postpartum depression

Animal• Helplessness/Anxiety• Antidepressant treatments• Anticholinergics in depressi

on and dementia• PS1 mutation mice• Infanticidal mother mice

Inescapable/uncontrollable shock (Seligman & Maier, 1971; Anisman 1979)

Helplessness Training & Escape Test

PsyLab 2002/04/04

Video

Video

Fig.2. Five of the 8 C57 male mice remained helpless 10 days after the stress protocol of intermittent conditioning inescapable minor foot-shock.

Non-helpless

Helpless

Figure 6. GRPR-Deficient Mice Have Enhanced and Resistant Long-Term But Not Short-Term Amygdala-Dependent Fear Memory

Potential antidepressant effect of PX01 was demonstrated in FST and TST

Locomotion

0500

10001500200025003000350040004500

Group

Am

bula

tory

Dis

tance (cm

)

control

cysteamine50mg/kg

cysteamine100mg/kg

cysteamine200mg/kg

imipramime10mg/kg

＊＊

＊

Figure 3. The ambulatory distance in 5min locomotion test (n=5 for each group). Mice receiving cysteamine administration have significant reductions in the locomotion activities(p<0.05).

Injection locomotion TST FST

20min

rest

5 min 5 min

rest

6 min 14min

rest

6 min

2007/01/19

Tail Suspension Test (TST)

0

50

100

150

200

250

Group

Mobili

ty (s) control

cysteamine50mg/kg

cysteamine100mg/kg

cysteamine200mg/kg

imipramime10mg/kg

Figure 4. The mobility time in 6min tail suspension test. There are no differences between groups receiving vehicle and drugs (control, n=5; cysteamine50mg/kg, n=5, p=0.149; cysteamine100mg/kg, n=4, p=0.816; cysteamine 200mg/kg, n=5, p=0.179; imipramine10mg/kg, n=4, p=0.258).


20min

rest

5 min 5 min

rest

6 min 14min

rest

6 min

2007/01/19

Forced Swimming Test (FST)

0

20

40

60

80

100

120

140

contr

ol

cyste

amine

50mg/k

g

cyste

amine

100m

g/kg

cyste

amine

200m

g/kg

imipr

amim

e10m

g/kg

Group

Mob

ility

(s)

control

cysteamine50mg/kg

cysteamine100mg/kg

cysteamine200mg/kg

imipramime10mg/kg

Figure 5. The mobility time in 6min Forced swimming test. There are no differences between groups receiving vehicle and drugs (control, n=5; cysteamine50mg/kg, n=5, p=1.000; cysteamine100mg/kg, n=5, p=0.497; cysteamine 200mg/kg, n=5, p=0.052; imipramine10mg/kg, n=5, p=0.983).


20min

rest

5 min 5 min

rest

6 min 14min

rest

6 min

2007/01/19

Dementia and Autonomic Reactivity

• Acetylcholine deficiency is an important pathophysiology of dementia

• Acetylcholine is the key neurotransmitter of parasympathetic nervous system

• Anticholinergic agents are bad for memory but good for mood

Archive of General PsychiatryOct 2006

Dominant Inheritance

ENU-mutagenized mice displaying waddling behavior were linked to Chr.18

151MB6,♂ waddlingBALBNormal BALB, ♀

F1

F2

PsyLab 2006 Dec

(video)

(video)

(video)

Rough mapping

Four of five (80%) waddling mother mice did not nurse their pups

The only one nursing mother killed all of her five pups at age 2 weeks.

Functional and Micro-Magnetic Resonance Imaging Center

DWI_SE_BIO

TR=1500 ms TE=32 ms Slth=1 mm FOV=2 cm

NEX=4 SW=41666.6 Hz Big delta=15 ms Matrix =256*192 b=1100 s/mm2

controlwaddling

Lt Entorhinal cortex Lt Entorhinal cortex

Lat ventricleLat ventricle

Functional and Micro-Magnetic Resonance Imaging Center

DWI_SE_BIO

TR=1500 ms TE=32 ms Slth=1 mm FOV=2 cm

NEX=4 SW=41666.6 Hz Big delta=15 ms Matrix =256*192 b=1100 s/mm2

controlwaddlingLat ventricle Lat ventricle

Dysautonomia的原因

• 長期壓力• 細菌病毒感染• 中風、心肌梗等• 更年期荷爾蒙異常• 遺傳或基因突變

• The prevalence of autonomic symptoms in dementia and their association with physical activity, activities of daily living and quality of life.Dement Geriatr Cogn Disord. 2006;22(3):230-7. Epub 2006 Aug 10.

• Acute dysautonomia following mumps.Neurol India. 1999 Jun;47(2):130-2. Review.

• Depression, the autonomic nervous system, and coronary heart disease.Psychosom Med. 2005 May-Jun;67 Suppl 1:S29-33. Review.

• Depression in patients with acute myocardial infarction: influence on autonomic nervous system and prognostic role. Results of a five-year follow-up study.Int J Cardiol. 2007 Jan 31;115(1):46-51. Epub 2006 Jun 22.

• Increased systemic catecholamines in complex regional pain syndrome and relationship to psychological factors: a pilot study.Anesth Analg. 2004 Nov;99(5):1478-85; table of contents.

• A functional-structural model to understand cardiac autonomic nervous system (ANS) dysregulation in affective illness and to elucidate the ANS effects of antidepressive treatment.Eur J Med Res. 2004 Jan 26;9(1):37-50. Review.

Dysautonomia in dogsDysuria 11/11

Distended urinary bladder 10/10

Mydriasis 11/11

Absent pupillary light reflex 11/11

Dry mucous membranes 10/11

Weight loss 8/10

Decreased Schirmer tear test (<15 mm/min) 8/10

Decreased anal reflex 7/9

Decreased appetite 7/10

Vomiting/Regurgitation 6/9

Lethargy 7/11

Elevated third eyelid 5/11

Constipation 3/9

Dysphagia 3/9

Diarrhea 3/9

Weakness 2/9

Abdominal pain 1/10

Diagnostic Criteria for Major Depression• Depressed mood• Markedly diminished interest or pleasure• More than 5% body weight loss or gain in a month• Insomnia or hypersomnia• Psychomotor agitation or retardation• Fatigue or loss of energy, feeling of worthlessness or guilt• Diminished ability to think, concentrate• Recurrent thoughts of death# Five of above symptoms appear most of the day, nearly every day fo

r at least 2 weeks and cause a significant change from previous functioning.

Diagnostic Criteria for Major Depressive Episode

Montgomery-Asberg Depression Rating Scale

(1) apparent sadness(2) reported sadness(3) inner tension(4) reduced sleep(5) reduced appetite(6) concentration difficulties(7) lassitude(8) inability to feel(9) pessimistic thoughts(10) suicidal thoughts

SOMATIC ANXIETY (Tachycardia, palpitations, chest pain, choking feeling, sighing, dyspnea, hyperventilation, dry mouth, difficulty swallowing, flatulence, gastric pain, nausea, vomiting, diarrhoea, constipation, urinary frequency, sweating, giddiness, blurred vision or tinnitus)

The ANS controls• Cardiovascular system• Digestive system• Respiratory functions• Salivation• Perspiration• Pupils • Micturition• Erection

Am J Hum Genet. 2001 March; 68(3): 753–758.

Familial Dysautonomia Is Caused by Mutations of the IKAP Gene

Sylvia L. Anderson,1 Rocco Coli,1 Ira W. Daly,1 Elizabeth A. Kichula,1 Matthew J. Rork,1 Sabrina A. Volpi,1 Josef Ekstein,2 and Berish Y. Rubin1

1Department of Biological Sciences, Fordham University, Bronx, NY; and 2Dor Yeshorim, The Committee for Prevention of Jewish Diseases, Brooklyn, NY/Jerusalem

• Orthostatic hypotension - extreme drop in blood pressure with change in posture

• Breath holding in early years to the point of fainting • Episodic vomiting • Excessive drooling and sweating • A smooth tongue and decrease in sense of taste • Inappropriate temperature control with very high to very low tem

peratures • Poor weight gain and growth • Decreased reaction to pain or no reaction at all • Cold, puffy hands and feet • Extremes in blood pressure • Corneal abrasions and dry eyes • Gastric dysmotility • Dysautonomic "crisis"

Symptoms in an older child with familial dysautonomia

Autonomic nervous system controls• Cardiovascular system• Digestive system• Respiratory functions• Salivation• Perspiration• Pupils • Micturition• Erection

Antidepressants in Depression and Anxiety

• The serotonergic system has been implicated in the alterations in appetite, energy, sleep, mood, libido, and cognitive functioning seen in anxiety and affective disorders.

Mitral valve prolapse and dysautonomia

• Fatigue • Chest pain• Palpitations or irregular heart beat • Migraine headaches• Anxiety• Depression• Panic attacks• Shortness of breath

dysautonomic symptoms and major depression. 自律神經失調 (dysautonomia)...

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