Transcript Anxiety and what the psychologists don’t like about it

Anxiety: old data and new theory
Jerusalem May 2004
Matti Mintz
Psychobiology Research Unit
Department of Psychology
Tel Aviv University
http://freud.tau.ac.il/~mintz
[email protected]
In the future, neurology will provide satisfactory
explanation of anxiety (Freud).
The plan:
 Anxiety explained by psychology.
 Anxiety explained by neuroscience.
 Neurobehavioral data extending the present approach
of biological psychiatry toward anxiety.
 Clinical implications.
Normal fear/anxiety explained by Ψ
Aversive event:
Exo/Endogenous
CS/US
Parallel Limbic:
Neocortical/Subneocortical
Evaluation/Conditioning
Coherent response:
Emotional-somatic state
Conscious feeling
Normal fear/anxiety as explained by Φ
Cortex:
slow evaluation
conscious feeling
Amygdala:
rapid evaluation
emotional state
Does anxiety enhance motor conditioning ?
Encounter
with a novel
challenge
Adaptive
fear
response
Fast fear
conditioning
?
Slow motor
conditioning
Non-adaptive
motor
response
Conditioning procedures
EP: Conditioning of fear-CRs (freezing-CRs)
10 paired CS-US trials
CS – 2.8 kHz tone (0.4s, 73 dB)
US – white noise (0.1s, 100dB)
Conditioning of motor-CRs (eyeblink-CRs):
40 paired SC-US trials
CS – 2.8 kHz tone (0.4s, 73 dB)
US – periorbital train (0.1s, 50Hz)
(Neufeld, M. & Mintz, M., 2001)
Amygdala-based fearconditioning enhances
the subsequent
cerebellum-based
motor conditioning
Is amygdala involved in the enhanced
cerebellum-based motor conditioning
Amygdala mediates the
acquisition of
emotional responses,
which subsequently
enhance the
conditioning of
adaptive motor
responses
Is anxiety extinguished after
acquisition of adaptive motor responses?
Encounter
with learned
challenge
Extinction
of fear
response
No fear
response
?
Adaptive
motor plan of
action
Adaptive
motor
response
Fast amygdalabased fear
conditioning
CS-tone
US-airpuff
(Mintz, M. & Wang-Ninio, Y., 2001)
Poor motor conditioning in cerebellar rats
Extinction of fear
after motor
conditioning in
controls but not in
cerebellar rats
Normal individual facing an
aversive challenge
The two stage theory of learning predicts:
1st stage: Fast acquisition of fear responses.
2nd stage: Slow acquisition of motor responses.
Extension to three stage theory of learning:
3rd stage: Extinction of fear responses after acquisition of
motor responses.
Individual with motor disorder facing an
aversive challenge
The three stage theory of learning predicts:
1st stage: Fast acquisition of fear responses.
2nd stage: No/poor acquisition of motor responses.
3rd stage: No extinction of fear responses (anxiety disorder?).
Possible implications for anxiety disorder
Theoretical: In contradiction to the present dogma,
disorders of anxiety may evolve from normal limbic
system that responds persistently due to interaction
with deficient motor system.
Clinical: In contradiction to the present dogma,
motor rehabilitation may ameliorate the anxiety
symptoms.
Comorbidity of balance and anxiety disorders
A special issue of the J. of Anxiety Disorders,
reviewed the experimental and clinical findings
related to comorbidity of balance disorders and
anxiety (Sklare et al., 2001).
Could the comorbidity be explained by the three
stage theory of learning?
Individual with balance disorder
facing balance-challenging conditions
The three stage theory of learning predicts:
1st stage: Fast acquisition of fear responses.
2nd stage: No acquisition of balance restoration motor
responses.
3rd stage: No extinction of fear responses, i.e., anxiety
disorder.
Origin of the comorbidity of balanceanxiety disorders?
Theoretical hypothesis: Anxiety evolves from
normal limbic system that responds excessively and
persistently due to interaction with deficient balance
system.
Clinical implication: Balance rehabilitation may
ameliorate the anxiety symptoms.
The vestibulo-parabrachial network includes connections
between the vestibular nuclei and pathways mediating
anxiety responses (Balaban 2002).
Dominant Hdb mutation of C3HeB/Fej strain with
developmental vestibular stereocilia phenotype
A: SEM demonstrating elongated, abnormal stereocilia in utricle of 5
month old Hdb mouse.
B: Genotyping for presence of Myo7a missense mutation.
Avraham, K. & Hertzano, R.
Hdb vs. wild-type in open-field test
Time in center (sec) - 1 month old
[Interaction: F(19,342)=2.6, p<0.001]
Time in HB (sec) - 1 month old
[Interaction: F(19,342)=2.5, p<0.001]
50
50
45
45
Hdb
Hdb
Wt
Wt
40
40
35
35
30
30
25
25
20
20
15
15
10
10
5
5
0
0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20
Minutes
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20
Minutes
With Schahar Fisher
Hdb vs. wild-type in elevated Plus-Maze test
1 Month Old
Time in Closed Arms (sec)
2 Months Old
Time in Closed Arms (sec)
3 Months Old
Time in Closed Arms (sec)
40
40
40
30
30
30
20
20
20
10
10
10
0
0
1
2
3
4
5
6
7
8
9
10
0
1
2
3
4
5
6
7
8
9
10
1
2
3
4
5
6
7
8
9
10
*
§
35
30
25
no climbing
20
climbing
15
10
5
0
males
%Time spent in the open
arms (sec)
%entries into the open arms
C57/BL6 mice deprived of climbing activity
(P0-P50)
and
tested
ELEVATED
PLUS
MAZE on elevated Plus
OPEN Maze
FIELD TEST
10
no climbing
8
climbing
6
4
2
0
males
females
females
§
1400
Distance moved (cm)
*
§
12
1200
no climbing
1000
climbing
800
600
400
200
0
males
• Climbing
females
effect
§ Gender effect
With Susanna Pietropaolo
Benjamin K. Yee
Joram Feldon
Comorbidity of balance and anxiety disorders
in childhood?
In children with anxiety as primary disorder.
In children with imbalance as primary disorder.
Children with anxiety as primary disorder
Group
Origin
Anxiety
(n=20)
Ambulatory
clinic
Control
(n=20)
Normal class
children
Diagnosis of
anxiety
Age
(yrsSEM)
Gender
(F/M)
Separation (n=11)
Generalized (n=7)
PTSD (n=1)
Phobias (n=1)
10.20.38
(7-14)
8/12
10.60.36
(7-13)
8/12
Erez, O., Gordon, C.R., Sever, J., Sadeh, A. Mintz, M. 2004.
Children with anxiety disorders vs. controls:
 Reported more dizziness episodes (80 vs. 40%).
 Reported enhanced sensitivity to motion sickness
provoking situations.
 Were hypersensitive to the rotary chair test.
Children with anxiety disorders had more
balance mistakes relative to controls
Test
Manipulation effect
Group
effect
Interaction
G by M
Stand
heel-to-toe
Floor-bench
Eyes open-closed
ns
**
ns
ns
ns
Stand on
one-foot
Floor-bench-trampoline
Eyes open-closed
***
***
ns
*
ns
Stand on
cylinder
Head still-nodding
*
*
ns
Walk on
cubicles
Eyes open-closed
***
ns
ns
Walk on
rope
Normal-heel-to-toe
Eyes open-closed
***
***
*
ns
*
*p<0.05;
**p<0.01; ***p<0.001
Children with imbalance as primary disorder
N ♂/♀
Clinical Referred to OT
for balance
treatment
Control Normal class
children
Age
Age
(yrs±SE range
(yrs)
M
35 26/9 5.8±0.10 5.0-7.3
25 15/10 5.8±0.15 5.0-7.3
With Meidan, M., Sadeh, A., Brat, O.
Relation between parental report on balance
and self-reported emotionality
Vestibular Scale (Dunn)
60
Clinical
50
Control
r=-.32
40
30
20
r=-.52*
10
0
10
20
Anxiety - Depression (CBCL)
30
Relation between balance performance and
parental report on emotionality
Balance (Bruninks)
30
Clinical
25
Control
r=.03
20
15
10
r=-.72*
5
0
0
10
20
Anxiety - Depression (CBCL)
30
Balance rehabilitation in children with
imbalance as primary disorder
N ♂/♀
Age
Age
(yrs±SE range
(yrs)
M
25 22/3 5.4±0.08 5.0-6.1
Treated Referred to OT
for balance
treatment
24 21/3 5.4±0.09 5.0-6.1
Waiting list of
Nontreated similarly
referred children
With Weisman, E., Bar-Haim, Y., Brat, O.
‫דוגמא של אימון בערסל‪:‬‬
Balance test (Bruninks-Oseretsky)
Treatment
15
15
14
14
13
13
12
12
11
11
10
10
9
9
8
8
7
7
6
6
5
5
4
Control
O
O
O
4
3
3
2
2
1
1
O
0
Before treatment
After treatment
Group by Time: p<.001
Anxiety level
Fear Survey: Child Report
O
O
O
15
0
150
100
100
50
50
0
0
Gr x Treatment: p<.001
O
CBCL: Parental reports
O
15.00
O
10.00
10.00
Gr x Treatment: p<.001
O
15.00
5.00
5.00
0.00
0.00
Before treatment
O
After treatment
Treatment
Control
Conclusions concerning the origin of
anxiety disorders
The prevailing view in biological psychiatry is that
disorders of anxiety are the product of structural or
functional pathology of the limbic system.
The present hypothesis suggests that anxiety may be
precipitated by extralimbic sensory-motor dysfunctions,
in spite of normal limbic system.
Clinical implications: we consider the physical
treatment of anxiety as an alternative to the present
practice of pharmacological and psychological
approach.
‫(תגובה לכתבה 'כח המח' במוסף הארץ)‬
‫שלום‬
‫אני בן ‪ 29‬שסובל מחרדת קהל (ומדי פעם מחרדה כללית)‪ .‬רציתי‬
‫להגיד לכם שעליתם על משהו מהפכני! כאשר אני עומד לאבד את‬
‫שיווי המשקל (נגיד להחליק) או כאשר אומרים לי לדבר בפני קהל‬
‫ההרגשה זהה‪ .‬ולכן אני חושב שזאת אותה מערכת משוב במח עבור‬
‫חרדה כלשהי ואיבוד שיווי משקל‪.‬‬
‫הסבר ‪ :‬למצב של הרגשת איבוד שיווי משקל עם הקטנוע אני לא‬
‫מוכן להגיע (מסוכן) ולכן מצבי החרדתי לא משתפר‪ .‬חיפשתי משהו‬
‫שיגרום לי להרגיש את תחושת איבוד שיווי המשקל החריפה אך לא‬
‫יהיה מסוכן מדי והתחלתי ללכת על דופן האמבטיה‪ .‬נוצר שיפור‬
‫מסוים ברמת החרדה אך הרגשת איבוד שיווי המשקל למצב זה‬
‫חלפה ועל מנת להמשיך בשיפור אני אצטרך למצוא משהו מסוכן‬
‫יותר‪ .‬לפי דעתי אם תפתחו שיטות בטוחות לאימון שיווי משקל עם‬
‫רמת קושי עולה יהיה אפשר להתגבר על חרדות חזקות מכל‬
‫הסוגים‪.‬‬
‫מקווה שהייתי מובן ולעזר‬
‫בהצלחה אמיר‬
End of presentation
Auditory CS
pathways
Bottom-up implementation of anatomy
Balance tests:
Balance sub-test of the Bruninks-Oseretsky
Test of Motor Proficiency (Bruninks, 1978).
Vestibular scale of The Parental Sensory Profile
Assessment (Dunn, 1999).
Anxiety tests:
Anxiety-Depression Parental Scale of the Child
Behavior Checklist (CBCL; Achenbach, 1991).
Fear Survey Schedule for Children – self report
(FSSC; Ollendick, 1983).
Emotion and feeling


Emotion = bodily state mediated by subcortical &
peripheral autonomic, endocrine & skeletomotor res.
Feeling = conscious sensation mediated by cingulate &
frontal cortex.
Stimulus
Expansion of the
limbic system
MacLean expanded the
limbic system to include
the septum, accumbens,
amygdala, orbitofrontal
cortex.
Amygdala and not the
hippocampus coordinates
the activity of the
hypothalamus with the
cortex.
Amygdala, rather than Papez’s hippocampus
Conscious feeling:
Cingulate cortex
Parahippocampal
Prefrontal
Amygdala
Somatic emotion:
Hypothalamus
Brainstem nuclei
Electrical stim of human amygdala → triggers feeling and
somatic expression of fear.
Calcification of human amygdala (Urbach-Wiethe disease) →
disrupts implicit processing of facial cues of fear but does
not impair explicit recognition of faces/objects.
Amygdala mediates acquired
emotional responses
18.5.04 Studied in context of classical conditioning: CS – US association
and contingency (predictability).
Amygdala→ Rapid Res.
Tone CS→ Brainstem→ Thalamus
Cortex→ Amygdala→ Slow Res.
Somatosensory US→ Brainstem→ Thalamus→ Amygdala→ Rapid Res.
Output of the central n. through the stria terminalis
& v. amygdalofugal pathway