To approach or to avoid : neurobiological mechanisms in social anxiety Peer, J.M. van
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(2) Chapter 3. Hypothalamus-Pituitary-Adrenal axis hyperresponsiveness is associated with increased social avoidance behavior in social phobia. ȋʹͲͲͻȌǡͷǡ͵͵Ǧ͵Ͷ͵ǡ ǣͳͲǤͳͲͳȀǤ ǤʹͲͲͺǤͲͺǤͲʹʹ Ǥǡ ǤǤǡǤǡǤ ǡǤǡƬǤǤ.
(3) Chapter3. Abstract Background ǦǤ
(4) ǡ Ǧ Ǥ Ǧ ȋȌǤ Methods ȋnαͳͺȌǡ ȋnαʹʹȌ ȋǣnαͳȌǡ ǡ Ǧ ȋǦȌ ȋ ȌǤ Ǧ Ǧ ǡ ȋ ȌǤ ǡ Ǥ Results ǡ Ǥ ǡ Ǧ Ǥ Ǧ Ǥ Conclusions Ǧ Ǥ Ǥ. Ͷͺ.
(5) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia. Introduction ȋȌ ȋ Ƭ Úǡ ʹͲͲǢ Ǥǡ ͳͻͻͷȌǤ ǡ ǡ ȋƬ ǡͳͻͻͷǢǡ ǡƬ ǦǡʹͲͲȌǤ ǡ Ǥ . . ǦǦ ȋ ȌǦǡ ǡ ȋǡ ͳͻͻͲȌǤ ǡ Ǧ ȋǤǡͳͻͻͺǢǡ ͳͻͻͲȌǤ ǡ ǡ ȋ Ǥǡ ʹͲͲǢ ǡ ǡ ǡ ǡ Ƭ Ǧǡ ͳͻͻȌǤ Ǧ ȋǤǡʹͲͲͷǢǡǡ ǡǡƬ ǡʹͲͲǢ ǤǡͳͻͻͺǡʹͲͲͲȌǤ ǡ Ǧ Ǧ Ǧ Ǥ ȋ Ǥǡ ʹͲͲʹȌǡ ȋ ǤǡʹͲͲͳǢǤǡͳͻͻ͵ǢǤǡͳͻͻͻȌǤǡ ǡ Ǥ ȋ Ƭ ǡʹͲͲȌǤ . Ǧ ȋǦȌ ȋ Ƭ ǡ ʹͲͲͶȌ . . Ͷͻ.
(6) Chapter3. ȋ ǡ ǡ Ƭ ǡ ʹͲͲǢ Ǥǡ ʹͲͲͷǢ Ǥǡ ʹͲͲȌǤ ȋȌ ǡ Ǧ Ǥ ǡ ǡȋ ǤǡʹͲͲǢǤǡʹͲͲʹǢǤǡʹͲͲͶȌǤ Ǧ Ǥ ǡ ȋ ǡ Ȍ ǡ Ǥ Ǧ ǡ ȋǣ Ǥǡ ͳͻͻ͵ȌǤ Ǧ ǡ Ǥ ǡ Ǧ Ǥ. MethodsandMaterials Participants Ǧ ͵ǤͳǤ
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(9) ȋ
(10) ǦȀǣ ǡ ǡ. ǡ Ƭ ǡ ͳͻͻȌǤ ȋ Ȁ Ȍ ǡ Ǥ ȋ Ȍ Ǥ ǣδͳͺεͷǡǦǡ ǡ ǡ Ȁ ǡ ǡ ǡ Ǥʹʹǡ. ͷͲ.
(11) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia Table3.1. . Variable. SAD n = 18. PTSD n = 17. HC n = 22. Gender (n: male/female). 9M/9F. 6M/11F. 9M/13F. 0.8 (X2). ns. Age (yrs). 32.2 (± 3.2). 35.8 (± 3.3). 39.9 (± 2.9). 1.5. Ns. Medication a Antidepressants Sedativesb Otherc Oral contraceptives Social anxiety (SPAI). 7N/11Y 6 4 1 4 156 (± 7.7)d. 4N/13Y 4 2 3 6 131 (± 7.9)d. 17N/5Y 0 0 2 4 89 (± 7.0)d. 12.2 (X2) .002. 21.9. <.001. Depression (BDI). 16.7 (± 2.5)e. 17.9 (± 2.6)f. 3.7 (± 2.3)ef. 10.9. <.001. Early trauma (TEQ) Emotional Physical Sexual. 3.6 (± 0.8) 1.6 (n = 8)h 0.6 (n = 3) 0.2 (n = 1). 7.4 (± 1.0)g 1.5 (n = 6) 1.9 (n = 9)i 2.0 (n = 9)j. 2.7 (± 0.8)g 0.5 (n = 5)h 0.5 (n = 4)i 0.1 ( n = 1)j. 7.9 2.0 4.2 12.9. <.001 .1 .020 <.001. TSST-modificationsk (n) Verbal encouragements Structured speech Speech terminated preterm. 11N/7Y 1 1 5. 11N/6Y 3 0 3. 21N/1Y 1 0 0. 6.8(X2). .033. F value p. Axis-1 comorbidityl (n) 2 2 0 Generalized anxiety d. 1 2 0 Obsessive compulsive d. Panic d. 0 3 0 Depressive d. 0 7 4 0 Dysthymic d. 1 1 Ǥ α Ǣα Ǣ α Ǣ α Ǣ α Ǣ
(12) α
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(15) Ǣα Ǣα Ǥ a ǡ ȋ ȌǤ b ʹͶǤ c
(16) Ǥ d–j ȋp<ǤͲͷȌǤ kDz dz ȋȌ Ǥ l
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(20) ǦȀȌǤ. . Ͷ ȋ ǡnαͳǢǦ ǡ n α ʹǢ ǡnαͳȌǡͳͺǤʹͲǡ͵ ȋ ǡnαͳǢ ǡnαʹȌǡ ͳǤʹʹ Ǥ ǡ . ͷͳ.
(21) Chapter3. ǡ ǡ ȋ ͺǣͲͲ Ȍ ǡ Ǥ ǡ Ǥ ǦǦ Ǥ Ǥ AAtask
(22) Ǧ ȋ Ƭ ǡ ʹͲͲͶȌǡ ǡ ȋǦ ȌȋǦȌ Ǥ ȋ Ƭ ǡ ͳͻǢ ǤǡͳͻͻͺǢƬǡͳͻͻͺǢƬǡͳͻͺͺȌ Ǥȋ ͶͲ ȏͷͲΨ ȐȌǤ ȋͳǦʹǦ ͳǦʹȌ ͳͲ ͳͲ Ǥ ͳͷǦ ͳͶι ͳͲǤιǤ Ǧ ȋ ǡ ʹͲͲͶǡ ǦȌǤ Ǥ Ǧ ȋ Ȍ ǡ Ǥ Ǧ Ǧ Ǧ ǡ ȋͳǦʹȌ ȋͳǦʹȌ Ǧ Ǥ
(23) Ǧ Ǧ ǡ ȋ Ȍ ȋ ȌǤ Ǧ Ǧȋ Ǧǡ ǦȌǤ ǡ ǡ Ǥ Ǧ Ǥ. ͷʹ.
(24) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia. Ǧ ͳʹ ǤͳͲͲǦ Ǧ Ǥ͵ͲͲ ȋ Ȍǡ Ǧ ͳͲͲ ǡ ǦǦ ȋ
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(26) Ȍ ͳͷͲͲ Ǥ ȋ Ǧ Ȍ δ ʹ Ǥ . . TheTrierSocialStressTest ȋͷȌ ȋͷȌǡ ͵ ȋͷ Ȍǡ Ǥ ȋ ǡ Ǣ Ǥǡ ͳͻͻ͵ǡ ȌǤ ͳͷǦ Ͳ Ψ ȋ Ǥǡ ͳͻͻ͵ȌǤ
(27) ǡ ǡ ǡ Ǥ ǣ ͳȌ Ǣ ʹȌ ǡ Ǣ͵Ȍ Ǥ ͵ǤͳǤ Physiologicalandsubjectivemeasures ǡǡ ǡ ǡ Ǧǡ Ǥ ǦͳͲͳ͵ͲǦǦͷǡǦ ͵ͷǡǦʹͷǡǦͳͲǡͲǡΪͳͷǡΪʹͷǡΪͶͲΪͷͲΪͷǡ ǡ ȋ ͵ǤͳȌǤͳǣͲͲ ͶǣͲͲǤ ǡ ȋǡǡ ȌǤǦʹͲι. ͷ͵.
(28) Chapter3. Ǥ ȋ
(29) Ǣ ʹͲͳͲǡ ǡǡȌǡ ȋǤǡʹͲͲ͵ȌǤ ȋ Ȍ ȋͷǦ
(30) Ȍ Ǥ ͳͲǦ DzdzDzdzǤ Questionnaires
(31) ȋ
(32) ǣ ÚƬǡͳͻͻͻǢǤǡͳͻͺͻȌ͵ʹǦ Ǥ ͲͳͻʹǤ
(33) ȋ
(34) Ǧ
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(36) ǣ ǡǡ ǡ ǡ Ƭ ǡ ͳͻͳǢ ǡ ǡ ǡ Ƭ ǡ ͳͻͺͷȌʹͳǦǦ Ǥ Ͳ ͵Ǥ ȋǣ ǡ ǡ Ƭ ǡ ʹͲͲʹȌ ʹǦ Ǧ ǡ Ǥ Ͳʹǡ Ͳǡ Ͳͷǡ ͲǤ Procedure Ǥ ȋȌ ǡ
(37) ǦȀȋʹͷȌȋ͵ǤͳȌǤ ȋȌ ǡ ͳǣͲͲ Ǥ ǡ ǤǦ ȋǦʹͷ Ǣ ͵ǤͳȌǤ ȋ ǡ Ȍ ȋ ȌǤ ǡ ǡ Ǧǡ ȋΪ ʹͷ ȌǤ
(38) ǡ ǦǤ ǡ . ͷͶ.
(39) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia. Ǥ Ǥ Statisticalanalyses δͳͷͲǦ εͳͲͲͲ ǦǤ ǡȋͻΨȌ Ȁ ȋȏǡȐǡ ȏǡ Ȑǡ ȏ ǡȐȌǤ Ǧ ȋǦȌǤ Ǧ ȋ Ǥǡ ͳͻͻ͵Ȍ Ǧ ǡ ǡ Ǧ ȋȌǤ ȋǣ ǡ ǡ ǡƬ ǡʹͲͲ͵ǦʹȌǤ ȋȌ ȋ ǣ ǡǡ Ƭ ǡ ʹͲͲͳȌǤ Ǧ Ǥ ǡ ȋ Ȍ DzǦ dz Ǥ ǤͲͷǤ Ǧ ȋ2ȌǤ Ǧ . Ǧ Ǥ. Results Stressmeasures Ǧ Ǧ ȋ ǡ ǡ Ȍ Ǧ ȋͳͲȌǦ Ǥ. ͷͷ.
(40) Chapter3. Salivary cortisol (nmol/L). 14. 12. 10. SAD PTSD HC. 8. TSST 6. AA task. AA task. 4 -65. -35. -25. -10. 0. +15. +25. +40. +50. +65. Time (in minutes) with reference to onset TSST (Time 0). . Figure 3.1. ȋȌǤ ȋȌ ȋ Ȍ ȋȌǤ ǡ Ǧ Ǥ. . Cortisol Ǧ ȋFȋʹǡͷͶȌαʹǤͷͶǡpαͲǤͲͺǡ2αͲǤͲͻǢ ͵ǤͳȌǤ ǡ Ǧ ǡ ȋFȋʹǡͷͳȌα͵ǤͳͺǡpαͲǤͲͷͲǡ 2αͲǤͳͳȌǤǦ ȋFȋͳǡͷͳȌαͶǤͷͳǡpα ͲǤͲ͵ͻǡ2 αͲǤͲͺȌǤǦ DzǦ dz ȋ Ǧ Ȍ Ǧ DzǦǦ dz ȋFȋͳǡ͵Ȍα ͶǤͳǡ p α ͲǤͲ͵ͺǡ 2 α ͲǤͳͳȌ DzǦǦdz ȋFȋͳǡ͵ʹȌ α ͶǤͷǡ p α ͲǤͲͶͳǡ 2 α ͲǤͳ͵ȌǡDz ǦǦdz ȋFȋͳǡ͵ȌαͲǤͳʹǡnsȌǤ ǡ. u DzǦǦ dzȋFȋʹǡͲȌαͶǤͶͶǡpαͲǤͲʹʹǡ 2 αͲǤͳͳȌDzǦǦdzȋFȋʹǡͷ͵Ȍα͵Ǥ͵ͶǡpαͲǤͲͷͲǡ2 αͲǤͲͻȌ Dz ǦǦ Dz ȋFȋ͵ǡͻͺȌ α ͲǤͺǡ nsȌǤ u Ǧ ȋ ǦͳͲǢ Ǧ ǣ Fȋͳǡ͵Ȍ α ͶǤ͵ǡ p α ͲǤͲͶͶǡ 2 α ͲǤͳͳȌǢ Ǧǣ Fȋͳǡ͵ʹȌ α ͶǤͷǡ p α ͲǤͲ͵ǡ 2 α ͲǤͳ͵Ȍ ͷ.
(41) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia. ȋͳǦͷǣp>ͲǤ͵ͷȌȋ ͵ǤͳȌǤ Ǧ ǡ Ǧ ȋnαȌ ȋnαͳͳǣFȋͳǡʹͳȌαͶǤͳͲǡpαͲǤͲͷǡ2 αͲǤʹͳȌǤ ǡ ǦǦ u ǡ Ǧ ȋ Ȍ Ǧ ȋFȋʹǡͶͷȌαͶǤ͵ͺǡpαͲǤͲʹͻǡ2 αͲǤͳ͵Ȍ Ǧ ȋFȋʹǡͷȌαͳǤʹʹǡnsȌǤǡ. u ǦǦ ǡ Ǧ ȋFȋʹǡ͵ͶȌα͵ǤͶͲǡp=ͲǤͲͷǡ2α ͲǤͳͷȌǦ ȋFȋʹǡͷʹȌαʹǤͶͷǡnsȌǤ Diastolicbloodpressure ȋFȋǡ͵ͷʹȌαͳ͵ǤʹʹǡpδͲǤͲͲͳǡ2αͲǤʹͲȌ Ǧ Ǥ ȋpεͲǤʹȌǤ Subjectiveanxiety ȋFȋͷǡʹȌαͶͶǤͲͷǡpδͲǤͲͲͳǡ2αͲǤͶͷȌ. ȋFȋʹǡͷͶȌ α ͳʹǤͻͳǡ p δ ͲǤͲͲͳǡ 2 α ͲǤ͵ʹȌǤ ǡ Ǧ ȋ p δ ͲǤͲͷȌǤ ȋ p ε ͲǤ͵ȌǤ Ǧ DzǦ dz ȋDzǦǦ dzǣ Fȋͳǡ͵ͺȌ α ʹǤ͵ͻǡ p δ ͲǤͲͲͳǡ 2 α ͲǤͶͳǢ DzǦǦ dzǣ Fȋͳǡ͵Ȍ α ͳͺǤǡ p δ ͲǤͲͲͳǡ 2 α ͲǤ͵ͶȌǡ ȋDzǦǦdzǣFȋͳǡ͵ȌαͲǤͶǡnsȌǤ
(42) ǡǦ ǡ Ǧ Ǥ ǡ ǡ Ǧ ǡ Ǥ
(43) ǡǦ ȋȌ Ǥ ͷ.
(44) Chapter3. *. RT (in ms). 730. SAD. **. 710. 690. 670. 650. RT (in ms). 730. Baseline. PTSD. 710. Stress. Approach Avoid. 690. 670. 650. RT (in ms). 730. Baseline. Stress. Baseline. Stress. HC. 710. 690. 670. 650. . Figure3.2. ȋǢ Ȍ Ǧǡ Ǥ ȋǡ Ȍuȋ ǡȌ Ǧ Ǥ ǡ Ǧ ǡ Ǥ ͳǤȗδǤͲͷǢȗȗδǤͲͳ. EffectsofstressinducedcortisolonthreatavoidanceinSAD ȋǦ ǦȌ ǦǦ ͷͺ.
(45) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia Table3.2. Ǧ . AngryFaceResponses. . . . . ͻͷ ȋʹͶȌ. . ͻ ȋʹͲȌ. ȋʹͳȌ. ʹͲ ȋͳͺȌ. Ͷ ȋʹʹȌ. ͺͲ ȋͳͻȌ. Ǥͷȋ ʹǤͳȌ. . ͻǤ ͻǤͶ ȋʹǤʹȌ ȋͳǤͻȌ. Ǥͷ ȋͳǤͺȌ. Ǥʹȋ ʹǤͷȌ. ǤͶ ͻǤͷ ͷǤ͵ ͶǤʹ ȋͳǤͺȌ ȋʹǤͷȌ ȋͳǤȌ ȋʹǤʹȌ. . ͳ͵ ͻ͵ Ͳͺ ȋʹʹȌ ȋʹͶȌ ȋʹʹȌ Ǥʹ ͵Ǥͻ Ǥ ȋʹǤͶȌ ȋʹǤͳȌ ȋʹǤͶȌ . ͲͲ ȋʹ͵Ȍ. . ͳ ȋͳȌ. ͳ ȋʹͲȌ. HappyFaceResponses . ͺ Ͳͳ ͺ͵ Ͳʹ ͵ʹ ͺ͵ ͺͲ ͻ ͻ ͺͶ ͵ͷ ͺͷ ȋʹͷȌ ȋ͵ͲȌ ȋʹȌ ȋ͵ͳȌ ȋʹ͵Ȍ ȋʹȌ ȋʹȌ ȋʹȌ ȋʹȌ ȋʹȌ ȋʹ͵Ȍ ȋʹͶȌ ͶǤͶ ʹǤ Ǥ ͷǤͺ Ǥ ͶǤͳ Ǥ ͶǤ ͶǤͻ ͷǤͻ ͶǤ͵ ʹǤͺ ȋͳǤȌ ȋͳǤȌ ȋͳǤȌ ȋͳǤȌ ȋͳǤͶȌ ȋͳǤͷȌ ȋͳǤͶȌ ȋͳǤȌ ȋͳǤͶȌ ȋͳǤȌ ȋͳǤ͵Ȍ ȋͳǤȌ ȋȌǤα ǢαΨǢα Ǣα Ǣ͵ǤͳǤ. . ǡ ȋǡ Ȍ ȋ ǡ Ȍ Ǧ ȋȌ Ǥ u ȋFȋͳǡͳȌαͷǤͶͻǡpαͲǤͲ͵ʹǡ 2 α ͲǤʹȌǡ ȋFȋͳǡͳȌ α ͺǤ͵ǡ pα ͲǤͲͲͻǡ2 αͲǤ͵ͶȌȋFȋͳǡͳȌαͲǤͶǡnsȌǤ ȋǦ Ȍ ȋ ͵Ǥʹ ͵ǤʹȌǤ ǡ u u ȋFȋͳǡͳȌ α Ǥͷͷǡ p = ͲǤͲʹͳǡ 2α ͲǤʹͻȌ ǯ Ǧ Ǧ Ǥ Ǧ Ǧ ȋο Ǧ Ȍ ȋrαͲǤͷͶǡpαͲǤͲʹǢ ͵Ǥ͵Ȍǡ Ǥ ȋr α ǦͲǤͲǡ p α ͲǤͻǢ ͵Ǥ͵Ȍ ȋrαͲǤͳ͵ǡpαͲǤ͵ȌǤu ǡ Ǧ ǡ Ǧ ǦǤ u ȋFȋͳǡͳ͵Ȍ α ͶǤͲǡ p = 0ǤͲͷǡ 2 α ͲǤʹȌ u u ȋFȋͳǡͳ͵Ȍ α ͷǤͳǡ p = ͲǤͲͶͳǡ 2 α ͲǤʹͻȌ ȋpεͲǤʹȌǤ
(46) ǡ. ͷͻ.
(47) Chapter3. . AA-effect for angry faces. A. B. SAD patients. 300 250 200 150 100 50 0 -50 -100 -150 -200 -250. (r=.54, p=.02) 0. 500. 1000. 1500. 2000. Salivary cortisol (AUCg). Healthy controls. 300 250 200 150 100 50 0 -50 -100 -150 -200 -250. (r=-.06, p=.79) 0. 500. 1000. 1500. 2000. Salivary cortisol (AUCg). . Figure3.3. ȋ ȏȐȌǦ Ǧ ȋοǦ Ȍ ȋȌ ȋȌ ȋ Ȍ ȋȌǤ Ǧ ǡ Ǧ Ǧ Ǥ ȋȌǤǦ ǡ ǦǢοǦ αȋȏDz Ǧ dz Ȑ Ȃ ȏDz dz ȐȌǤ ο Ǧ Ǧ ǡ Ǥǡ Ǥ. .
(48) Ǧ
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(50) Ǧ ǦǦǤuȋFȋͳǡͳͷȌαͻǤͷͲǡp= ͲǤͲͲͺǡ2αͲǤ͵ͻȌuuȋFȋͳǡͳͷȌαǤͶͷǡp=ͲǤͲͳͷǡ2α ͲǤ͵Ȍ Ǧ ȋFȋͳǡͳͷȌαͲǤͶǡnsȌǤ ǡ Ǧ Ǧ ǡ ȋȌοǦ Ǥ ͺΨ οǦ ȋR2 αͲǤͶǡFȋ͵ǡͳȌα͵ǤͷǡpαͲǤͲͶʹȌ ȋ͵Ǥ͵ȌǤ Ǧ Ǥ
(51) ǡuǦ ȋpεͲǤͶǢ ͵ǤʹȌǤ. Ͳ.
(52) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia Table3.3. Ǧ Ǧ ȋοǦ ȌǤ. Predictor (Constant) ȋȌ ȋȌ ȋȌ. Beta ͲǤͺ ͲǤͳͳ ͲǤͶͲ. T ǦͳǤͶ ʹǤͷ ͲǤͶ ͳǤͶ. P ns ͲǤͲʹ ns ns. ǣR2αͲǤͶȋFȋ͵ǡͳȌα͵ǤͷǡpαͲǤͲͶʹȌ ο Ǧ ǡ Ǧ Ǣ ǡ Ǣ ǡ Ǥ. . ͵Ǥʹ Ǧ Ǧ Ǥ Ǧ ǦǦ Ǧ Ǧ u Ǧ ȋFȋʹǡͷͶȌ α ͵Ǥͳǡp=ͲǤͲ͵ͳǡ2 αͲǤͳʹȌǡ Ǧ ȋ p ε ͲǤʹȌǤ ȋFȋʹǡͷͶȌαͲǤʹ͵ǡnsȌǤ ǡ ȋpεͲǤͳǢ͵ǤʹȌǤ. Discussion Ǧ ȋȌǤ Ǥ ǡ ǡ ǡ Ǧ Ǥ ǡ Ǥ ǡ Ǥ Ǥ ǡ Ǥ Ǧ Ǥ ȋʹͲͲʹȌǡ ȋȌ ȀǤ . ͳ.
(53) Chapter3. ǤȋͳͻͻͻȌǤȋͳͻͻ͵Ȍ ǡ Ǥ ǤȋʹͲͲͳȌ ȋ Ǧ ǦȌǤ Ǧ Ǥ Ǧ Ǧ ǦǤ ǡ ͳͺ Ǥ ǡ ȋǤǤǡ ǡ ǡ ȌǤ Ǥǡ Ǥ Ǥ Ǧ ȋ ǤǡʹͲͲȌǤ ǦȋǡǡǡƬǡͳͻͻͻǢǤǡʹͲͲͷȌǡ ǡǤ ǡ ǦǤǦ Ǥ ǡ ǡ Ǧ ȋǤǡͳͻͻͺǢǡͳͻͻͲȌǤ ǤȋʹͲͲȌ Ǧ ȋȌ Ǥ ǡ ʹ ȋ Ȍ Ǧ ǡ Ǥ Ǧ. ʹ.
(54) Cortisolreactivitypredictsavoidancebehaviorinsocialphobia. ȋǤǡ ʹͲͲʹǢ Ǥǡ ͳͻͻͻǢ ǡ ͳͻͻͲȌ Ǥǡ Ǧ Ǧ Ǥ Ǧ Ǧ Ǧ ȋ Ȍ Ǧǡ
(55) ǦǦȋǤǡʹͲͲͻȌǤ Ǧ ȋ Ǧ Ȍ ȋǤǤǡǡǡ ǡ Ƭ ǡ ʹͲͲͲǢ ǡ ǡ ǡ Ƭ ǡ ʹͲͲͲȌǤ Ǧ Ǧ Ǥ Ǧ Ǥ ǡ Ǧ Ǥ Ǥ ǡ Ǧ ȋ ǦȌ ȋǦȌȋ ǤǡʹͲͲ͵Ǣ Ƭ ǡ ͳͻͻͶȌǤ Ǧ ǦǤ Ǧ ȋ ǡ ǡ ǡ Ƭ ǡ ʹͲͲͶȌǤ ǡ Ǧ ǡ Ǥ ǡ ǡ Ǧ Ǥ
(56) ǡ Ǧ Ǥ ǡ ǡ Ǥ. ͵.
(57) Chapter3. ǡ Ǧ Ǥ ǡ ǦǤ Ǧ Ǧ Ǥ ȋ Ǧ ǡ Ȍ Ǥ ȋͳͻͷͺȌ Ǥ ǡ Ǧ Ǥ. Ͷ.
(58)
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