A Tale of 3 Cities, the Maastricht Masters &

the Tryptophan Depletion story

Professor Sean HoodConsultant Psychiatrist

University of Western AustraliaPerth, Australia

Servier + Pfizer Support

City # 1: Bristol

Tryptophan Depletion in Social Anxiety Disorder.

Dr Sean Hood

Presented at The European Certificate in Anxiety and Mood Disorders, Santa Margherita Ligure, 2000

Tryptophan Depletion: Serotonin & Anxiety

Study Protocol Overview

Recruitment

Patient fails to respond to standard open treatment (by CGI-I score):

Routine outpatient care

Exclusion Criteria met: Routine outpatient care

Post-Study Follow-upScreening Day

Exclusion Criteria met: Routine outpatient care

Day 1 Day 2Standard open treatment3/12+ SSRI

Tryptophan Depletion: Serotonin & Anxiety

SAnD TD: Protocol

Amino acid drink

0 +1 +2 +3 +4 +5 +6 +7

TRP Levels

TRPLevels

TRPLevels

Time (hrs)

TRPLevels

#3:#3:NeutralNeutralScriptScript

#2:#2:VerbalVerbalTaskTask

#1: Autobiographical

Script

(fasting)

Qu. +2 hr Qu. +4 hr

• Subjects: n=14 SSRI-remitted SAnD (CGI 1 or 2)

• Challenge: Autobiog. Script,Verbal Task, N.

task• Measures:

SSAI,VAS,LSAS,SPINCVS

• Subjects: n=14 SSRI-remitted SAnD (CGI 1 or 2)

• Challenge: Autobiog. Script,Verbal Task, N.

task• Measures:

SSAI,VAS,LSAS,SPINCVS

• Results: ATD

Total [TRP] over time (+/- SD)

0 1 2 3 4 5 6 7 80

10

20

30

40TRP DepletedNormal TRP

** (Wilcoxon z=-3.297, p<0.001)

** (Wilcoxon z=-3.181,p<0.001)

Time (hours)

To

tal

[TR

P]

(m

ols

/L)

Baseline 4 Hours A Script Verbal N Script 20

30

40

50

Depletion

Control

Figure 2: Spielberger State Anxiety Inventory (STAI form Y-1) score across thesessions. A Script: autobiographical script; Verbal: verbal stressful task; N Script:

neutral script. a: Wilcoxon z = -1.995, p = 0.046; b: Wilcoxon: z = -2.279; p =

0.023; c: Wilcoxon z = -2.199; p = 0.028.

ac

b

Session

SS

AI

sco

re

0 Baseline 4 Hours A Script Verbal N Script 0

5

10

15

20

Depletion

Control

Figure 1: Visual Analogue Scales composite score across the sessions.A Script: autobiographical script; Verbal: verbal stressful task; N Script: neutral

script; a: Wilcoxon z = -2.043; p = 0.041.

a

Session

VA

S s

core

City # 2: Maastricht

2004 Summer Conference of the British Association for Psychopharmacology. Harrogate, UK.

Acute Tryptophan Depletion in 5 clinical anxiety disorders:

PD, SAnD, PTSD, GAD & OCD

NeurotalkJune 27th, 2010

Singapore

Professor Sean HoodConsultant Psychiatrist

University of Western AustraliaPerth, Australia

5 Clinical Anxiety Disorders

Acute Tryptophan Depletion:Serotonin & Anxiety

• Acutely Depleting Serotonin Sx– (SSRI-remitted Depression)– SSRI-remitted SAnD (Social Anxiety)– SSRI-remitted PD (Panic)– CBT-remitted PD (Panic)– SSRI-remitted PTSD

• Acutely Depleting Serotonin NO Sx– SSRI-remitted GAD (Generalised Anxiety)– SSRI-remitted OCD (Obsessive Compulsive)

ATD in Anxiety Summary

City # 3: Perth

Serotonin – HPA

Serotonin – HPA

5HT & Hypertension & Stress(N) Volunteer Studies completed

Study ATD 35% CO2 SSRICompleted Pre-1: ATD Vols

(Shufflebotham et al. 2006)

Pre-2: CO2 Vols (Shufflebotham et al. 2009)

Pre-3: ATD CO2 Vols (Hood et al. 2006)

Pre-4: ATD CO2 SSRI Vols(Hince et al. 2010)

(3 weeks)

5HT & Hypertension & Stress(N) Volunteer Studies over Past 5 Years

Significant Outcome Measures for Normal Volunteers

Study Psychological Cardiovascular EndocrinePre-1: ATD Vols (Shufflebotham, Hood, Hendry, Hince, Morris, Nutt, Probert, & Potokar 2006)

Nil: ATD Nil: ATD -

Pre-2: CO2 Vols (Shufflebotham, Wetherell, Hince, Hood, Lightman, Nutt, Probert, & Potokar 2009)

CO2 anxiety CO2 BP CO2 Cortisol

Pre-3: ATD CO2 Vols (Hood, Hince, Robinson, Cirillo, Christmas, & Kaye 2006)

Nil: ATD CO2 anxietyNil: ATD x CO2

ATD BP (trend)CO2 BPNil: ATD x CO2

ATD CortisolCO2 CortisolNil: ATD x CO2

Pre-4: ATD CO2 SSRI Vols(Hince, Menon, Shadianloo, & Hood 2010)

Nil: ATDCO2 anxietyNil: 3 wk SSRINil: ATD x CO2Nil: ATD x 3 wk SSRICO2 x 3 wk SSRI anxiety

Nil: ATDCO2 BPNil: 3 wk SSRI Nil: ATD x CO2Nil: ATD x 3 wk SSRINil: CO2 x 3 wk SSRI

-

Serotonin – Cardiovascular

5HT & Hypertension & StressDavies, Hood et al. J Clin Psychopharm.

P & H: Autonomic Dysfunction

P & H: Autonomic Dysfunction

Networking

P & H: Autonomic Dysfunction

From Rags to Riches in 10 years:

How the Maastricht Masters made me fantastically successful.

Professor Sean HoodConsultant PsychiatristUniversity of Western AustraliaPerth, Australia