Vous êtes sur la page 1sur 14

7/6/11

Melancholia (Hippocrates)

Association melancholia-euphoria in the


same individual (Araeteus)

Carlo Faravelli

E. Krepelin: manic depressive insanity as separated from


dementia praecox
Psychoses and neurosis

E. Kraepelin:
Depression = manic depressive
illness, regardless of whether or
not mania had occurred

Coexistence of M and D in the same


persons
Same depressive symptoms
Same course (recurrent)
Same outcome
Same premorbid personality
Same family concentration
The places

The sample

The remedies

1
7/6/11

Since 1960
ECT, antidepressants
Reduction of admissions to Mental Hospitals, tremendous increase of
outpatient psychiatric practice

Efficacious
Side effects not particularly relevant Dramatic change in psychiatric samples:
Relative decrease of psychoses and other severe forms
Enormous increase of neurotic disorders

Since 1960, in psychiatric samples:

Milder depressive syndromes become more and more frequent


The former ratio of depressives with mania to depressives without
mania decreases

ADs Psychiatric samples are now characterised by a majority of mild


depressive states, without severe/endogenous/psychotic features

Maudsley vs Newcastle
Leonhard, Angst, Perris (independently)

Debate on the unitary –


Increase in
tolerability
Distinction binary nosological status
UNIPOLAR-BIPOLAR of depression

MODELS OF DEPRESSION CATEGORY DIMENSION

Unitary model Reactive HEALTHY ILL


Endogenous HEALTHY ILL
(Lewis, Kendell)

Either - Or Some
Dualistic Model
Endogenous Reactive
(Roth and several
others)

2
7/6/11

1965 UK-US study (Wing, Cooper & Sartorius) 


variability of diagnostic approach

Need for reliability/


reproducibitlity

Major Depression = presence of a certain


number of symptoms DSM IV Classification of Mood Disorders

1972 St. Louis

RDC (1975-8) 296.2 Major Depressive Disorder, Single Episode


296.3 Major Depressive Disorder, Recurrent
DSM III (1980)
300.4 Dysthymic Disorder
DSM III-R (1987) 311 Depressive Disorder N.O.S.
296 Bipolar I Disorder (Single Manic, Most recent ep. manic, mixed, ......)
ICD - 10 (1993) 296.89 Bipolar II Disorder
296.80 Bipolar Disorders N.O.S.
DSM IV (1994)
301.13 Cyclothymic Disorder
293.83 Mood Disorder Due to a General Medical Condition
xxx Substance Induced Mood Disorder
2011 DSM V

DSM III  DSM IV


DSM IV Classification of Depression Implicit concepts

SPECIFIERS
• Quantitative hypotesis (= extreme variation of normality)
# sympt. PSYCHOTIC MELANCHOLIC ATYPICAL CATATONIC
• Bipolar # Unipolar
-  1+4 Major Depressive episode X X X X
-  2-3 Dysthymic Disorder X • Reliability > Validity
-  <2 Depressive Disorder N.O.S. • Definition based on manifest symptoms

  Premenstrual Dysphoric Disorder


Ž  Minor Depressive Disorder Depressio sine depressione
 Ž Recurrent Brief Depressive Disorder Masked depression
 Ž Postpsychotic depression of schizophrenia
 Ž Major Depressive Disorder Superimposed on Delusional D. Psychotic Depressive equivalent
 Ž D. NOS or the active phase of Schizophrenia Depressive pseudodementia
 Ž Other depressive situations
…..
no longer diagnosable

3
7/6/11

DSM iV quantitative hypothesis

DSM IV Major Depressive Episode


Depressed mood
Depressed mood Depressed mood
Diminished interest or pleasure Depression = syndrome
Diminished interest or pleasure Diminished interest or pleasure
Weight loss
Weight loss/gain
Weight gain Subcategories prevalently differ as regards severity
Insomnia/hypersomnia (quantitative distinction)
Psychomotor retardation hypersomnia
Psychomotor agitation/retardation
Worthlessness, inappropriate guilt Fatigue Severity = pervasiveness (extension)
Fatigue, loss of energy
Diminished concentration, indecisiveness
Corollary:
Worthlessness, inappropriate guilt
Suicidal ideation
Diminished concentration, indecisiveness any subset symptoms (among those listed) is
Suicidal ideation necessary and sufficient to make the diagnosis
all the symptoms have the same value

CHALLENGING DSM IV Comprehensive Psychiatry, 5:307-315, 1996

Number of symptoms, quantification, and qualification of depression


The basic question is whether all the depressive Faravelli C., Servi P., Arends J.A., Strik W.K.
symptoms are equivalent or whether some specific
symptoms should be given higher diagnostic priority.
SUMMARY
Hypothesis Current classification systems (ICD-10, DSM IV) require a quantitative criterion for differentiating
depressive states, suggesting a correlation between the number of symptoms, i.e the pervasiveness, and
the subtype of the illness. All the symptoms (within those comprised in the diagnostic lists) are assumed
•  Some special symptoms have greater value to have comparable value. In order to investigate the relevance of the number and the type of symptoms
reported by 196 patients suffering from depression, we compared the symptoms with independent
than others indicators of severity such as Clinical Global Impression (CGI) and Social Functioning (GAF). A second
comparison using the same indicators was made between qualitatively distinct categories of DSM IV and
•  Some symptoms reflect qualitative rather than ICD-10 (i.e. melancholic patients vs non melancholic, patients with somatic symdrome vs non somatic
and psychotic vs non psychotic). Whereas there was a certain evidence that increasing numbers of
quantitative differences symptoms actually reflects higher levels of severity, the categorization that were mainly based on
qualitative criteria (e.g. melancholics, somatic syndrome, etc) usually attained better discrimination
compared to those based on the number of symptoms. Moreover, some specific symptoms (usually those
•  The presence of some symptoms, per se, is indicated as endogeous) are more likely to be associated with greater severity and pervasiveness. Finally
it resulted clear that different symptoms bore different weights in establishing the gradient of severity,
indicative of greater severity thus contradicting DSM IV implicit assumption that depressive symptoms are equivalent.

The number of symptoms Some symptoms are associated with:


as the main factor to
classify depressions is Greater severity
not supported by the Greater suicidal risk
Greater risk to switch into mania
evidence
Greater risk of recurrence
Higher family concentration
Better response to drug treatment

4
7/6/11

Subthreshold depression

Delusion
Guilt
Psychomotor retardation
Psyhic agitation
Anhedonia
Suicidal ideation

Sesto Fiorentino Study

Lifetime Prevalence %
depressive symptoms by duration

DEPRESSION Presence of certain symptoms,


Sub-threshold
in a given number,
for a given period of time

1.  symptom(s) below the level of definite (very mild or


fluctuating) % WITH RECURRENT COURSE:
Sub-MD (>4 symptoms for less than 2 weeks) 52
2.  fewer symptoms than required Sub-Dysthymia (2-4 symptoms for less than 2 yr) 40

3.  duration shorter than required Faravelli et al 2004

Number of symptoms Number of symptoms

Angst 1990

Faravelli et al 2004

5
7/6/11

Unipolar vs Bipolar

Subthreshold depression may be as


severe and disabling as fully blown
depression

Bipolar affective disorder


Bipolar illness

Essential features:
presence of manic and 50%
Half thewith
cases with bipolar
depressive episodes during
the life of the same
Diagnosis of Bipolar MANIAreceive an initial
disorder
diagnosis of non bipolar
only possible after a
individual; recurrent course
disorder
Diagnostic requirement:
having or having had one (hypo)manic episode
single (hypo)manic episode 50% without
MANIA

1500 subjects treated with AD for the first time in their life, for whatever
5-30% of unipolars become reason: 50 manic switches after 3 year follow-up (Gorini et al 2006)
bipolars during follow-up (9
studies)

Is it possible to predict bipolarity ? Racing thougths


Risk of becoming
bipolar Guilt/Inadequacy
Predictors of mania in unipolars:
early onset, family history for Bip, Depressive mood
shorter cycles, males, hyperthymic
personality, personality disorder, Anedonia
depressive symptoms (several
EARLIER FAMILY Suicidal ideation
reports)
ONSET HISTORY FOR
BIPOLAR

6
7/6/11

M Does
MDI

D
drug
induced
mania
M exist ?
DMI
D

antidepressants

Comparison between
35 cases in whom the first manic episode was spontaneous
vs.
34 cases in whom the first manic episode occurred during treatment with
antidepressants
The DIAGNOSIS OF MANIA
Follow-up 3-15 years

1.  Family history


2.  Total number of episodes
NO DIFFERENCE
3.  D/M ratio
4.  Suicidal behaviours

26% of those with “induced mania” had spontaneous episodes


of mania during follow-up

DSM-IV: MANIC EPISODE Delirious Mania


Mania

Abnormally elevated expansive or irritable mood (at least one week)


“Manic excitement in its most severe form leads
3 (4 if irritable mood) of the following:
Self esteem or grandiosity
to confusion, in which the typical symptoms of
Decreased need for sleep
More talkative than usual mania are obscured. Consciousness, which is
Flight of ideas or pressure to keelp talking
Distractibility clear in the less severe states, becomes clouded,
Increase in activities
Excessive involvement in activities with potentially painful consequences illusions and hallucinations may be observed,
Social-occupational impairment and the condition may resemble a delirium.
[Exclusion criteria: mixed state, due to substances]
These states are seriously debilitating and may
endanger life.”

Mayer-Gross, Slater & Roth, 1960

7
7/6/11

Stages of mania
Acute Mania: behaviour (adapted from Carlson & Goodwin,1973)
Mania

lability of affect, euphoria, irritability


“In the more acute manic reactions the patient, driven by ONLY STAGE I MEETS THE
STAGE I expansivity, grandiosity, overconfidence
a greater pressure of activity, terror and excitement, CRITERIA FOR MANIA
increased psychomotor activity, spending, smoking, ..
becomes violent, attacks his neighbours or begins to
shout all kinds of accusations against his alleged
persecutors.....Distortions, misinterpretations and ideas increased dysphoria and depression, hostility and anger
of reference are now elaborated into delusions of
flight of ideas, delusions
persecution accompanied by violence and panic. The STAGE II
patient runs down the street nude, sets fire to the house, psychomotor acceleration, assaultive behaviour
starts an argument with the police, .......If crossed or
interfered with in any way he becomes abusive,
clearly dysphoric, panic stricken, hopeless
destructive..”
STAGE III loosening of associations, hallucinations in 1/3 of patients
Campbell, 1953
bizzarre psychomotor activity

Conclusions

Is it possible to catch an extremely dynamic entity /concept using fixed


criteria ?
(= representing a movie with a single photograph)

Operational vs prototypal criteria for mood disorders ?

% frequence of
depressive symptoms by
diagnosis in a clinical
sample

100

90

80

The relationship of symptoms to 70

diagnoses: any specificity ? 60

50

40

30
Are affective symptoms selectively associated 20 Concentration
Agitation
with affective diagnoses ? Guilt
10 Retardation
Self esteem
0
Thoughts of death
Loss of pleasure
E
D

ia
M

bia
an

Depressed mood
AD
M

ho

D
G

C
lP

is
O

n
cia

ho

pa

is
D
So

yc

g
Ps

tin
Ea

8
7/6/11

% Frequency of affective symptoms


by diagnosis in a community sample

120

100

80
EDM (242) Affective (depression and anxiety) symptoms bear weak (if any) association with
Dep nas (207) anxiety and mood operational diagnoses. They rather range across a variety of
GAD (179) clinical conditions other than depressive disorders
60
PDA (65)
Ansia nas (216)
OCD (63)
40 D_Abuso sost (18)
FobSoc (92)
Psicosi (13)

20 Anoressia (7

0
ss

ia

te

az

ic

nia

cis

tia

lia
z

zz

tt
at
ra
im

olp

or

fe
Ps
on

or
re

u
te
it

a
M
de
te
nt

af
m
Ag

Ab
st

Ap
M

an
ep

ed

all

io
As
ce

U
In
to

ttim
gg
R

s
D

An

Au

ttiv
on

Pe

Pe

pia
C

ea

Ap
R

Attention on neurotrasmitters, as opposed to psychological factors

Gender (F : M = 2 : 1)
Family concentration
Adverse life events

LIFE EVENTS and PSYCHOPATHOLOGY


British Journal of Psychiatry, 147: 288-295, 1986

Early life events and affective disorders revisited.


Faravelli, C., Ambonetti, A., Pallanti, S., Sacchetti, E., Conte, G., Vita, A
Events during childhood (predisposing factor)

Abuse
Neglect
Loss

Solid evidence for mood disorder, substance abuse, anxiety disorders,


eating disorders, substance dependence/abuse, borderline personality
disorders in adults

Early traumata % (death of parent, prolonged separation from parents, death of


cohabiting relative) during the first 10 years of life

9
7/6/11

Life Events prior to the onset of Psychopathology (precipitating factor)


LIFE EVENTS, DEPRESSION & GENETIC RISK

Major Depression: •  Several studies show that the onset of the first depressive
excess events episode is often preceded by a stressful event
20/26 studies
• Life Events are also related with the risk of recurrences

•  The impact of Life Events is reduced when the disorder is


severe and recurrent

•  The response to stressful events is mediated by a specific


genetic vulnerability

Paykel et al 2003

Is the excess of stressful life events


specific to mood disorders ?

Stressful Life Events Increase Depression


Risk in S/S Homozygotes

Science, 2003

Anxiety disorders
12/14

10
7/6/11

Sesto Fiorentino Study

Severe life events in the year prior to the


onset of psychiatric disorders (OR) in the
community Life events are precipitating factors for
(almost) all psychiatric disorders

Are there symptoms that are specifically


triggered by stressful life events ?

Sesto Fiorentino Study Symptoms triggered by life events

Depression .65966
Anhedonia .59182
Concentration .51106
Anxiety, psychic .50568
Insomnia, initial .49690
Insomnia, central .42546
Insomnia, terminal .37722
Fatigue .37441
Psychic Retardation
Loss of drive
.35515
.33799
Almost of the disorders, but relatively few
Weight loss
Suicidal ideation
.32220
.30679 symptoms are associated with stressful
Indecisiveness
Tiredness
.28861
.28856 events
Sexual desire .27728
Abulia .25807
Guilt .21478 By which mechanisms ?
Discriminant Analysis: Hyporexia .21376
Blunted affect .20042
Nightmares .18546
Symptoms vs. Presence/ Worse in the morning .17542
absence of severe stressful Agitation .17484
Panic .16933
events Self-esteem .16661
Night terror .16365
(N = 1043) Somatofom
Obsession
.15825
.15118
[other 80 symptoms with loading < .13]

Nature Neuroscience 7, 841 - 846 (2004) Stress


Early life experience alters response of adult
neurogenesis to stress
Christian Mirescu, Jennifer D Peters & Elizabeth Gould
Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA
cortisol
Nature Neuroscience 7, 899 - 900 (2004)
From neurotoxin to neurotrophin
Christian Mirescu & Elizabeth Gould glucocorticoid receptor
Department of Psychology, Princeton University, Princeton, New Jersey, USA. hyperactivation
HPA axis and
Neonatal lesions of the amigdala alter
psychopathology mother-infant interactions (Bauman et al, CREB inhibition
Neurosci 2004) (cAMP response
element binding,
trascription factors)

expression of BDNF
mRNA in hippocampus
and gyrus dentatus

BDNF

atrophy

11
7/6/11

Psychoneuroendocrinology. 2011 Apr;36(3):415-25.

The glucocorticoid receptor: pivot of depression and of antidepressant


treatment?
Anacker C, Zunszain PA, Carvalho LA, Pariante CM.
King's College London, Institute of Psychiatry, Centre for the Cellular Basis of Behaviour (CCBB), Department of Psychological
Medicine, Section of Perinatal Psychiatry & Stress, Psychiatry and Immunology (SPI-lab), 125 Coldharbour Lane, London SE5
9NU, UK.

Abstract
Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and increased levels of glucocorticoid hormones in
patients with depression have mostly been ascribed to impaired feedback regulation of the HPA axis, possibly
caused by altered function of the receptor for glucocorticoid hormones, the glucocorticoid receptor (GR).
Antidepressants, in turn, ameliorate many of the neurobiological disturbances in depression, including HPA axis
hyperactivity, and thereby alleviate depressive symptoms. There is strong evidence for the notion that
antidepressants exert these effects by modulating the GR. Such modulations, however, can be manifold and range
from regulation of receptor expression to post-translational modifications, which may result in differences in GR
nuclear translocation and GR-dependent gene transcription. The idea that the therapeutic action of antidepressants
is mediated, at least in part, by restoring GR function, is consistent with studies showing that decreased GR function
contributes to HPA axis hyperactivity and to the development of depressive symptoms. Conversely, excessive
glucocorticoid signalling, which requires an active GR, is associated with functional impairments in the depressed
brain, especially in the hippocampus, where it results in reduced neurogenesis and impaired neuroplasticity. In this
review, we will focus on the GR as a key player in the precipitation, development and resolution of depression. We
will discuss potential explanations for the apparent controversy between glucocorticoid resistance and the
detrimental effects of excessive glucocorticoid signalling. We will review some of the evidence for modulation of the
GR by antidepressants and we will provide further insight into how antidepressants may regulate the GR to
overcome depressive symptoms.

Experimental group Sample Kind of study Control group Cortisol Acth


HPA axis and Linkowski et al 1985 18 MD men plasma Basal level 7 healthy controls ↑ =

Major Depression Mortola et al 1987 6 MD women plasma Basal level 8 healthy women
↑ 24 hours transverse
mean cortisol
↑ pulse frequency
44 MD, 35 partial or
↑ in depression in the
Michael et al 2000 complete remitted saliva Basal level 41 healthy volunteers −
evening
depression
Weber et al 2000 25 severe MD plasma Basal level 30 healthy volunteers ↑ −
29 mixed anxiety
Kara et al 2000 31 MD plasma DST = −
depressive
6 inpatients recurrent Infusion of a low
Kellner et al 1995 plasma 6 healthy volunteers = =
MD dose of cortisol
No increase in
Response to daily cortisol following
Peeters et al 2004 47 saliva 39 healthy controls −
events negative events (↑ in

Major Depression:
Kathol et al 1989 31 MD urine Urinary free cortisol
65 panic disorder;
healthy)

↑ Is an abnormal HPA function specific to


36 healthy controls

abnormal HPA Depressive disorders ?


↑ in patients with
24-hours cortisol
Yehuda et al 1993 urine MD and bipolar
excretion
Mania
10 atypical = plasma; low CSF
Geracioti et al 1997 Plasma, CSF Basal level 15 healthy controls Low plasma
depression CRH
Banki et al 1992
15/23 CSF CRH basal level Crh =
Normal plasma
Wong et al 2000 MD CSF CRH basal level ↑
ACTH and CSF CRH
Kunugi et al 2004 20 inpatients MD plasma DEX/CRH 30 healthy controls ↑ −

Carrol 1982 plasma DST ↑

Deushle et al 1997 15 severe MD plasma Basal level 22 healthy controls ↑ ↑

Weber et al 2000 25 severe MD plasma Basal level 30 healthy controls ↑ -


Bhagwagar et al 31 depressed
saliva Basal level 31 healthy controls ↑ -
2003 inpatients
Board et al 1956 plasma Basal level ↑

11 psychotic MD, 38 ↓ in MPMD, =in NPMD,


Posener et al 2000 plasma 24-hours basal level 33 healthy controls
NPMD = in PMD ↑ in PMD
Administration of
Posener et al 2001 29 MD plasma 25 healthy controls - =
cortisol or placebo
148 inpatients (of 12 outpatients, 17 ↑ inpatients compare
Copolov et al 1989 saliva DST
whome 71 MD) healthy volunteers as outpatients
six-fold higher risk
74 remitted MD
Holsboer et al 1986 plasma CRH/DST no for relapse in pt with
patients
higher cortisol

12
7/6/11

HPA axis and


Sample Kind of study Cortisol levels ACTH levels Control Experimental group
Anxiety disorders group
HPA axis and Nesse et al. 1984 Plasma Basal levels ↑ - 6 inpatient 14

Bipolar Disorder Experimental


Roy-Byrne et al. 1986
Goldstein et al. 1987
Plasma
Plasma
Basal levels
Basal levels


-
-
30
61 healthy and 38 MD
8
24 outpatients
Sample Kind of study Control group Cortisol Acth
group outpatients
Abelson et al. 1996 Plasma Basal levels ↑ - 12 20
50 manic Wedekind et al. 2000 Plasma Basal levels ↑ - 23 47
Graham et al 1982 plasma DST ↑( no suppression 46%) -
patients Lopez et al. 1990 Urine Basal levels ↑ - 37 66
↑(no suppression
10 bipolar (7 Bandelow et al. 1997 Urine Basal levels ↑ - 13 16 male
Evans et al 1983 plasma DST 100%of mixed, 0% of -
mixed, 3 manic) Wedekind et al. 2000 Saliva Basal levels ↑ No 25 during panic-attack
manic)
Bandelow et al. 2000 Saliva Basal levels ↑ 23 23
40 manic
Godwin 1984 plasma DST ↑(no suppression 60%) - Brambilla et al. 1992 Plasma Basal levels - ↑ 14 17
patients
Bipolar disorder Roy-Byrne et al. 1986 Plasma CRH-stimulation ↓ ↑ 30 8
Plasma Brambilla et al. 1992 Plasma CRH- stimulation ↓ ↑ 14 17
Swann et al 1992 CSF DST
abnormal HPA urine
Holsboer et al.
Liebowitz et al. 1985
1987 Plasma
Plasma
CRH- stimulation
BasalAnxiety
levels disorders
=
= ↑
20 43
Schmider et al 1995 11 acute manic plasma DST/CRH 11 healthy volunteers ↑ ↑ Cameron et al. 1987 Plasma Basal levels = 4 8

487 depressed
↑( no suppression Villacres et al. 1987 Plasma Abnormal HPA
Basal levels = 10 10
27%of all patients with Stein et al. 1988 Plasma Basal levels = 10 MD (4 unipolar and 6 10
Rush et al 1996 (422 unipolar, plasma DST -
11/12
65 bipolar)
major depression, 43% of
all bipolar depressed)
Woods et al. 1988 Plasma Basal levels 21/33 =
bipolar) and 10 healthy
19 14 panic
Gurguis et al. 1991 Plasma Basal levels = 12 32 panic and agoraphobic
42 bipolar in
Vieta et al 1997 plasma CRH 21 healthy volunteers ↑ ↑ Brambilla et al. 1992 Plasma Basal levels = 14 17 panic
remission
44 bipolar (37 ↑(no suppression 43% of Brambilla et al. 1995 Plasma Basal levels = 12 12 panic and agoraphobic
Cassidy et al 1998 plasma DST not -
manic, 7 mixed) manic, 86% of mixed) Uhde et al. 1988 Urine Basal levels = 12 12 panic
↑ compared with Rapaport et al. 1989 Plasma CRH-stimulation = = 8 8 panic
40 depressed
Janusz et al 1999 plasma DST/CRH 20 healthy volunteers unipolar ones and with - Jolkkonen et al. 1993 CSF CRH-basal levels = 8 33 panic with or without agoraphobia
(16 B, 24 U)
control subjects Avery et al. 1985 Plasma DST (no suppression) NO 22 panic and 13 agoraphobic with panic attack
18 bipolar (5 D,
Judd et al. 1987 Plasma DST 29% (no suppression) 21 35 panic
Cervantes et al 2001 5 M, plasma Basal level 5 healthy volunteers ↑ -
8 euthymic) Coryell & Noyes 1988 Plasma DST (no suppression) 52 patients with PD after 52 panic or agoraphobic with panic attack
placebo
Deshauer et al 2003 saliva ↑ - Westberg et al.1991 Plasma DST 28% of panic with 49 31 panic and 32 panic with agoraphobia
agoraphobia (no suppression)
Schreiber et al. 1996 Plasma DST/CRH ↑ (no suppression) 10 13 panic
Plasma DST
Watson et al 2004 53 bipolar 28 healthy volunteers ↑ - Curtis et al. 1982 Plasma DST ↓ NO 10 agoraphobic with panic attack, 6 panic and 4
saliva DST/CRH
either agoraphobic or panic
Lieberman et al 1983 Plasma DST ↓ 22 patients with MD 10 panic
Sheehan et al 1983 Plasma DST ↓ NO 51 panic
Cameron & Nesse 1988 Plasma DST ↓ NO NO

Experimental
Sample Kind of study Control group Cortisol Acth
group
Ryan et al 2004 12 Plasma Basal levels Healthy controls ↑ ↑

HPA axis and Muck-Seler et al 2004 20 Plasma Basal levels Healthy controls ↑ -

HPA axis and Control group Experimental Sample Kind of studty Results Schizophrenia Kaneda et al 2002 53 Plasma Basal levels Healthy controls = ↑

OCD group Rao et al 1995 89 Basal levels Healthy controls = -

Gil-Ad et al 1986 10 Plasma Basal levels Healthy controls ↑ -


Gehris et al. 25 healthy 17 ocd urinary Both neutral and no suppression
1990 aversive stimuli Basal levels = =
exposition Roy et al 1997 9 Plasma -
Crh challenge = =

Kasvikis et al. - 19 ocd urinary Basal cortisol no suppression Basal levels Response to a physical
1988 Jansen et al 2000 18 Saliva and a psychosocial 21 hc = -
stressor

Lucey et al. 1992 5 healthy 10 ocd plasma DST suppression ↑ basal level
Jakovljevic et al 1998 59 Plasma DST - -
51% nonsupp.
Plasma DST - 1/64 nonsupp -
Coryel et al. 1989 82 panico OCD:
20 ocd plasma DST suppression Ismail et al 1998 64
Schizophrenia:
Plasma DST - 56-53% nonsupp -
Pivac et al 1997 80

Catapano et al. 20 healthy abnormal HPA


18 ocd plasma DST no suppression Garyfallos et al 1993 30 abnornal HPA
Plasma DST - 4/30 (13%) nonsupp -

1990 (5 patients= Saliva Basal level - ↑ in 20/33 -

8/10
27.7%) Kaneko et al 1992 33 16/21 DST 13/33 nonsupp

Cottraux et al. - 20 ocd plasma DST no suppression


Tandon et al 1991 44 Plasma DST - 17/44 (40%) nonsupp -
1984 (6 patients=30%)
Plasma DST - 2/22 nonsupp -
Kiriike et al 1988 22
Vallejo et al. 24 (nondepressed 29 ocd + mdd plasma DST no suppression
Plasma DST - 18% nonsupp -
1988 ocd-patients) (5 patients) Sharma et al 1988
Plasma DST - 71% nonsupp (acute) -
Jenike et al. 1987 24 (nondepressed 29 ocd + mdd plasma DST no suppression Wik et al 1986 21 20% nonsupp (treated)
ocd-patients) (5 patients)
40 MDD (52,5%
Monteiro et al. - 61 ocd + mdd plasma DST no suppression nonsupp,
Asnis et al. 1986 17 Plasma DST 30 healthy 23,5% nonsupp -
1986 controls (6,7%
nonsupp)
Insel et al. 1982 - 9 pure ocd and 7 plasma DST no suppression Plasma DST - 7/23 (31%) nonsupp -
Munro et al 1984 23
ocd + mdd (6
patients=37.5%) Plasma DST - 7/20 nonsupp -
Sawyer et al 1984 20

DST 24 healthy 3/24 (13%) nonsupp


Lammers et al 1995 24 Plasma -
DST/CRH controls 9/24 (38%) nonsupp

Risch et al 45 CSF CRF =

Life events Solid evidence of a role in the salivary cortisol after dexamethazone
Suppression Ratio

pathogenesis of psychiatric disorders 1,2

HPA dysfunction Non specific to any diagnostic group 1

0,8

0,6

0,4

0,2

DEX
0 Psych (n= 89) Controls (n= 43)

Mean + 2sd of controls

13
7/6/11

DST NonSuppression by Diagnosis

DEPRESSIVE SYMPTOMS

Symptoms associated with DST nonsuppression (OR)


Bipolarity
Greater severity
One set of symptoms Familiy history
related to:
Worse social functioning
Better response to biological treatments
Delusion
Inadequacy/guilt
Psychic retardation/
agitation
Worse in the morning
Suicidal thoughts

A different set of Childhood trauma


symptoms related to: Recent stressful events
HPA axis dysfunction Depressed mood
Anhedonia
Lack of Concentration
Psychic Anxiety,
Insomnia, initial and middle
Fatigue

STRESS SYMPTOMS AS A CROSS-SECTIONAL


TRANSNOSOGRAPHICAL FEATURE
DSM IV, classification, disorders, illnesses
Delusions of
reference,
hallucinations,
Guilt, retardation, bizarre
worse in the Binges, body behaviour ….
morning, suicidal image , impulse
Obsessions, ideation, dyscontrol,...
compulsions, indecision,
delusion,..

Panic,
agoraphobia,
anticipatory
anxiety,... PREMATURE NOSOLOGIZATION

Aspecific, stress related symptoms


(depressed mood, loss of pleasure, insomnia, anxiety, tiredness,...

14