Download Depression

Examples of Taxonomy gone mad-DSM5:
Illustrations from mood disorders and the teenage brain
Professor Gin S. Malhi
CADE Clinic, Royal North Shore Hospital
Department of Psychiatry,
Sydney Medical School
University of Sydney
Australia
Executive Director
CADE Clinic and ARCHI Facility
University of Sydney
Director, Mood Disorders Unit
Northside Clinic
www.cadeclinic.com
CADE Clinic: Royal North
Hospital
CADE Clinic
Clinical Assessment Diagnostic Evaluation
What are the mood disorders?
• Many symptoms
• Focus on mood, emotions, feelings
Looking at one dimension
Sadness
Depression
But mood varies
Happiness
Sadness
Depression
Depression can occur from any starting
point
Normal Mood
Depression
Spectrum of Emotions
Anger
Depression
Apathy
Grief
Irritability
Boredom
Anxiety
Sadness
Happiness
Exhilaration
Fear
More complex emotions as well?
Guilt
Shame
Hurt
Critical
Hostile
Proud
Trusting
Thoughtful
Confused
Inadequate
Overwhelmed
Reality of Emotions
Reality of emotional experience
Landscape of the mind
Art from Adversity A. T. Naylor 2013,
Diagnosis of Bipolar Disorder:
Who is in a mixed state?
Malhi GS. Lancet May 2013 1599-1600
DSM5 - Diagnosis of Bipolar
Image from:
http://www.newgrounds.com/art/view/misterhe
rbal/bipolar-disorder
Other examples?
• SAD – schizoaffective disorder?
• Mixed anxiety and depression?
OK but is this depression - bipolar?
Or is it personality?
mania (BP-I)
hypomania (BP-II)
major depression
BP-II depression
BP-I depression
How can we distinguish Bipolar mood
changes from Borderline changes in affect?
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
Distinguishing Bipolar Disorder
Clinical Mood
Emotions & Feelings
Mood
Affect
Temperament
Affect:
Seconds &
Minutes
Mood:
Hours & days
Temperament:
Years & decades
EMOTION.
CADE CLINIC
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
EMOTION.
CADE CLINIC
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
APPRAISAL.
CADE CLINIC
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
RESPONSE.
CADE CLINIC
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
REGULATION.
CADE CLINIC
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
ARCHI
Advanced Research Clinical High-field Imaging
3 Tesla
Siemens Trio
Long Bore
Dedicated
Research Facility
• Spectroscopy
• Structural and
Functional MRI
•
•
•
•
Siemens 3Tesla Trio
Hypothesis
• Hypothesis:
• Fronto-Limbic Network (FLN) disturbances:
• Vicissitudes of mood and affective lability characterize BD and BPD respectively.
• Within FLN there are key regions of interest in emotion
processing and regulation:
– dorsolateral, ventrolateral and dorsomedial prefrontal cortices
(dl-PFC, vl-PFC, dm-PFC) &
– limbic structures such as the amygdala (Ag) and hippocampus
(Hi)
Method
• Aim: To determine the differences between
BD and BPD in engaging the FLN:
– Used emotional Stroop (eStroop) task and
examined changes with fMRI (requires inhibition
of interference from emotional stimuli).
• Also investigated
– whether any differential neural responses could
explain differences in the clinical symptomatology
of the two disorders.
Interference Effect
•
•
•
•
•
•
Green
Orange
Red
Blue
Brown
White
Colour Stroop
•
•
•
•
•
•
Blue
Red
Brown
Green
White
Orange
E-Stroop
Suicide Injection Death Medication …. Table House Napkin Catch
N
A
N
A
N
A
A
N
Blocked Design
N
A
8 words and duration 16 sec.
Six blocks of each valence
alternating with baseline blocks
of non-words (****) - 2
functional runs.
Each word for 1500ms, + 500ms
(250-750ms) inter-stimulus
interval (black screen).
Words not repeated & order of
blocks was counter-balanced.
Accuracy and speed
300 Blocks (150 Affect vs. Neutral)
10 stimuli/block
Each block = 30 sec
Individual stim presentation = 3 sec
Response button feedback
BPD=13
BP=16
HC=14
Analysis: GLM
Questionnaires
• On mood, emotion regulation, childhood trauma and schemas
– 1) Depression Anxiety Stress Scales1 (DASS);
– 2) Difficulties in Emotion Regulation Scale2 (DERS);
– 3) Emotion Amplification and Reduction Scale3 (TEARS);
– 4) Childhood Trauma Questionnaire4 (CTQ);
– 5) NEO Five-Factor Inventory5, 6 (NEO-FFI) which measures
the five main domains of personality.
– Participants were also administered the Weschler Test of
Adult Reading7 (WTAR) as a measure of premorbid
intelligence.
Demographic & Psychological Data
BPD
BD
Healthy Controls
Mean (SD)
Mean (SD)
Mean (SD)
32(7.9)
35.6(10.7)
31.2(11.1)
F(2,40) = .84
0.439
14.6(2.4)
15.9(1.5)
15.4(1.9)
F(2,39) = 1.44
0.249
1.4(1.2)
1.6(1.1)
0(0)
F(2,42) = 11.47
0.000
116(5.8)
117(6.9)
117(5.7)
F(2,38) = .16
0.376
54.8(6.7)
55.4(8.5)
51.3(7.0)
F(2,37) = .86
0.755
DASS Total Score
26.5 (12.4)
15.0 (9.7)
6.8 (5.1)
F(2, 40) = 14.33
0.000
DASS Depression
9.7 (6.7)
4.4 (4.8)
2.1 (2.7)
F(2, 40) = 8.26
0.000
Neuroticism
38.1(8.9)
30.6 (4.8)
17.4 (6.2)
F(2, 37) = 25.56
0.000
130.0 (18.6)
89.6 (19.6)
68.8 (17.5)
F(2, 40) = 37.9
0.000
37.6 (7.7)
43.8 (6.9)
47.8 (7.6)
F(2, 40) = 6.61
0.003
Statistics
Measure
Age (years)
Years of Education
Number Psychiatric
Meds
WTAR Standard
Score
CTQ (Total Score)
F-Statistic
p-value
Questionnaires
DERS Total Score
TEARS Total Score
Borderline and Bipolar
Malhi et al. 2013. Molecular Psychiatry
•Key findings from our a
priori regions of interest
analyses: compared to HC
–both patient groups
displayed a similar
pattern of change
involving the lateral
PFC,
•a reduction of
neural activity in
the left dl-PFC and
a concomitant
increase in activity
in the right vl-PFC,
Borderline and Bipolar
Malhi et al. 2013. Molecular Psychiatry
•Key –No
findings
sig. from
differences:
our a
priori regions
•Reaction
of interest
Time or
analyses: compared
•Response to HC
Accuracy
–both patient groups
displayed
–But
a divergent
a similar
pattern of change
neural
involving the lateral
activity
PFC, •involving
•a reduction of
neural
activity
activity
in BD
in
•the
and
left
diminished
dl-PFC and
a concomitant
Ag
activity in BPD.
increase in activity
in the right vl-PFC,
Borderline and Bipolar
Greater emotion regulation difficulties associated with:
lower activation in the left dl-PFC (b = -153.61), and
greater activation in right vl-PFC (b = 81.27) Greater
emotion regulation difficulties
Borderline and Bipolar
• Novel group comparison study using fMRI and
emotional Stroop (needs replication)
•
•
•
•
dm-PFC activation was increased in Bipolar
Ag activity was decreased in Borderline
Correlation of lateral PFC activations with DERS.
Increased vl-PFC activity and decreased dl-PFC
activity in our patients, indicates greater
difficulties in regulating emotion.
Left Fronto-Parietal
(LFP)
Right Fronto-Parietal
(RFP)
Anterior Default Mode
(ADM)
Posterior Default Mode
(PDM)
Fronto-TemporoParietal
(FTP)
Ventral DefaultMode
(VDM)
VDM
RFP
This network has
been suggested to
play a role in
maintaining the
integrity of the self,
dysfunction in this
network has been
linked to self
monitoring deficits.
vMPFC
vMPFC has been
associated with
automatic affective
processing.
FTP
vLPFC
vLPFC, dMPFC,
TPJ have been
suggested to be
involved in theory
of mind
processes.
ACC
dMPFC
ACC, TPJ have
been suggested
to play a role in
reflected selfappraisal
TPJ
ADM
PDM
pC is suggested
to be involved in
the integration of
multiple neural
systems
producing a
conscious selfpercept and also
to modulate
conscious
processing.
The cortical
midline structure
of this network
has been
associated with
self-referential
processing and
social cognition
pC
BPD < HC / BD
BD > HC / BPD
Flying ‘High’…… as a Kite
But Bipolarity often begins life as Depression
mania (BP-I)
hypomania (BP-II)
major depression
BP-II depression
BP-I depression
But then what comes before depression?
Royal North Shore Hospital
(02) 9926-7746
www.cadeclinic.com.au
013. http://dx.doi.org/10.1016/j.biopsych.2013.01.030
Girls Study
PARTICIPANTS
58 Adolescent girls aged 14-16 years
Exclusion criteria
Neurological event (eg, Traumatic Brain Injury, LOC,
Epilepsy/Seizures)
Learning or Developmental Disorder
Any medical or physical condition that precluded Neuroimaging
Girls Antecedents Study
PROCEDURE
i) Self-report questionnaires
Personality, Coping, Self-Concept, Emotional Dysegulation,
Mood, Anxiety, Eating Disorders, Psychosis, Substance Use,
ADHD, Learning/Behaviour
ii) Computerised neuropsychological tests (CogState)
Memory, Attention, Processing speed, Executive functions, Social
cognition
iii) Neuroimaging
Structural, functional and resting state acquisitions
Girls Study
GROUP ASSIGNMENT
Adolescents were assigned to one of two groups according
to presence or absence of sub-clinical Emotional Symptoms
(ES+ and ES-)
Defined by exceeding the cut-off score for one or more
disorders assessed by the Child and Adolescent PsychProfiler (CAPP) e.g.
Dysthymic Disorder
Anxiety Disorders
Girls Study
Domain
ES+
ES-
Sig.
Mood and Anxiety
Depression (CDI)
<0.0001
State Anxiety (STAI)
0.007
Trait Anxiety (STAI)
<0.0001
Personality (NEO-FFI)
Neuroticism
<0.0001
Extraversion
0.044
Conscientiousness
0.002
Emotional Dysregulation (DERS)
<0.0001
Self-Concept / Self-Esteem (Piers-Harris)
Intellectual Abilities
<0.0001
Physical Appearance & Attributes
0.002
Popularity
0.05
Strongest clinical predictors of ES+
Trait Anxiety was the strongest predictor of ES+.
No other measure significantly contributed to the model.
Imaging Design
• Series of 60 IAPS images with standardized negative,
positive and neutral affect presented on screen in 20
second blocks
– 5 images per block, 2 blocks for each emotional valence
per run
• Interspersed with baseline blocks of greyscale blank
images (6 blocks per run)
– over two runs, each with a duration of four minutes.
• Participants were asked to label valence of emotional
images via button press.
Study Paradigm
Bipolar Patients
Cluster
MNI co-ords
voxel
Size
x,y,z (mm)
equivZ
Regions
Healthy Controls (HC) vs Bipolar Patients (BD)
HC> BD
Frontal regions
dl-PFC extending to
vl-PFC
274
-30, 46, 18
2.56
dlpfc
63
-36, 44, 40
2.11
159
-16, 44, 30
2.7
115
12, 50, 30
2.61
73
48, 36, -12
2.29
BD> HC
Frontal regions
m-PFC
vl-PFC
Borderline
Cluster
MNI co-ords
voxel
Size
x,y,z (mm)
equivZ
Regions
Healthy Controls (HC) vs Borderline Patients (BPD)
HC> BPD
Frontal regions
dl-PFC
409
-32, 34, 34
3.11
143
32, 40 36
2.26
100
26, -8, -14
2.73
99
44, 38, -8
2.68
284
-44, 38, -6
2.32
Limbic regions
Ag/Hippocampus
BPD> HC
Frontal regions
vl-PFC
In Conclusion
• Phenotypic description based on phenomenology
alone remains challenging and imprecise
• Necessary to deconstruct bipolar disorder
clinically and scientifically
• Neural markers may assist in partitioning
disorders/subtypes
• Neural antecedents to mood disorders are likely
to emerge early and can be potentially detected
to identify those likely to develop disorders later
in life
Acknowledgements
• Dr Pritha Das – neuroimaging analysis
• Dr Carissa Coulston & Dr Kristina Fritz – statistical analyses
and neuropsychological testing
• CADE Clinic - Clinical & Research Team
– Danielle Bargh & Michelle Tanious
• Professor Vince Calhoun (Unversity of New Mexico, USA)
• Professor Luan Phan (University of Illinois, USA)
Thank you for kind
attention
References:
Malhi GS. (2013) Diagnosing Bipolar Disorder: Who is in a mixed state? 381, 1599.
The Lancet,
Malhi GS, et al. (2013) Differential engagement of the fronto-limbic network during
emotion processing distinguishes bipolar and borderline personality disorder. (doi:
10.1038/mp.2013.22).
Molecular Psychiatry
Das P, Coulston C, Bargh D, Tanious M, Phan L, Calhoun V, and Malhi GS. (2013)
Neural Antecedents of Emotional Disorders: An fMRI Study of Subsyndromal
Emotional Symptoms in Adolescent Girls. (doi.org/10.1016/j.biopsych.2013.01.030).
Biological Psychiatry.
THE “BIPOLAR SPECTRUM” – Cross-sectionally
Classic spectrum of ‘mood’
Mood changes are continuous:
– no discrete entities in reality
– mood connects unipolarity and bipolarity.
increasing features of elevation
unipolar
bipolar
MDD
CADE CLINIC
BD-NOS
Royal North Shore Hospital
(02) 9926-7746
BD-II
BD-I
www.cadeclinic.com.au
Diagnosis of Bipolar Disorder:
Who is in a mixed state?
Malhi GS. Lancet May 2013 1599-1600