Diagnostic approaches applied in psychiatry are often criticized and deemed unsatisfactory because of their relative lack of reliability and validity. One reason for this complexity lies in the purely symptomatic approach to diagnosis. This approach also results in misdiagnosis, difficulties and high risk of aberrant therapeutic choices. The problem is also the source of great difficulty in differentiating the normal from the pathological in situations of emotional and psychological distress that should not be the subject of a psychiatric diagnosis.

1. Transdiagnostic approach in psychiatric and
related disorders
Dr Daniel SOUERY
PsyPluriel
Laboratoire de psychologie médicale, ULB
Bruxelles

2. « Disclosure »
• 2017-2019
• Financial support for research projects
– Lundbeck
– Fondation Roi Baudouin
– Fondation Roger de Spoelberch
• Advisory boards
– Janssen, Lundbeck
• No conflict of interest related to this communication

3. Content
• Introduction
– Unmet needs and limitations in psychiatric diagnoses
• Transdiagnostic approach
– A taste of ongoing research and findings
– Brain circuits and emotional pathways in the brain
• The link between psychiatric symptoms and emotions
• The example of bipolar disorders
– Cortico-limbic dissociation
• Concluding remarks
Emotions…emotions…emotions

4. Introductory remarks (1)
• Modern psychiatry is based on the principle that mental
disorders are separate categories with distinct etiologies and
clinical presentations.
• Many individuals show clear signs of general psychopathology
but do not fit precisely within the boundaries of any
diagnostic categories.
• Comorbidity (the coexistence of two or more disorders) is the
rule rather than the exception in mental health,

5. Introductory remarks (2)
No clear-cut boundaries between the different categories
Diagnostic Statistical Manual of Mental Disorders (DSM)
“there is no assumption that each category of mental
disorder is a completely discrete entity with absolute
boundaries dividing it from other mental disorders”

6. Introductory remarks (3)
• In the absence of a pathological marker, the current
definitions of mental illnesses are syndromal and are based
on a convergence of signs, symptoms, outcome, and patterns
of familial aggregation
• Many of the symptoms of mental illness are on a continuum
with normality.
– The dysphoric mood of depressive illness shares many features with the
normal sadness. At what point does such normal sadness become a form of
psychopathology?

7. Introductory remarks (4)
• Thresholds based on
– duration (such as dysphoria that persists for more than 6
months after a personal loss)
– severity (such as inattentiveness that interferes significantly
with school performance)
• Boundaries of convenience that permit “reliable”
definition,
• No inherent biological meaning and imprecise

8. “Contemporary psychiatry studies mental illnesses as diseases that manifest
as mind and arise from brain”
“The aberrations of mental illnesses reflect abnormalities in the brain/mind’s
interaction with its surrounding world; they are diseases of a psyche (or
mind) that resides in that region of the soma (or body) that is the brain.”
SCIENCE VOL. 275 14 MARCH 1997

9. How the brain learns to link a response to a stimulus.
• Relations between emotions, memory, and the brain
• Insight into the neural substrate and mechanisms of
psychiatric disorders and exploring the neuroanatomy of
emotions
• Exposure to an aversive experience
– lays down powerful memory traces that are difficult to extinguish,
– stored in a circuit in which the amygdala plays a central role, but that
has thalamic, hippocampal, and cortical components.
– memory traces, if reactivated by appropriate signals, will produce the
characteristic negative emotional tone.
J. E. LeDoux, Sci. Am. 6, 50 (June 1994); M. Davis, Annu. Rev. Neurosci. 15, 353 (1992).

10. How the brain learns to link a response to a stimulus.
• There appear to be two parallel tracks for processing
emotional stimuli:
– Fast track : subcortical regions (the thalamus and amygdala) with
rapid but relatively crude responses
– Slower track : more refined identification of features and formulation
of plans and includes the prefrontal cortex . The hippocampus also
plays a role by assessing contextual cues.
– The molecular mechanism for the formation of emotional memories
appears to involve glutamatergic activation of NMDA receptors .
J. E. LeDoux, Sci. Am. 6, 50 (June 1994); M. Davis, Annu. Rev. Neurosci. 15, 353 (1992).

11. • Hypothetically, negative emotional memories are a “trait” that is always
present
– activation leads to the clinical state,
– suppression or modulation (either by pharmacotherapy or psychotherapy) leads to
remission of symptoms.
• Drevets et al. found increased activity in
the left amygdala in both active and remitted
depressives,
• but only the active depressives had increased
left frontal activity, which suggests that the
prefrontal-amygdala pathway may be activated
during the depressed state.
How the brain learns to link a response to a stimulus.
W. C. Drevets et al., J. Neuroscience 12, 3628 (1992)

12. Tyng Chai M. et al. Front. Psychol., 24 August 2017
Figure adapted from (Panksepp and Solms, 2012)].

13. DepressionDepression
Bipolar
disorders
Bipolar
disorders
AddictionAddiction
ADHDBorderline
OCDOCD
Anxiety
disorders
Anxiety
disorders

14. DepressionDepression
Bipolar
disorders
Bipolar
disorders
AddictionAddiction
ADHDBorderline
OCDOCD
Anxiety
disorders
Anxiety
disorders

16. Common neurobiological substrate
• Depression, Bipolar disorders, addiction, OCD, anxiety
disorders, schizophrenia, …
• Transdiagnostic markers, signature
• Transdiagnostic factor reflecting general psychopathology
– Shared neural substrate across psychopathology
• Diagnosis specific features for each disorder
• Marker of familial vulnerability to psychopathology

17. Shared patterns of decreased gray matter from morphometry meta-analysis
SCZ, BPD, MDD, OCD, SUD, ANX
• (A) Results are from patient vs healthy
participant comparisons for studies pooled
across all diagnoses
• (B) separately by psychotic or nonpsychotic
diagnosis studies
• (C) and from a conjunction across the
psychotic and nondiagnosis diagnosis group
maps in panel B.
• Results show common gray matter loss across
diagnoses in the anterior insula and dorsal
anterior cingulate (dACC). The z score is for
the activation likelihood estimation analysis
for gray matter loss.
Goodkind M, Eickhoff SB, Oathes DJ, et al. Identification of a common neurobiological substrate for
mental illness. JAMA Psychiatry. 2015;72(4):305–315.

18. • Relationship between the volumes of these regions and
emotional perturbations
• Role of the anterior insula and dACC in emotional processing
and their abnormal activation during affective tasks in at least
some of the assessed disorders.
dACC: dorsal Anterior Cingular Cortex

19. Conceptual paradigm shift
• Phenotypic differences between diagnoses are negligible ?
 Model that emphasizes the importance of shared endophenotypes across
psychopathology, which is not currently an explicit component of
psychiatric nosology.
 Although this shared neural substrate suggests common brain structural
changes at some level, it is likely that these changes reflect a diverse set
of etiologies… and clinical presentation.
Goodkind M, Eickhoff SB, Oathes DJ, et al. Identification of a common neurobiological
substrate for mental illness. JAMA Psychiatry. 2015;72(4):305–315.

20. Common neurobiological pathways
• Functional connectomic signature
– features of connectome functioning commonly disrupted
across distinct forms of pathology
– Different properties of network connectivity preferentially
disrupted across type of symptomatic phenomenology
• Scaling with clinical severity,

21. DepressionDepression
Bipolar
disorders
Bipolar
disorders
AddictionAddiction
ADHDBorderline
OCDOCD
Anxiety
disorders
Anxiety
disorders

22. Emotions…emotions…emotions
 The link between “ psychiatric” symptoms and emotions
 At the heart of symptomatic productions
 Emotional Instability and emotional hyper-reactivity
 “CORTICO-LIMBIC” mis-communication
• Neurological substrate of emotions and
associated behaviors
• Emotional disturbances and early detection

23. Emotions and feelings
• Emotions: brief affective reactions that our organism produces in
response to internal or external events
– Behavioral expression, reactive and dynamic dimensions (Latin
Etymology motio, "movement")
• More stable affective attitude
• Subjective representation of emotions
• Persistent and conscious feeling
–Joy, enthusiasm, euphoria, sadness,
anger, rage, jealousy, hatred, fear,
anguish,...

24. • Spinoza (1632-1677) is thoroughly relevant to any discussion
of human emotion and feeling.
• Spinoza saw drives, motivations, emotions, and feelings an
ensemble he called affects as a central aspect of humanity.
• Joy and sorrow were two prominent concepts in his attempt
to comprehend human beings and suggest ways in which
their lives could be lived better.
Looking for Spinoza. Antonio Damazio. The NY Times Feb
2003
Emotions and philosophy

25. Antonio Damasio
“Explaining the biology of feelings and their
closely related emotions is likely to contribute to
the effective treatment of some major causes of
human suffering, among them depression, pain,
and drug addiction”

26. Emotions:
The missing link between mind and brain
• Emotion and related reactions are aligned with the body,
feelings with the mind.
• The investigation of how thoughts trigger emotions and of
how bodily emotions become the kind of thoughts we call
feelings provides a privileged view into mind and body, the
overtly disparate manifestations of a single and seamlessly
interwoven human organism.
Looking for Spinoza. Antonio Damazio. The NY Times Feb 2003

27. The example of bipolar disorders
• Mood swings exceed in intensity or duration those of normal mood and
cause alterations in functioning or suffering
• Completely out of the ordinary character of the inner states felt during
depressive or manic states
– Much further than ordinary mood swings and the "ups and downs"
that everyone has been able to cross
• Testimonies of great human value and
essential to understanding the disorder
• Patient testimonials!!!

28. The model of emotional and affective hyper-reactivity
"Upstream of manic and depressive phases"
"Emotional tsunami"
"My mental epilepsy"
"Emotional fires"
"Emotional lifts"
"I react to the quarter turn"
"it goes up very fast, very strong"

30. Prodromes of bipolar disorder
o Cohort studies of children of people with Bipolar dsiorders1
o Studies in bipolar disorder at very early onset (15-25 y)2
o Specific features? Sensitive?
o Prodromes present in the majority of patients (> 75%)
o Attenuated forms of bipolar disorder
o Personality disorders in particular “cyclothymia”
o Behavioural disorders
o Sleep disorder
o Leaking ideas and driving agitation
o Depressive tendencies, anxiety
o Irritability, anger
o Instability and mood swings (89% specificity)
1
Howes et coll. Psychol Med . 2011 August ; 41(8): 1567–1577
2
Geoffroy, Leboyer et Scott. Encéphale 2015 Feb;41(1):10-6

31. Better understand... and treat bipolar disorder
• « Mood stabilization »
– upstream of the current conception of prevention of manic or
depressive recurrence
– On the "volatility" of the system and its potential to "burst into
flames”
• Requires a good definition of emotional instability as a
"signature" of the bipolarity
»Evaluation of therapeutic approaches
–Acting on emotional instability

32. ANTICONVULSIVANTS
 Blocking of sodium channels
 Sodium channels promote the
propagation of the electrical impulse.
 Calcium channels allow the release
of neurotransmitters in the Synapse
 Increased GABA concentration by
inhibiting the enzyme GABA
transaminase, responsible for the
degradation of GABA
 "up-regulation" of GABA receptors

33. Revised objectives
« Mood stabilizers »
• « Calming the system »
• Stability and balance of emotional processes could be
markers or predictor of good response to mood stabilizers
and prevention of depressive and manic states
• Pharmacological and/or psychological approaches
• Hypothesis to be tested experimentally in
bipolar disorder
• Emotional instability as a prodrome to be

34. Brain areas involvedBrain areas involved
in emotionsin emotions
Involvement of
different
interconnected
structures to
generate, become
aware of emotions
and produce
adequate reactions

38. dlPFC: dorsloateral prefrontal cortex; vlPFC: ventrolateral prefrontal cortex; mdPFC: mediodorsal prefrontal cortex; ACC: anterior cingulate cortex
Brain mapping of structures and circuits involved in the management of emotions

39. Strakoski et al. Bipolar Disord. 2012 Jun; 14(4): 10.1111/j.1399-5618.

40. "Individuals with addictive disorders suffer in the extreme
with two basic aspects of human nature. They cannot control
their emotions and they cannot control their behaviors. They
either fell too much or they fell too little; they are over
controlled or they are out of control..... According to this
hypothesis, drug abuse begins as a partially successful
attempt to assuage painful feelings."
Professeur Edward Khantzian
Harvard Medical School of Psychiatry

41. Depressive
disorders
Bipolar
disorders
Addiction
ADHD
Borderline
OCD
Anxiety
disorders
….
Symptoms

42. • Neuroscience is finally interested in the neural substrate of emotions
 Instability felt and observed emotionally
or... communication difficulties in the "emotion-rational"couple
Emotional instability as a prodrome to detect and treat

•Cortico-limbic dissociation
The brain circuits involved in the phenomena of emotional instability or
emotional hyper-reactivity are better known in psychiatric disorders
Form of neural instability
Emotions and the brain

43.  Restoring a harmonious Fronto-limbic communication
 Do the current treatment options allow them?
 Have they been tested in this "indication"?

44. • Understanding the nature of
vulnerabilities across psychiatric
disorders may be important in
informing the development of
transdiagnostic interventions aimed
at decreasing risk of
psychopathology across disorders
• The term “transdiagnostic” can be
used to mean “across diagnoses” as
well as “above and beyond”
diagnosis
• Across different psychiatric
disorders: a transdiagnostic
signature of psychiatric illness

45. Thanks for
your attention