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London iCAAD 2019 - Daniel Souery - A TRANSDIAGNOSTIC APPROACH FOR PSYCHIATRIC AND RELATED DISORDERS

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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.

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London iCAAD 2019 - Daniel Souery - A TRANSDIAGNOSTIC APPROACH FOR PSYCHIATRIC AND RELATED DISORDERS

  1. 1. Transdiagnostic approach in psychiatric and related disorders Dr Daniel SOUERY PsyPluriel Laboratoire de psychologie médicale, ULB Bruxelles
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. Tyng Chai M. et al. Front. Psychol., 24 August 2017 Figure adapted from (Panksepp and Solms, 2012)].
  13. 13. DepressionDepression Bipolar disorders Bipolar disorders AddictionAddiction ADHDBorderline OCDOCD Anxiety disorders Anxiety disorders
  14. 14. DepressionDepression Bipolar disorders Bipolar disorders AddictionAddiction ADHDBorderline OCDOCD Anxiety disorders Anxiety disorders
  15. 15. 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
  16. 16. 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.
  17. 17. • 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
  18. 18. 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.
  19. 19. 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,
  20. 20. DepressionDepression Bipolar disorders Bipolar disorders AddictionAddiction ADHDBorderline OCDOCD Anxiety disorders Anxiety disorders
  21. 21. 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
  22. 22. 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,...
  23. 23. • 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
  24. 24. 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”
  25. 25. 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
  26. 26. 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!!!
  27. 27. 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"
  28. 28. 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
  29. 29. 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
  30. 30. 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
  31. 31. 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
  32. 32. Brain areas involvedBrain areas involved in emotionsin emotions Involvement of different interconnected structures to generate, become aware of emotions and produce adequate reactions
  33. 33. 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
  34. 34. Strakoski et al. Bipolar Disord. 2012 Jun; 14(4): 10.1111/j.1399-5618.
  35. 35. "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
  36. 36. Depressive disorders Bipolar disorders Addiction ADHD Borderline OCD Anxiety disorders …. Symptoms
  37. 37. • 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
  38. 38.  Restoring a harmonious Fronto-limbic communication  Do the current treatment options allow them?  Have they been tested in this "indication"?
  39. 39. • 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
  40. 40. Thanks for your attention

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