Borderline Personality Disorder: From Brain to Mind…

1. Borderline Personality Disorder: From Brain to Mind… B.Grosjean.MD. Harbor UCLA.Grand Round 2-7-2006.

2. Psychotherapy Theory of mind Genetic Cognition NMDA Glutamate Pharmacotherapy Attachment Theory Education PCP 5HT Dissociation PTSD Neuroimaging Learning theory Psychoanalysis Emotion Psychopathology Molecular biology

3. Borderline Personality Disorder Brain Mind

5. Borderline Personality Disorder Epidemiology • Prevalence: • 1-2% general population (USA). • 71-73 % women • Up to 10% of psychiatric outpatients and 20% of inpatients.

6. Borderline Personality Disorder Etiopathology • Genetic Disposition/ Temperament • Pathology of early attachment: • neglect • trauma • chaotic-disorganized? • HPA axis hypersensitivity • Neurotransmitter Systems ? • ?? NMDA receptors dysfunction?? • ??? Mirror neurons dysfunction??? Inpatient BPD: 76 % reported physical abuse; 86% reported sexual abuse (26% w/o BPD)

7. Borderline Personality Disorder Diagnosis • Behavioral/ affect regulation/ • Cognition • Perceptual Alteration

8. Borderline Personality Disorder 1- Behavioral Symptoms • Poor affect regulation • Poor impulse control • Unstable relationships • Risky behaviors (substance abuse etc…) • Suicidality, self harm

9. Borderline Personality Disorder 2- Cognition Problems with: • Working memory • Autobiographical memory • Learning processes (reversal learning?) • Mentalization. • Executive functioning • Tasks that require controlled attention processing • Attentional network involved in conflict resolution and in the voluntary inhibition of thought and behavior. Fonagy,Bateman 1995,2004 Posner 2002,Lezenweger 2004;Fertuck 2005.

10. Borderline Personality Disorder 3- Perceptual alterations • Impaired emotion recognition as revealed by the impaired ability to read and/or to interpret facial expressions of emotion Donegan 2003. • Dissociation Zanarini et al 2001.

11. Borderline Personality Disorder Neuroimaging • Reduced hippocampal and amygdalar volumes. Driessen 2000;Rush 2003; Terbatz van Elst 2003. • Aberrant functioning in the cingulate cortex. Hazlett 2005 Milham et al 2005. • FMRI of BPD patients listening to scripts describing abandonment events show dysfunction of medial and dorso-prefrontal cortex. Schmal 2003. • Smaller corpus callosum in abused and or neglected children. Teicher 2003,2004

12. Treatment ?

13. Borderline Personality Disorder Validated/Manualized Treatments • Transference Focused Psychotherapy (TFP) Otto Kernberg. Object relation theory. 1967. • Dialectic Behavioral Therapy (DBT) Marsha Linehan Deficit in self regulation.1994. • Mentalization Based Treatment (MBT). Bateman, Fonagy. Deficit in mentalization processes. 2000. Medications can be an adjunction but are useless without psychotherapy. • 75% meet criteria for remission after 6 years • 60-75% after 20 y F/u no longer meet criteria for BPD • 9% completed suicide

14. BRAIN

15. 100 billion neurons • Each develops between 1,000 to 10,000 connections with other neurons

16. Geography of the brain

17. Right and Left Left Hemisphere: • Linear processing • Linguistic • Logical-syllogistic reasoning • Literal • brings cohesion (not coherence) to “make sense” (integration) needs communication with Right Hemisphere/corpus callosum. Right hemisphere (develop before left): • Holistic • non verbal, music • visual • Face recognition • ambiguity • empathy • autobiographical memory integrated map of the body

18. Corpus Callosum“INTEGRATION” • largest white matter structure in the mammalian brain • connects the left and right cerebral hemispheres.

19. Hippocampus“PUZZLE ASSEMBLER”. • Essential role in the formation of new memories (episodic or autobiographical/ EXPLICIT) • required for simple spatial memory tasks .

20. Amygdala“EMOTIONAL BRAIN” • Key role in the emotions (fear pleasure). • Key role in implicit, emotional memories: interprets the emotional significance of the experience.

21. IMPLICIT Present at birth No sense of recollection present when memories recalled and encoded Includes behavioral, emotional, perceptual, and possibly bodily memory EXPLICIT > 2 y/o Requires conscious attention Sense of recollection present when being recalled Includes semantic (factual) and episodic (autobiographical) memory Involves the hippocampus Memory

22. Anterior Cingulate Cortex“Conflict monitoring” • Vital to cognitive functions, such as reward anticipation, decision-making, empathy, and emotion. • Involved in a variety of autonomic functions (HR, BP) • responsible for rendering new memories permanent.

23. Pre-frontal cortex • Body regulation • Emotional regulation • Attunement • Response Flexibility • Empathy • Fear Extinction • Intuition • Morality • Self-Knowing Awareness

24. Medial Prefrontal Cortex • Activated by observation of social interaction • Activated during mentalization • Activated with meditation, body exercises, prayer • Size correlate with degree of meditation ?

25. NEUROPLASTICITY

26. NEUROPLASTICITY Development shapes the brain by altering the strength of synaptic connections within the brain. • synapses can be strengthened, weakened or eliminated (pruning) • new synapses can be formed in response to experience • genetic information, toxic substance, and stressful or absent experience can lead to elimination of synapses.

27. Brain growth spurt in humans between the last 3 months of pregnancy and extends into the first 3 years of life. Major Pruning end around the end of puberty. Adult brain remains plastic during the entire life.

28. Neurotransmission • Serotonin: impulsive aggression, working memory and inhibitory processes • Dopamine: emotional regulation, motivational systems, and cognitive perceptual phenomenon.

29. Glutamate • Primary excitatory neurotransmitter in the mammalian brain. • Involved in many CNS mechanisms of plasticity including those contributing to learning and memory.

30. N-methyl-D-aspartate subtype glutamate receptors (NMDARs) • Concentrated in the hippocampus, forebrain, amygdala, caudate, putamen and thalamus (rodents) • NMDAR, can “detect” the coincidence of 2 events, so called “associativity”.

31. NMDA Receptors

32. NMDARs • Hypofunctioning of the NMDAR, causes learning impairment, memory impairment (working memory) and dissociation. • Overactivation of NMDA receptor via the glutamate site results in neurotoxicity and cell death.

33. Mirror Neurons

34. The Miracle ?

35. Mirror Neurons A class of neurons that discharge not only when a monkey executes goal-related hand action, but also when observing other individuals executing similar actions. Gallese, Rizzolatti et al. 1996

36. Mirror Neurons Empathy “Einfühlung” • Iacoboni proposes that the human mirror neuron system, in concert with the limbic system, play a major role in the process of understanding the emotion and intention of other people…and would be at the origin of empathy. • To empathize, we need to invoke the representation of the actions associated with the emotions we are witnessing.

37. Mirror Neurons Empathy “Einfühlung” • fMRI study showed that same brain region are activated while observing an emotion or during the imitation of the emotional face expression • These data suggest that we understand the feelings of others via a mechanism of action representation, so we build our empathic resonance in the experience of our acting body and the emotions associated with specific movements . “Neural mechanisms of empathy in human: a relay from neural systems for imitation in limbic area” Carr, Iacoboni et al 2003

39. MIND 1 The mind develops as the genetically programmed maturation of the brain responding to ongoing experiences. D.Siegel. “The Developing Mind” 1999.

40. MIND 2 • Development is about the creation of specific circuits, not merely the overall amount of synapses in the brain. • The ways in which the circuits regulating emotional and social functioning develop is profoundly influenced by interpersonal experience beginning early in life.

41. MIND 3 Attachment researches indicate that “good attachment relationship are likely to promote the development of integrative capacities of the brain in enabling the acquisition of emotional, cognitive and interpersonal abilities”.

42. MIND Siegel (2001) propose as the qualities that foster secure attachment: • Collaboration • Reflective dialogue • Repair • Coherent narratives • Emotional communication

43. BETWEEN BRAIN AND MIND Emotion Mentalization

44. Emotions “Facial expression are a crucial component of human emotional and social behavior and are believed to represent innate and automatic behavior patterns”Darwin 1872

45. Emotions • Emotional expression allow the rapid communication of information between individual. • They can be viewed as reinforcers that modulate a particular behavior.

46. Mentalization

47. Mentalization • Ability to read the expression on another’s face and know what this person is feeling. • Ability to represent the mental states of others, i.e. their thoughts, desires, beliefs, intention and knowledge.

48. What prevent acquisition of mentalization ? • Genetic? • Toxic environment ? • Trauma • Neglect • Chaos

49. The Challenge • 906,000 children victims of abuse or neglect in 2003. (1.24% of general population). • Neglect: 60 %; physical abuse19%; sexual abuse 10 % ; emotional abuse 5 % : "other“ 17%. • Children ages birth to 3 years had the highest rates of victimization at 1.6% of the same age group. Girls were slightly more likely to be victims than boys. Child Maltreatment 2003: Summary of Key Findings National Clearinghouse on Child Abuse and Neglect Information 2005

50. Bruised brains aching mindsDevelopmental Effects of Child Abuse and Neglect • High levels of cortisol destroy synapses. • Abuse, neglect and chronic states of misattunement lead to an overpruning of synapses (R OFC) leaving individuals with impaired ability to modulate and regulate emotion in response to stress.