Borderline Personality Disorder: From Brain to Mind…

B.Grosjean.MD.Harbor UCLA.Grand Round

2-7-2006.

Psychotherapy

Theory of mind

Genetic Cognition

PTSD

GlutamatePharmacotherapy

Education

Psychoanalysis

NMDA

PCP 5HT

Psychopathology

Attachment Theory

Emotion

Dissociation

Neuroimaging

Molecular biology

Learning theory

Borderline Personality Disorder

Mind

Brain

Borderline Personality Disorder

Epidemiology

Prevalence:• 1-2% general population (USA).• 71-73 % women

Up to 10% of psychiatric outpatients and 20% of inpatients.

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)

Behavioral/ affect regulation/CognitionPerceptual Alteration

Borderline Personality Disorder Diagnosis

Poor affect regulationPoor impulse controlUnstable relationshipsRisky behaviors (substance

abuse etc…)Suicidality, self harm

Borderline Personality Disorder 1- Behavioral Symptoms

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.

Borderline Personality Disorder 2- Cognition

Fonagy,Bateman 1995,2004

Posner 2002,Lezenweger 2004;Fertuck 2005.

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.

Borderline Personality Disorder 3- Perceptual alterations

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

Treatment ?

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 years60-75% after 20 y F/u no longer meet criteria for BPD9% completed suicide

BRAIN

• 100 billion neurons

• Each develops between 1,000 to 10,000 connections with other neurons

Geography of the brain

Right and Left

Right hemisphere

(develop before left): Holistic non verbal, music visual Face recognition ambiguity empathy autobiographical memory

integrated map of the body

Left Hemisphere: Linear processing Linguistic Logical-syllogistic reasoning Literal brings cohesion (not

coherence) to “make sense” (integration) needs communication with Right Hemisphere/corpus callosum.

Corpus Callosum“INTEGRATION”

• largest white matter structure in the mammalian brain

• connects the left and right cerebral hemispheres.

Hippocampus“PUZZLE ASSEMBLER”.

• Essential role in the formation of new memories (episodic or autobiographical/ EXPLICIT)

• required for simple spatial memory tasks .

Amygdala“EMOTIONAL BRAIN”

• Key role in the emotions (fear pleasure).

• Key role in implicit, emotional memories: interprets the emotional significance of the experience.

Memory

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

• 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.

Anterior Cingulate Cortex“Conflict monitoring”

Pre-frontal cortex

Body regulation Emotional regulation Attunement Response Flexibility Empathy Fear Extinction Intuition Morality Self-Knowing Awareness

Medial Prefrontal Cortex

Activated by observation of social interaction

Activated during mentalization Activated with meditation, body

exercises, prayer Size correlate with degree of

meditation ?

NEUROPLASTICITY

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.

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.

Neurotransmission

• Serotonin: impulsive aggression, working memory and inhibitory processes

• Dopamine: emotional regulation, motivational systems, and cognitive perceptual phenomenon.

Glutamate

• Primary excitatory neurotransmitter in the mammalian brain.

• Involved in many CNS mechanisms of plasticity including those contributing to learning and memory.

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”.

NMDA Receptors

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.

Mirror Neurons

The Miracle ?

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

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.

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

MIND 1

The mind develops as the genetically programmed maturation of the brain responding to ongoing experiences.

D.Siegel. “The Developing Mind” 1999.

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.

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”.

MIND

Siegel (2001) propose as the qualities that foster secure attachment:

CollaborationReflective dialogueRepairCoherent narrativesEmotional communication

BETWEEN BRAIN AND MIND

Emotion

Mentalization

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

Emotions

Emotional expression allow the rapid communication of information between individual.

They can be viewed as reinforcers that modulate a particular behavior.

Mentalization

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.

What prevent acquisition of mentalization ?

• Genetic?• Toxic environment ?• Trauma• Neglect• Chaos

• 906,000 children victims of abuse or neglect in 2003. (1.24% of general population).

• Neglect: 60 %;Neglect: 60 %; physical abuse19%; sexual abuse 10 % ; emotional abuse 5 % : "other“ 17%.

• Children ages birth to 3 yearsbirth to 3 years had the highest highest rates of victimizationrates 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

The Challenge

• 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.

Bruised brains aching minds Developmental Effects of Child Abuse and Neglect

Bruised brains aching minds Developmental Effects of Child Abuse and Neglect

• Overwhelmed hippocampus is unable to process explicit memory

• Implicit recollection w/o explicit processing maybe the source of flashback.

Maltreated children have multiple problems:– Isolation, hence fewer non parental model of

emotional communication.– Difficulties in recognition, expression and

understanding of emotions (Camras et al 1996).– partial and temporary collapse of mentalization

(Allen 2001).

• Neglected children have difficulties to discriminate between angry, sad and fearful expression

• Physically abused children have difficulties recognizing sadness and disgust but not anger.

• Both have trend to perform better than control children in detecting masked expressions of emotions and a bias (increased accuracy) toward detection of threat related information such as anger.

Recognizing emotion in faces: Developmental Effects of child abuse and neglect”. Pollak, et al.2000.

Treatments ?

Basics !!!!

GeneticPrenatalEarly lifeChildhoodTeenagerAdulthood

Prevention/education/social supportPrevention/education/social supportPrevention/education/social supportPrevention/education/social supportPrevention/education/social supportPrevention/education/social support

Importance of early intervention.

• Effectiveness of home visiting (6.5 during pregnancy) by nurses.

• Outcome: at 6 months of age, nurses-visited infants born to women with low psychological resources, in contrast to their control group had:– less emotional vulnerability– higher emotional vitality – At 21 month they were less language delays.

Home Visiting by Paraprofessionals and by Nurses: a Randomized, controlled Trial. Olds et al; Pediatrics 2002.

“When neurons fire together , they wire together” (Donald Hebb).

Experiences turn on the genetic machinery and through the synthesis of new proteins, change and/or create internal connections in the brain.

From Brain…

In therapy: new learning is verbal (symbolic) and non verbal (emotional).

While treating patients with a very poor quality of attachment history (difficulties at emotional and mentalization level), it is crucial to pay great attention to the “attachment quality” of the therapeutic relationship (collaboration; repair; coherent narratives; emotional communication)

…to Mind

Traditional psychotherapy have focused on changes related to the interplay between emotions and thoughts.

Most therapies have essentially ignored changes related to bodily states.

Neurobiology indicate how a global approach (including physical well being) of the person is essential for improving general condition.

BPD from Brain to Mind…

Emotion dysregulation Dissociation Identity diffusion Emotion expression Cognitive dysfunctions Mentalization deficit Learning problems Memory problems

HPA hypereactivity Slow return to baseline

Comorbid: depression, substance abuse dependence

Stable attachment; lower level of stress

Education; skills training

Integration of body well being

Diversification of emotion expression, learning cues

Reactivation of old patterns and re-creation of autobiographic narrative that make sense and authorize integration

Increase self awareness and symbolization capacity

Genetic vulnerability

Neurobiological vulnerability

Chaos Neglect Abuse Chronic stress

• PROVIDE STRUCTURE. • RELIABLE AND CONSISTENT:

– Doing what you have agreed to do– Avoid expression of extreme emotions– Inquisitive and curious rather than aloof and

single minded– Simple rather than clever.

• ABLE TO DECREASE AROUSAL (calm under fire, be matter of fact).

• HELP PATIENTS TO VALIDATE THEIR OWN EXPERIENCES.

• ACCEPT THAT YOU MAKE MISTAKE AND RECOGNIZE ENACTMENT.

“A fragile ego left alone remains fragile. Medication or superficial support alone is not a substitute for the feeling that one is understood by another human being”.

“Emotion ceases to be suffering as soon as we form a clear and precise picture of it”. Spinoza.

Picture by Gregory Colbert

Thank you!

www.bgrosjean.comPicture by Gregory Colbert