Cuttingedge Discoveries: Transforming Lives, Fueling the Economy

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Cutting-edge DiscoveriesTransforming
Lives,Fueling the Economy
THE INNOVATORS

• Spring 2007

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Understanding Emotional Well-BeingNeurochemistr
y May Hold the Key
THE INNOVATORS

• Jaak Panksepp, Ph.D.
• Baily Endowed Chair of AnimalWell-being Science
• Department of Veterinary and Comparative Anatomy,
  Pharmacology, and Physiology
• College of Veterinary Medicine

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The Functional Parts The Neurochemistries
The WholeMind - Brain
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Much Underutilized in Modern Psychiatry
Panksepp Bishop (1981).
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There is an impenetrable mysteryin the fact
that subjective experience exists in a
physiochemical world.
Robert Holt (1989) Freud Reappraised
A continuing dilemma for modern psychiatry. The
nature of affect is the most importantscientific
question relevant for psychiatry.
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1st Half of the 20th Century Psychiatrya Mind
with No Brain

• Functional analysis of mental apparatus
• Abundant ideas with little eventualagreement
  about fundamental issues. . .some of the ideas
  were delusional
• The mental apparatus has to beunderstood from
  the bottom-up. . . top-down. . . a combination
  of
• Functional brain research
• Cross-species evolutionary perspectives
• A mental analysis consistent with the above

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2nd Half of the 20th Centurya Brain with Little
Mind

• Diagnostics and the powerof neuroscience
  techniques
• Neuroanatomy
• Neurochemistry
• Brain imaging
• Molecular biology
• Biological psychiatry a brainwithout a
  structured mind. . .
• Neuro-evolutionary perspectivescan finally
  provide that structure!

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21st Century

• Can Biological Psychiatry and Psychoanalysis be
  brought together . . . made whole. . . again?
• Perhaps
• With a neuro-psychoanalysis that seeksto
  understand the neuro-affective natureof the
  mental apparatus

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Freuds Project

Primary-process affects
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Evolutionary Perspectives

• Neural Layering
• Mental Layering
• Affects emergedearly in evolution

Affects provide comfort zones by which all
animals live their lives.
Panksepp, J. (Ed.) (2004). Textbook of
Biological Psychiatry, Wiley
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What is the Nature of Affect?(a Rough Taxonomy)
Affects are evolved tools for living

• Pleasures pains of sensation
• Consummatory rewards,environmental punishments
• Emotional arousals
• Instinctual brain action systems
• Homeostatic drives/satisfaction
• Hunger, thirst general bodily feelings

Instinctual
The ancestral voices of the genes
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Affective Neuroscience
Instinctual
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Neo-corex is the organ of ambiguity
Basic Emotions
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AffectiveConsciousness
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Basic Emotion Systems (ESB-induced)
Emotional Endophenotypes
Panksepp (1982)
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Emotional Command or Operating Systems
7. Affect reflects the full operation of such
systems
Neural Definition of Emotional Systems
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The Core SELF

• Lowest ESB energy to obtain powerful emotional
  changes
• Smallest brain damage compromising consciousness
• Most massive convergence of brain systems

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Emotional EndophenotypesEnergetic Field-Dynamics
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Emotional EndophenotypesEnergetic Field-Dynamics
EmotionalEndophenotypes
Energetic Field-Dynamics
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Psychobehavioral Endophenotypes

• Curiosity
• Search for meaning
• Delusional connections
• Incentive salience
• Vividness of dreams

Curiosity/seeking Dopamine
Panksepp, J. (2006). EmotionalEndophenotypes in
evolutionary Psychiatry. Progress in
Neuro-Psychopharmacology Biological Psychiatry,
30 774-784.
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But how did the fox lose its fearin 20th Century
Behavioral Neuroscience ?
Ruthless Reductionism
-Mentality-
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Primary Process Affects ReflectInstinctual
Network Functions
Davis, K.L., Panksepp, J., Normansell, L. (2003)
Affective Neuroscience Personality Scales
Normative data and implications.
Neuro-Psychoanalysis, 5 57-69.
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There is an impenetrable mysteryin the fact
that subjective experience exists in a
physiochemical world.
Robert Holt (1989) Freud Reappraised
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Dual-Aspect Monism
Angry behavior reflects angry feelings
It is penetrable with modern neuroscience,
especially if other animals share the
foundational processes for consciousness for
example emotional feelings
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Playful Behavior Reflects Joyful Feelings
Rat laughter
Rough tumbleSocial play
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Concentrated in Limbic System
Grief
Joy
(peptides in blue)
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Emotional Systems Emergent Emotions Emotional
Disorders SEEKING ( -) Interest Obsessive
Compulsive Frustration Paranoid
Schizophrenia Craving Addictive
Personalities RAGE (- ) Anger Aggression Irri
tability Psychopathic tendencies Contempt Persona
lity Disorders Hatred PTSD variants FEAR
(-) Simple anxiety Generalized Anxiety
Dis. Worry Phobias Psychic trauma PTSD
variants PANIC (-) Separation distress Panic
Attacks Sadness Pathological Grief Guilt/Shame D
epression Shyness Agoraphobia Embarrassment Soci
al Phobias/AUTISM PLAY () Joy and
glee Mania Happy playfulness ADHD
Endophenotypes
Syndromes
Social bonding - autism depression
Social-engagement ADHD
(Panksepp, 1998)
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Joy
Sadness
Social play
Separation-distress
ADHD
Depression autism
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Attachment/Social Bonding Chemistries
Opioids
Social bonding may be an addictive process
Autism is a disorder of the social brain
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Endogenous Opioidsand Social Attachments

• Similarities between
• Opiate Addiction Social Independence
• Drug dependence 1. Social bonding
• Drug tolerance 2. Estrangement
• Drug withdrawal 3. Separation distress
• Psychic pain A. Loneliness
• Lacrimation B. Crying
• Anorexia C. Loss of appetite
• Despondency D. Depression
• Insomnia E. Sleeplessness
• Aggressiveness F. Irritability

People and animals seek opioidsto alleviate
affective distress
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Separation-Distress Crying System
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Separation Distress in Puppiesas a Function of
Low Opiate Doses
Panksepp, et al. (1978). Biol. Psychiatry, 9,
213-220.
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Social Bonding Maternal Chemistries
Opioids (1970s)
Oxytocin (1980s)
Prolactin (1990s)
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Damasio, et al., 2000
Illustration from Panksepp, J. (2003). Science,
Oct 10th.
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Illustration from Panksepp, J. (2003). Science,
Oct 10th.
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Grief
Joy
Anger
Fear
Damasio, et al. (2000) Nature Neuroscience, 3
1049-1056
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Opioid Excess Model of Autism

• Reduced separation-distress in autism and
  following opioids
• Reduced gregariousness in both
• Reduced pain sensitivity following both
• Increased stereotypies
• Increased rough-and-tumble play

Naltrexone (0.25 mg/kg) can reduce autistic
symptoms in about 40 of children
Panksepp (1979) Trends in Neuroscience, 2,
174-177.
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CONTACT COMFORT
Touch alleviates pain
Opioid Dyregulation
Panksepp, J. et al., (1980). Opioid blockade and
social comfort in chicks. Pharmacology
Biochemistry Behavior, 13, 673-683.
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Sadness
Separation-distress
Depression autism
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Is social motivation regulatedby endogenous
opioids?
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Tail Wags
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Opioids Much Underutilizedin Modern Psychiatry
Panksepp Bishop (1981).
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Depression-Pleasure Deficit.
Buprenorphine will Help!
Panksepp Bishop (1981).
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Buprenorphine Treatmentof Refractory Depression

• Opiates were used to treat depression until
  mid-1950s
• Subjects ten treatment refractory unipolar
  depressives
• Methods ten subjects started at .15 mg
  buprenorphine
• Seven completed 4-6 week trial three dropped out
  (nausea)
• Six of seven showed clinically striking
  improvments
• Four showed complete remission (HAM-Ds lt 6)

Bodkin, J.A., Zornberg, G.L, Lukas, S.E. Cole,
J.O. (1995). Buprenorphine treatment of
refractory depression, Journal of Clinical
Psychopharmacology, 15, 49-57
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Patient 1

• A 45-year-old, married, white academic physician
  with lifelong dysthymia, in psychotherapy since
  his late 20sfor the treatment of chronically
  depressed mood, low energy, social anxiety, and
  pervasive pessimism.
• Failed on phenelzine, bupropion, fluoxetine and
  amozapine some benefits from amitriptyline.
• Buprenorphine .15 mg thrice daily nasally to 0.9
  mg/day
• At this dosage, he felt he had not only
  recovered from depression but had achieved a new
  level of well-beingand hopefulness.
• HAM-D went from 30 to a score of 8 during 6 week
  trial.

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Patient 2

• A 41-year-old, married, male, high-level computer
  programmer with two young children. A very
  religious man. . . His first episode of
  depression was at age 15
• He had no sustained befits from desipramine,
  amoxapine, bupropion or fluoxetine.
• He felt better after first intranasal 0.15 mg of
  buprenorphine, and at the end of week his HAM-D
  had dropped from 21 to 4, and at the end of the
  week he reported himself to be 90 recovered. . .
  he was no longer lethargic. His demeanor was
  changed completely he conversed spontaneously,
  with a full range of affect. . . At the end of
  two weeks he felt completely recovered.

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Rat Laughter
Tickle Skin
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The Study of Positive Emotions

• Infant Humans
• Facial vocal displays(i.e. Duchenne smile)
• Approach behaviors

Adults Subjective self reports

• Other Animals
• Facial vocal displays
• Approach behaviors

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Play as an Index of Social Joy in Rats
Dorsal contacts

• All mammals tested engage in vigorous play
  behaviors during adolescence
• Rats find rough-and-tumble (RAT) play to be
  highly rewarding
• We monitor RAT play primarilyby counting dorsal
  contacts and pinning behaviors

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A Conceptual Framework for StudyingPlay in the
Rat
50 kHz USVs Rat Laughter?
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Function of PlayConstruction of the Social Brain

• Plato in the RepublicOur children from their
  earliest years must take part in the more lawful
  forms of play for if they are not surrounded by
  such an atmosphere they can never grow up to be
  well conducted and virtuous citizens.

Might PLAY Alleviate ADHD?
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Effects of Methylphenidate (MPH) on Play
(i.e. Ritalin)
Sensitization
Panksepp, J., Burgdorf, J., Gordon, N., Turner,
C. (2002). Treatment of ADHD with methylphenidate
may sensitize brain substrates of desire
Implications for changes in drug abuse potential
from an animal model. Consciousness Emotions,
3 7-19.
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If we want to sensitize anything,it would be
pro-social circuits of the brain.
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Frontal LobeExecutive Functions
Behavioral Inhibition
Behavioral Inhibition Being able to STOP, LOOK,
LISTEN,and FEEL
Executive Controls
1. Reflection Self-talk Self-questioning Understan
ding
2. Imagination Looking forwardand backwardwith
the minds eye(i.e. planning ahead)
3. Empathy Being able tothink about onesown
and othersfeelings
4. Creativity/Play Putting new ideasand goals
together Synthesis
Abilities
Consequences
Programmed by Life Experience
PLAY
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Brain GeneMicro-arrays(1,200 genes)
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Ultrasonic Calls Affective Self-Report
Rat Laughter
Positive Affect Sounds
Negative Affect Sounds
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50-kHz chirpsA rat model of positive emotion

• 50-kHz chirps are elicitedby a wide variety of
  rewards
• Aversive stimuli suppress 50-kHz chirps

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50-kHz chirpsA rat model of positive emotion

• 50-kHz chirps are elicitedby a wide variety of
  rewards
• Aversive stimuli suppress 50-kHz chirps

Animal Laughter?
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50-kHz chirpsA rat model of positive emotion

• 50-kHz chirps are elicitedby a wide variety of
  rewards
• Aversive stimuli suppress 50-kHz chirps

Beyond a Joke From Animal Laughter to Human
Joy. April 1, 2005 Science
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Discovery ChannelWhy Dogs Smile and Chimpanzees
Cry(Fleisher film, Inc.)
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Are 50-kHz calls of rats relatedto human
positive affect? 4 Hypotheses

• Negative affective stimuli should decrease
  50-kHz calls
• Positive affective stimuli should increase
  50-kHz calls
• Stimuli that elicit 50-kHz calls should be
  rewarding to rats
• Neural circuitry of 50-kHz calls should be
  similar to human Positive Affect

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ESB Induced 50-kHz calls
PFC
ms
BNST
DR
LPOA
Acc
VP
VTA
LH
Paxinos Watson (1998)
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Breeding for 50-kHz USVs
Happy Rats?
Sad Rats?
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Humans and other mammals sharethe same basic
emotional systems.
Questions?
Located in the most ancient regions of the brain.
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• Coming Up
• The Innovators lecture series

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It Takes a CommunityManaging In-home
Medicationsfor the Elderly
The InnovatorsMarch 7, Seattle

• Stephen Setter, Pharm.D., CGP, CDE
• Associate ProfessorDepartment of Pharmacotherapy
• College of Pharmacy

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Opening New DoorsCityLab Builds Math and
Science Literacy Among Underserved Children
The InnovatorsMarch 21, Spokane

• Sylvia Oliver, Ph.D.
• Assistant Director
• Health Research and Education Center,WSU Spokane

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Biological WarfareThe New Face of Terrorism
The InnovatorsApril 18, Seattle

• Thomas Preston, Ph.D.
• Associate ProfessorDepartment of Political
  Science
• College of Liberal Arts

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• For more information
• www.wsu.edu/theinnovators
• Toll free 1-877-978-3868

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http//www.juliusbergh.com/cocky/ 
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