Update University of North Carolina School of Medicine JarrettBarnhillmeduncedu History Psychiatry Neuropharmacologist or Alchemist We are but Dwarfs on the backs of giants Galileo BaconDescartesWilliam James ID: 600314
Download Presentation The PPT/PDF document "Behavioral Pharmacological" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Behavioral Pharmacological: Update
University of North Carolina School of Medicine
Jarrett_Barnhill@med.unc.eduSlide2
History: Psychiatry, Neuropharmacologist or Alchemist
We are but Dwarfs on the backs of giants
Galileo, Bacon/Descartes/William James
Instrumentality – what we know is useful because it predict what will happen.
Reason is bane of science; experiment is the key; Cogito ergo
est
Pragmatist
Anthropomorphizing/just the behavior, Ma’amSlide3
“Modern” ScienceEvidenced based medicine- the shoulders; Bacon is alive and well; Descartes is rolling over
Empiricism, categorical diagnosis, description psychiatry; leave etiology to the Shamans
Inductive-deductive reasoning: do the most recent findings explain the phenomenon
Pharmacogenomics; molecular genetics and neurobiology- newer is better, or is it? Slide4
This presentation is not for sissiesBehavioral models- can be autopsied and teach us new things
We are a generation of reductionists-
Programming- the concept of timing, critical periods and interactive specialization
Shiva and brain development- neurogenesis- apoptosis; LTP/LTD- synaptic pruning;
Glymphatics
, inflammatory
autophhagy
Slide5
Challenging BehaviorsDisruptive social , aggressive, self-injurious, and repetitive behaviors, fear-related behaviors
Functional behavioral analysis- ABCs, operationalized, quantitative and qualitative data
Boundary between behavioral excesses and deficiency states
Biopsychosocial, ethological factors Slide6
Challenging Behavior- Treatment Issues
Limited success finding drugs for specific behaviors
Most challenging behaviors are extremely heterogeneous conditions
Functional Behavioral Analysis is a critical step but more information is needed
Relationship between brain function, neurochemistry, and target behavior Slide7
Analysis of Functional Behavioral AnalysisFunction: approach-avoidance, intensity of drive, valence of reinforcement, arousal, positive negative affective state
Antecedents: assessment of stimulus/setting, pos/neg affective valence
Behaviors: careful subtyping
Consequences: ease of reinforcement; resistance to extinctionSlide8
Analysis of FunctionFunction of behavior- arousal, reactivity, motivational state, approach-avoidance, autonomic regulation
Drive or craving, reward potential, hedonic drive
Neuroticism- negative, emotional reactivity
Behavioral inhibition, conflict
Escape behaviors-sensitivity, threshold, anxiety tolerance, perception Slide9
Another Look at Antecedents and BehaviorAntecedents or trigger events, positive/negative experience, setting, memory, conditioning experiences, social factors
Classical conditioning (initiating)- CS/CR impact motivation (escape); intensity of reward potential (approach); Temperamental and presence of psychiatric disorders
Fear conditioning- LTP (panic disorder)Slide10
Other Factors Affecting Consequences
Ease of conditioning, extinction, reversal learning
Operant learning- valence of re-
inforcer
Extinction- LTD (long term depression)
Extinction spurt or increased appetitive behaviors
Multiple layers of conditioning- panic disorder with agoraphobia Slide11
Behavioral PsychopharmacologyMerges behavioral and pharmacological models
Neurobiology and neurochemistry of behavior and learning
Look at the plasticity and changes in gene expression due to “environmental” factors
Molecular genetics of some behavioral phenotypes Slide12
SIB: A Diverse Collection of BehaviorsTopography, typology, intensity, frequency, setting and trigger events
Functional Behavioral Analysis is a critical tool but has limits
Relationship to genetic disorders- specific topographies
Developmental models- do not always address special vulnerabilities Slide13
SIB: Behavioral Pharmacological Dissection
Why do some people develop progressive SIB when others in the same environment don’t?
Why does it persist in spite of pain, tissue destruction?
What initiates and maintains this particular typography?
What gets in the way of extinction- self-restraint? Slide14
Behavioral Pharmacology of Self-Injurious Behaviors
Complex relationship between SIB, behavioral phenotypes, and environment
Gene expression is continually influenced by environmental events and learning
Temperamental style influences helps shape life experiences and learning environment
Think in terms of an ecosystem Slide15
SummaryBehavioral pharmacology- neurobiological mechanisms associated with behavioral models- motivation, reinforcement, extinction
etc
Adds another layer of analysis to functional behavioral analytic data; makes things more complicated
D-
cycloserine
,
fenobam
, NAC, anti-inflammatory drugs - new age of ideas Slide16
How to Approach Treatment NonrespondersSlide17
Ideas on Drug ClassificationChallenging behavior- anti-aggressive drug
Syndrome specific- antidepressant or antipsychotic
Mechanism specific- serotonin re-uptake inh. or dopamine antagonist
Behavioral pharmacology- drug effects on learning and types of conditioningSlide18
Basics of psychopharmacologyDrug mechanisms- more complex than originally described
Pharmacokinetics- how do the drugs get there; genetic differences in rates
Pharmacodynamics- what the drugs do when they get there; genetics of receptor variability
Pharmaco-genomicsSlide19
Pharmacology of LearningMotivational states- reward potential (BFS), inhibition (BIS)
Linkage to VTA-n accumbens: reward pathways
Septo-hippocampal system, memory circuitry, LTP/LTD
MPF/orbital cortex- top down regulation
Attachment/social pathwaysSlide20
What exactly is a nonresponder?Wrong person, wrong diagnosis or learning model, wrong drug or intervention
Incomplete functional behavioral analysis
Incomplete understanding of the bio-behavioral issues
Drug issues- wrong dose; theory of drug effect and connection between it and behaviors is incomplete Slide21
TheoriesIntrinsic reinforcement- shift from positive to negative maintenance strategies; what happens to endorphins
Factors that trigger SIB- stress, urge to act, balance between aggression and SIB when restricted; craving and HPA axis
Problem with extinction- requires learning at a molecular biological level, LTD; Glutamate/NMDA activity; ACTH/AVPSlide22
Pharmacology of LearningMotivational states- reward potential (BFS), inhibition (BIS)
Reward pathways
Memory circuitry, LTP/LTD
Top down regulation- extinction
Attachment/social pathwaysSlide23
What Does All This Mean?We need to think beyond medications as syndrome or target behavior specific
We need to expand our concept of functional behavioral analysis to include neurobiological and molecular genetic input
We need to rethink our gene-environment; behavioral-psychiatric shibbolethsSlide24
Summary and ConclusionsDon’t abandon any models, combine them where you can, apply new syntheses to problem cases first. Research
Domain Criteria
Functional Behavioral Analysis- there is no black box, no black slate
Genetic disorders- genes are blueprints not the final product, think in transactional termsSlide25
Summary and Conclusions- cont’d Most psychopharmacological agents are not really syndrome specific- the brain is too complex
Theories of action change and are often either wrong or incomplete
Drugs can affect gene function, some are being applied to specific behavioral phenotypes Slide26
Summary and Conclusions- cont’d
Target symptoms, challenging behaviors and psychiatric disorders are final common pathways
We aren’t very good at treating core features, yet
Drugs effects on gene expression is a step beyond simple neurotransmitter modelsSlide27
How Do We Do This?Look at our existing tools of analysis- how can we adapt what we have
Keep up as best you can with the neurosciences of developmental and genetic disorders
Take a careful look at programs that don’t work, scatter plots, ethograms, and consider the neurobiology of function