Impaired Decision Making In Substance Use Disorders Claire Wilcox MD UNM Dept of Psychiatry Alcohol Medical Scholars Program © AMSP

Case 55 y.o. male Physician High intelligence Methamphetamine dependent Multiple prior treatments Negative consequences: unemployed Repeated relapses Wants to quit © AMSP

Decision Making Impairment Not question of self-control/intelligence Initial use of substances Escalation of problems Repeated relapses Decision making impairment → relapse Eg. of sugar for adaptive vs. maladaptive © AMSP

This Lecture Will Cover Neurocognitive aspects Neuroanatomical/neurochemical systems Malfunction in substance use disorder (SUD) Treatment implications © AMSP

How Are Decisions Made? Mental process Neurocognitive Involves 3 stages Interconnected Experience-driven © AMSP

Stage 1: Stimulus Assessment Preference Valence Salience Context © AMSP

Stage 2: Execution Stage 1: Assessment Action selection Action performance Action completion © AMSP

Stage 3: EFFECT!! Evaluation/feedback: pros and cons of choice © AMSP

Classical/ operant conditioning Stage 1: Assessment Stage 2: Execution Stage 3: Effect Stage 3: Learning Summarize again Classical/ operant conditioning © AMSP

Stage 1 Modifiers Assessment State (hunger, mood, intox, withdrawal) Psychological processes/traits “Impulsivity” Emotion regulation Attention (stimulus) Craving Cost-benefit analysis Assessment © AMSP

Stage 2 Modifiers Preference from stage 1 Moderating psychological processes/traits Flexibility Inhibitory control Selective attention Sustained attention Execution © AMSP

Stage 3 Modifiers Action from Stage 2 Experience of outcome Timing of effect Moderating psychological processes/traits Value/reward encoding Ability to process pros/cons Error calculation Learning Effect Learning © AMSP

Stages In Case Stage 1 Stage 2 Stage 3 Saw friend use Frustrated/stressed Stage 2 Became obsessed Unable to fight impulse Drug decreased anxiety/ neg affect when sees cue in future b/c happen later in time Stage 3 Use pleasure, relief  drug use reinforced © AMSP

Lecture Neurocognitive aspects Neuroanatomical/neurochemical systems Malfunction in substance use disorder (SUD) Treatment implications © AMSP 14

Dopamine Salience Cost benefit analysis Attention (stimulus) Stage 1:Assessment Attention (selective, sustained) Action selection, execution Stage 2:Execution ‘High’ Conditioned learning  Stage 3: Effect & Learning © AMSP

Noradrenaline Stress response Sympathetic NS(fight/flight) CRF release Stage 1:Assessment Optimizing performance/focus  exploration of options Stage 2:Execution Learning Conditioning Stage 3: Learning © AMSP

Glutamate Preference formation Cue-elicited behavior Action selection Stage 1:Assessment Action selection Stage 2:Execution Learning Conditioning Stage 3: Learning © AMSP

Prefrontal Cortex (PFC) Anterior Cingulate (ACC) Stage1: Assessment DS VS PFC/ACC Stage2: Execution Stage3: Effect Learning Dorsal Striatum (DS) Ventral Striatum (VS) Prefrontal Cortex (PFC) Anterior Cingulate (ACC) © AMSP 18

Brain areas activated by: Alcohol cues Cocaine cues © AMSP 20 19

Dopamine: From Ventral Tegmental Area (VTA) & Substantia Nigra (SN) PFC/ACC Dopamine: From Ventral Tegmental Area (VTA) & Substantia Nigra (SN) Striatum VTA/SN © AMSP

PFC/ACC Noradrenaline From Locus Coeruleus (LC) Amygdala LC © AMSP

Glutamate PFC/ACC Striatum Amygdala © AMSP

Lecture Neurocognitive aspects Neuroanatomical/neurochemical systems Malfunction in substance use disorder (SUD) Treatment implications © AMSP 23

Decision Making In SUDs Failure at any of 3 stages Biological root Possible pre-morbid deficits Worsened by drug use DA release to reward DA receptor density NA and CRF to stress © AMSP 24

Stage 1 Deficits  Response to cue Preference,short-term reward/”high” Stress,  cue salience © AMSP 25

Stage 2 Deficits Habitual actions favored Can’t see other options  Inhibitory control Can’t hold back © AMSP

Stage 3 Deficits Imbalanced reward encoding First drug use,  reward Once dependent  Drug reward Further drug consumption  Learning from negative © AMSP

Case Stage I:  preference for drug Stage II:  inhibitory control Stage III: / response to drug Stage III:  response neg consequence © AMSP

Lecture Neurocognitive aspects Neuroanatomical/neurochemical systems Malfunction in substance use disorder (SUD) Treatment implications © AMSP 29

Prevention  Exposure Target high-risk Adolescents Genetically vulnerable Cognitive probs (schizophrenia, brain injury)  Stress reactive (depressed/anxious) © AMSP

Treatment of SUD  Adaptive decision making  relapse Medications (target any of 3 stages) Psychotherapy Improve choices Avoid triggers © AMSP

Medications  Drug cue effect Naltrexone (AUDs), opioid blocker  DA release after ETOH  craving  relapse © AMSP

Medications  Negative emotional states drug craving Methadone (opioid use disorder)  Withdrawal/craving  brain stress response/  anxiety Treat co-occurring disorders © AMSP

Medications Cognitive functioninhibitory control Experimental Varenicline (nicotine use disorders) Memantine (Alzheimer’s Disease) © AMSP

Medications  Drug reward Under development Cocaine & nicotine vaccines Abs block drug entry into brain © AMSP

Psychotherapies Contingency Management Therapy Reward changes behaviors Learn abstinence  earn $$$ Relapse Prevention Therapy Identify triggers Learn avoidance © AMSP

This lecture covered Neurocognitive aspects of decision making Neuroanatomical/neurochemical systems How systems can malfunction in SUD Treatment implications © AMSP

Thanks to: Dr. Ann Manzardo (a power point genius) Dr. Marc Schuckit (for an excellent learning experience, and all of his help and time) Alcohol Medical Scholars Program (for the yummy food and spectacular hotels) © AMSP 38 38