Personality, Brain Function and Drug Effects on the Central Nervous System (CNS) Craig strickland, ph.D., OWNER BiobehaviorAL Consultation & Education HTTPS://SITES.GOOGLE.COM/SITE/BIOEDCON STRICKKAT@verizon.NET

Learning Objectives Describe the concept of “addictive personality” based on traits associated with current personality disorders Summarize the structural and chemical processes associated with addiction Using gambling addiction as a model, list several areas of the brain which might account for some behavioral traits associated with addiction

Addictive personality disorder is not formally recognized as a personality disorder

Addictive Personality: Is there such a thing? Criterion A: Elements of Personality Functioning (from emerging models DSM5, Section III) includes: Self: Identity: Experience of oneself as unique; clear boundaries between self and others; stability of self-esteem; accuracy of self-appraisal; capacity for and ability to regulate a range of emotional experience(s) Self-direction: Pursuit of coherent/meaningful short-term goals; use of constructive & prosocial internal standards of behavior; ability to self-reflect productively

Addictive Personality: Is there such a thing? Elements of Personality Functioning (from emerging models DSM5, Section III) includes: Interpersonal: Empathy: comprehension/appreciation of others’ ex-periences & motivations; tolerance of differing perspectives; understanding the effects of one’s behavior on others Intimacy: depth and duration of connection with others; desire and capacity for closeness; mutuality of regard reflected in interpersonal behavior

At this point, after reading the previous two slides, I am sure you have decided that we ALL have a personality disorder…but wait… Long standing Pervasive Patterned and repeated Lesson: Be careful when you read the DSM!

Addictive Personality: Is there such a thing? Criterion B: Five Pathological Personality Traits Negative Affectivity (vs. Emotional Stability) Emotional lability; Anxiousness; Separation insecurity; Submissiveness; Hostility; Perseveration Detachment (vs. Extraversion) Withdrawal, Intimacy avoidance, Anhedonia; Depressivity; Restricted Affectivity; Suspiciousness

Addictive Personality: Is there such a thing? Criterion B: Five Pathological Personality Traits Antagonism (vs. agreeableness): Manipulativeness; Deceitfulness; Grandiosity; Attention Seeking; Callousness; Hostility Disinhibition (vs. Conscientiousness): Irresponsibility; Impulsivity; Distractibility; Risk Taking; Rigid Perfectionism Psychoticism (vs. Lucidity): Unusual beliefs/Experiences; Eccentricity; Cognitive and Perceptual Dysregulation

Addictive Personality: Is there such a thing? Criterion C: Pervasiveness Criterion D: Stability Criteria E, F and G E: Impairments not better explained by another mental disorder F: Impairments not solely attributable to physiological effects of a substance or another medical condition e.g. head trauma G: Impairments not better understood as normal for an individual’s developmental stage or sociocultural environment

Addictive Personality Traits If we are talking about a true personality disorder, then the traits must be longstanding & pervasive So perhaps we need to look at what traits may have existed before the substance use began… Report prepared for the National Academy of Sciences: there is no single set of psychological characteristics that embrace all addictions but there may be some common elements across different addictions (next slide)

Traits Across Different Addictions Impulsivity Difficulty delaying gratification Antisocial Personality traits Disposition toward sensation seeking A high value on nonconformity combined with weak commitment to the goals for achievement valued by society Sense of social alienation; general tolerance for deviance Sense of heightened stress

Risk Factors Note: there is probably an interaction effect between traits and risk factors (as seen in other personality disorders) Lack of self-esteem Marked depression or anxiety Physical/sexual abuse or other traumatic exposure in especially in childhood (Adverse Childhood Events {ACE} study) Sharply conflicting parental expectations Biology

What causes Behavioral Health Disorders? The Diathesis Stress Model Environmental Risk Factors AND/OR Genetic vulnerability: Neurobiology Personality Traits

The Neurobiology of Addiction

The Reward System and Dopamine (DA)

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The Brain & Reward 1954: James Olds was trying to stimulate the reticular formation Electrode ended up in another part of the brain Animals would press a lever to receive stimulation Press 700 times or more per hour A very potent reinforcer

Neuroanatomy of Reward: The Rat

Neuroanatomy of Reward: The Human

Neuroanatomy of Reward: The Human The Nucleus Accumbens

Evidence for Dopamine & Reward Addictions & CNS: Tx Trends 11_5_10 Evidence for Dopamine & Reward Electrical stimulation of the Nucleus Accumbens is reinforcing Animals will press lever for substances which enhance DA release which includes most drugs of abuse Non-drug reinforcers e.g. Sex, water, food, gambling, etc. produce release of DA in the N. Accumbens

Evidence for Dopamine & Reward Addictions & CNS: Tx Trends 11_5_10 Evidence for Dopamine & Reward Psychostimulants: Cocaine: blocks re-uptake (increases available DA) Amphetamines: blocks re-uptake & stimulates DA release Medications/Drugs which block DA release reduce the ability to experience pleasure Craig’s Research on the Reward System

Neuroanatomy of Substance Abuse

Neural Communication: Iontotropic Addictions & CNS: Tx Trends 11_5_10 Neural Communication: Iontotropic 24

So addictive tendencies (traits) could arise from: Underactive reward system (cellular level) Not enough dopamine being produced in the brain Increased sensitivity to drugs of abuse Could lead to faster development of tolerance which would lead to quicker development of withdrawal Higher than normal amounts of the enzyme which degrade dopamine Monoamine oxidase (MAO) Catechol-O-methyltransferase (COMT) Enhanced liver enzyme activity Enhanced dopamine reuptake processes

Let’s apply some of this neurobiology to a specific addiction

Neurobiology of Gambling

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Pathological Gambling (PG): A Compulsive Disorder or an Addiction?

Diagnostic and Statistical Manual (DSM) of MH Disorders: PG Classification Pathological Gambling (PG) first recognized by the DSM in 1980 Historically, PG: considered an “impulse control disorder” rather than a behavioral addiction Thus, PG was included in impulse control disorders along with pyromania, kleptomania, trichotillomania and intermittent explosive disorder (IED) DSM-5 considers PG to be an addiction. Is there a role for impulsivity (trait) within PG diagnosed as a behavioral addiction?

The Case for PG as an Addiction Drug dependence and PG share several characteristics Continued engagement in the behavior despite negative consequences Diminished self-control over the behavior Compulsive engagement in the behavior An appetitive urge or craving state prior to engagement in the behavior

The Case for PG as an Addiction Drug dependence and PG share several characteristics (cont.) Tolerance and withdrawal Repeated unsuccessful attempts to cut back or quit Interference with major areas of life functioning

Overview of Critical Brain Areas Researched in Addiction and PG The Brain’s Reward System Frontal Cortex Ventral portion Dorsal portion Prefrontal Cortex Cingulate Cortex Dorsal Anterior portion Ventral Anterior portion Other

The Brain’s Reward System (ventral striatum) Ventral Tegmental Area (VTA) Nucleus Accumbens Prefrontal Cortex Amygdala & Other Limbic System Structures

Reward System Research (Potenza, M. 2008) Those with Pathological Gambling (PG) showed decreased activity in the brain’s reward system (ventral striatum) when viewing videos of gambling activities Similar result when subjects are those with drug addictions viewing videos of addictive activities Points to hypoactivation as common to both conditions… Hypoactivation….hmmm…

Reward System Research (Potenza, M. 2008) Again, those with PG showed decreased activity in the brain’s reward system (ventral striatum) when viewing videos of gambling activities But why hypoactivation versus hyper-activation? Is hypoactivation a cause of or a result from addiction? Note: control subjects showed increased activation Tolerance!!!

Ventromedial Prefrontal Cortex (vmPFC)

Ventromedial Prefrontal Cortex (vmPFC) Decrease in brain activity in this and other prefrontal cortical areas in PG and addiction Controls showed increased activity PGs show decrease in activity related to decrease in ability to process monetary gains and losses (e.g. behaviors are “riskier”) Another way of saying this, decreased ability to relate behavior & consequence

Inferior Parietal Lobule

Inferior Parietal Lobule (Potenza, 2008) Brain region implicated in the response inhibition component of impulse regulation Compared to controls, there was less activity in this region for both PG and drug-dependent study subjects Not certain whether this impulse dysregulation due to inappropriate use of cues/stimuli (sensory) or behavioral (movement)

Summary Decrease in ventral striatum (reward) system activity Decrease in ventro-medial prefrontal cortex activity Decrease in parietal lobe activity Cause of PG? or tolerance? Changes in behavior-reinforcement relationship Decrease in impulse regulation/response inhibition

Example of the Biology of Traits Phineas Gage (1848):

The Neurochemistry of Pathological Gambling

The Chemicals in Question Norepinephrine/epinephrine (NE/E also known as noradrenaline/adrenaline) Serotonin (5-HT or 5-hydroxytryptamine) Dopamine (DA) The Opioids Glutamate

Norepinephrine/Epinephrine (NE/E) Associated with the autonomic nervous system (fight or flight response and general arousal) Gambling & associated behaviors associated with autonomic arousal Men with PG show higher NE/E levels compared with controls

Norepinephrine/Epinephrine (NE/E) Medications which block/reduce NE/E levels could have therapeutic effects Clonidine, guanfacine, Inderal, Tenex Interestingly, these meds. used to treat ADHD and perhaps other impulsive disorders In the elderly, need to be cautious given the effects of these medications on lowering blood pressure

Serotonin (5-HT) Low serotonin levels have been associated with impulsivity, depression, anxiety, etc. Those with PG or impulsive aggression show low levels of 5-hydroxy indoleacetic acid (5-HIAA), a serotonin metabolite

Serotonin (5-HT) Data is somewhat mixed but promising SSRIs (Prozac, Paxil, Zoloft, etc.) Data is somewhat mixed but promising SSRIs may also help with co-occurring anxiety disorders, depression, etc. As a function of aging, density of serotonin receptors decreases in the CNS Thus, these medications could be particularly beneficial for an older population

Dopamine (DA) DA strongly associated with reward, reinforcing behaviors and addiction; however DA modulating medications have not been studied in PG Using DA agonists for people with Parkinson’s Disease (PD) can initiate impulse control dysfunction including that seen in PG Effect also seen when these drugs are used with people suffering from restless leg syndrome (RLS)

Dopamine (DA) In study of subjects with RLS without PG Dopamine agonists increased activity in the brain’s reward system (ventral striatum) Note: time course re: ventral striatum activity

Dopamine (DA) Hypersexuality Compulsive shopping & eating Other behaviors in addition to PG noted as a result of DA agonist use: Hypersexuality Compulsive shopping & eating Punding (compulsive fascination with and performance of repetitive, mechanical tasks) What is needed are studies where DA modulating meds. are directly with those with PG

Opioids Opioids implicated in pleasure and reward Opioids influence activity in the ventral striatum Given this, opioid antagonists were investigated Naltrexone superior to placebo in reducing gambling associated behaviors (some issues with liver functioning however) Nalmefene: also superior to placebo, no liver function issues A family history of alcoholism was strongly associated with a positive drug response

That’s my story and I am stickin’ to it!