1. Personality, Brain Function and Drug Effects on the Central Nervous System (CNS)
Craig strickland, ph.D., OWNER
BiobehaviorAL Consultation & Education

2. 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

3. Addictive personality disorder is not formally recognized as a personality disorder

4. 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

5. 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

6. 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!

7. 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

8. 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

9. 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

10. 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)

11. 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

12. 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

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

14. The Neurobiology of Addiction

15. The Reward System and Dopamine (DA)

16. Play Video here

17. 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

18. Neuroanatomy of Reward: The Rat

19. Neuroanatomy of Reward: The Human

20. Neuroanatomy of Reward: The Human
The Nucleus Accumbens

21. 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

22. 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

23. Neuroanatomy of Substance Abuse

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

25. 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

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

27. Neurobiology of Gambling

28. Play Video here

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

30. 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?

31. 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

32. 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

33. 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

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

35. 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…

36. 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!!!

37. Ventromedial Prefrontal Cortex (vmPFC)

38. 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

39. Inferior Parietal Lobule

40. 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)

41. 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

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

43. The Neurochemistry of Pathological Gambling

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

45. 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

46. 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

47. 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

48. 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

49. 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)

50. 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

51. 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

52. 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

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