By:

Brian Zachariah M.D. PGY4

Lauren Derhodge D.O. Clinical Assistant Professor, Attending Physician

LEARNING OBJECTIVES

• DEFINE IMPULSIVITY

• BRIEFLY REVIEW NEUROBIOLOGY AND NEUROPATHOLOGY ASSOCIATED WITH IMPULSIVE

BEHAVIOR IN RELATION TO ADDICTION

• EXPLORE ASSOCIATION BETWEEN SUBSTANCE USE DISORDERS (SUD’S) AND IMPULSIVITY THRU

PERSONALITY INVENTORY DATA AS IT RELATES TO FOUR CLASSES OF SUBSTANCES

(STIMULANTS, ALCOHOL, OPIATES, MDMA)

• UNDERSTAND THAT IMPULSIVITY SERVES AS A PRE-EXISTING ADDICTION VULNERABILITY

MARKER BY REVIEWING:

• STUDIES OF GROUPS AT HIGH-RISK FOR DEVELOPMENT OF SUDS

• STUDIES OF PATHOLOGICAL GAMBLERS

• GENETIC ASSOCIATION STUDIES LINKING IMPULSIVITY TO GENETIC RISK FACTORS FOR ADDICTION

• BRIEFLY DIFFERENTIATE BETWEEN THE AVAILABLE CLASSES OF AGENTS AND RECOGNIZE HOW

EFFECTIVE THEY ARE FOR SPECIFIC IMPULSIVE BEHAVIORS

RELEVANCE?

• BIOLOGICAL MECHANISMS OF ADDICTION HAVE BEEN EXPLORED IN GREAT DETAIL,

UNCOVERING NEUROBIOLOGY OF DRUG USE AND EFFECTS OF CHRONIC DRUG EXPOSURE.

• HOWEVER,

• COGNITIVE ASPECTS OF ADDICTION REMAIN RELATIVELY UNEXPLORED DESPITE EVIDENCE THAT

DISRUPTION OF COGNITIVE CONTROL IS A HALLMARK OF ADDICTION

• SEVERAL STUDIES DEMONSTRATE THE IMPORTANCE OF PRE-MORBID CHARACTERISTICS IN THE

DEVELOPMENT OF LATER ADDICTION BUT THEY MAINLY HIGHLIGHT THE ROLE OF REWARD

PROCESSES, RATHER THAN PRE-MORBID IMPULSIVITY AND INHIBITORY CONTROL, AS CRITICAL

IN THE DEVELOPMENT OF SUDS

Everitt et al., 2007; Jentsch and Taylor, 1999; Robinson and Berridge, 2003

IMPULSIVITY AS A PSYCHOLOGICAL CONSTRUCT• IMPULSIVITY HAS A RANGE OF DEFINITIONS

• ACTIONS THAT ARE POORLY CONCEIVED,

• PREMATURELY EXPRESSED,

• UNDULY RISKY OR INAPPROPRIATE TO THE SITUATION THAT OFTEN RESULT IN UNDESIRABLE

CONSEQUENCES

Evenden, 1999b, de Wit, 2009

• COMPONENTS OF IMPULSIVITY INCLUDE

• ATTENTION,

• SUPPRESSING RESPONSES,

• POOR EVALUATION OF CONSEQUENCES AND/OR AN INABILITY TO FORGO IMMEDIATE SMALL REWARDS IN FAVOR OF GREATER DELAYED REWARDS.

IMPULSIVITY WITHIN EXECUTIVE FUNCTION

• AT TIMES, IMPULSIVITY IN PERSONALITY IS VALUABLE FOR RAPID DECISIONS

AT OPPORTUNE TIMES.

• EXECUTIVE FUNCTIONS IN COGNITIVE PSYCHOLOGY CONTROL ABSTRACT

THINKING, RULE ACQUISITION, PLANNING AND FLEXIBILITY IN RESPONSES

INCLUDING RULE SHIFTING, AS WELL AS INITIATING APPROPRIATE ACTIONS

AND INHIBITING INAPPROPRIATE ACTIONS.

• WITH REPETITION, DECISIONS REQUIRE LESS ATTENTION AND MAY BE RAPID,

LEARNED, BUT ARE NOT NECESSARILY IMPULSIVE.

• IMPULSIVITY LEADS TO RAPID RESPONSES WITHOUT REFLECTION.

IMPLICATED NEUROBIOLOGY AND NEUROPATHOLOGY

• THE FRONTAL LOBES ARE COMMONLY DIVIDED

INTO FIVE PARALLEL, THOUGH INTERACTING,

SUBCIRCUITS: MOTOR, OCULOMOTOR,

DORSOLATERAL, ORBITOFRONTAL CORTEX (OFC),

AND ANTERIOR CINGULATE.

• THE DORSOLATERAL PREFRONTAL CIRCUIT (DLPFC)

UNDERLIES EXECUTIVE FUNCTION, WHICH

INCLUDES THE CONTROL OF ATTENTION, AS WELL

AS THE SUSTAINED ORGANIZATION OF BEHAVIOR

TO SOLVE COMPLEX PROBLEMS

• THE DLPFC IS ESSENTIAL TO DRAW ATTENTION TO

IMPORTANT FACTORS AND TO ACTIVELY SELECT

GOALS.

Alexander et al., 1986; Cummings, 1993; Stuss and Alexander, 2000; Abe and Hanakawa, 2009; Bonelli and Cummings, 2007; Carmichael and Price, 1995a,b

The dlPFC and OFC is associated with behavioral regulation

owing to its unique capacity to maintain and integrate sensory,

affective, and associative information.

The medial prefrontal/cingulate

circuit is critical for feedback

monitoring and motivation, with

lesions producing profound

apathy.

• EXECUTIVE FUNCTIONS ARE OFTEN INVOKED

TO OVERRIDE RESPONSES THAT HAVE BEEN

AUTOMATICALLY ELICITED.

• THE FRONTAL LOBE EXECUTIVE FUNCTIONS

RECEIVE INPUT FROM ALL SENSORY

MODALITIES, INTEGRATE MEMORIES AND

USING WORKING MEMORY OF TEMPORARY

INFORMATION, ASSEMBLE REWARD AND

VALUATION INFORMATION WITH TIMING OF

EVENTS TO CARRY OUT PLANNED BEHAVIORS.

THE AMYGDALA'S (AMG) ABILITY TO DRIVE IMPULSIVE,

NON-REFLECTIVE RESPONSE SELECTION (OR DECISION-

MAKING) STEMS FROM IT’S KEY ROLE IN CONDITIONED

RESPONDING, WHEREBY APPETITIVE OR AVERSIVE STIMULI

(OR CONTEXTS) COME TO TRIGGER AUTOMATIC

RESPONDING TO THOSE STIMULI.

Balleine and Killcross, 2006

The product of such conditioning in the amygdala (AMG) is

thought to underlie the craving triggered by people, places, and

things associated with drug use.

• EXECUTIVE FUNCTION CAN BE ALTERED BY ENVIRONMENTAL FACTORS THAT CHANGE DIRECTED

GOALS.

• FOR EXAMPLE, SMELLING POPCORN WILL DISTRACT INDIVIDUALS, DRAW THEM TO THE SOURCE, INDUCE

HUNGER AND AUTOMATICALLY STIMULATE EATING.

• THIS IS NORMAL; HOWEVER, NOT ALL WILL BE DISTRACTED.

• PEOPLE, WHO ARE DIETING, ACTIVATE EXECUTIVE FUNCTIONS DRAWING ATTENTION TO THE

DISTRACTING SMELL AND BLOCK EATING, OFTEN THROUGH A STRATEGY OF LEAVING THE AREA AND

AVOIDING FURTHER DISTRACTION.

• IMPULSIVITY CAN INCLUDE WEAK INHIBITORY CONTROL, LACK OF ATTENTION, OR BAD DECISIONS.

• THUS, EXECUTIVE FUNCTIONS OPPOSE IMPULSIVITY.

• SIMILAR FACTORS MAY BE INVOLVED IN SUBSTANCE CRAVING CUES PROMOTING USE AND/OR

CAUSING RELAPSE.

• AMYGDALA ACTIVATION HAS BEEN SUGGESTED TO CAUSE THE

NEGATIVE MOTIVATIONAL STATE THAT DRIVES ADDICTION

• SUPPORTED BY HUMAN NEUROIMAGING DATA SHOWING

AMYGDALA HYPERACTIVATION IN RESPONSE TO STIMULI THAT

INDUCE CRAVING.

• THUS, A WEAKNESS IN EXECUTIVE FUNCTION TIPS THE

DECISIONAL BALANCE FROM DLPFC-OFC-ACC CONTROLLED

RESPONSES, PARTICULARLY IF AMG TO DRIVE CREATES URGENCY

THAT PROMOTES IMPULSIVE, AUTOMATIC RESPONDING TO

DOMINATE BEHAVIOR

Koob, 2009; Breiter et al., 1997; Childress et al., 1999; Kilts et al., 2001;

IMPULSIVITY – STIMULANT (COCAINE/METHAMPHETAMINE) USE DISORDER

• ELEVATED IMPULSIVITY SCORES ON SELF-REPORT MEASURES (TYPICALLY THE BIS) HAVE BEEN

DEMONSTRATED IN COCAINE-DEPENDENT OUTPATIENTS AND YOUNG STIMULANT USERS

• ELEVATED BIS SCORES WERE CORRELATED NEGATIVELY WITH AGE OF FIRST COCAINE USE,

CONSISTENT WITH A VULNERABILITY PATHWAY WHERE HIGH IMPULSIVITY PREDISPOSE EARLY

RECREATIONAL DRUG-TAKING.

Coffeet al., 2003; Moeller et al., 2004; Leland and Paulus, 2005; Moeller et al., 2002

IMPULSIVITY – OPIATE (HEROIN) USE DISORDER

• ON SELF-REPORT MEASURES, HEROIN USERS HAVE SHOWN INCREASED IMPULSIVITY SCORES

ON THE BIS AND EYSENCK SCALE.

• HEROIN USERS ALSO SCORE LOWER ON PERSONALITY MEASURES OF FUTURE TIME

PERSPECTIVE, SUGGESTING DECREASED ABILITY TO PLAN AHEAD OR A HIGHER FOCUS ON

IMMEDIATE AS COMPARED TO DELAYED EVENTS .

Ersche et al., 2006; Verdejo-Garcia and Perez-Garcia, 2007; Kirby et al., 1999; Madden et al., 1997; Petry et al., 1998

IMPULSIVITY – ALCOHOL USE DISORDER

• ALCOHOL USE IS CONSISTENTLY ASSOCIATED WITH ELEVATED TRAIT IMPULSIVITY.

• RECENT STUDIES HAVE REPORTED THAT ALCOHOL DEPENDENT SUBJECTS HAVE HIGHER SCORES

ON THE UPPS SUBSCALE OF URGENCY, I.E. THE TENDENCY TO ACT IMPULSIVELY IN RESPONSE

TO NEGATIVE EVENTS, SENSATION SEEKING, AND MORE TRADITIONAL MEASURES SUCH AS

THE BIS.

Whiteside and Lynam, 2003; Bjork et al., 2004a; Mitchell et al., 2005

IMPULSIVITY – MDMA “ECSTASY” USE DISORDER

• MULTIPLE STUDIES HAVE SHOWN INCREASED TRAIT IMPULSIVITY IN ECSTASY USERS AS

MEASURED BY SEVERAL SELF-REPORT INVENTORIES.

• IN THESE STUDIES, BOTH RECREATIONAL AND HEAVY USERS SHOWED HIGHER SCORES ON

IMPULSIVENESS, VENTURESOME DESIRE AND SENSATION SEEKING.

Butler and Montgomery, 2004; Morgan, 1998; Parrott et al., 2000

IMPULSIVITY=PREEXISTING?

• THERE IS NO CONSISTENT ASSOCIATION BETWEEN THE DURATION OF DRUG USE AND

IMPULSIVITY, AND STUDIES OF ABSTINENT DRUG USERS TYPICALLY DETECT COMPARABLE

EFFECTS TO CURRENT USERS, AND MINIMAL CORRELATIONS BETWEEN IMPULSIVITY AND THE

DURATION OF ABSTINENCE.

• THIS IS CONSISTENT WITH THE HYPOTHESIS THAT IMPULSIVITY IS A PRE-EXISTING

CHARACTERISTIC IN DRUG USERS, WHICH DOES NOT CHANGE RADICALLY WITH THE

DEVELOPMENT OF THE ADDICTION OR WITH LONG-TERM ABSTINENCE.

IMPULSIVITY - ADOLESCENCE• ADOLESCENCE IS A CRITICAL PERIOD FOR THE DEVELOPMENT OF SUDS.

• RETROSPECTIVE STUDIES IN ADULT SUD GROUPS REPORT THAT THE INITIATION OF USE OF THE

SUBSTANCE OF LATER DEPENDENCE INVARIABLY STARTS BEFORE AGE 18.

• NEURODEVELOPMENTAL TRAJECTORIES DURING THE ADOLESCENT PERIOD MAY CONVEY

VULNERABILITY TO HIGH-RISK BEHAVIORS LIKE DRUG-TAKING, DUE TO

• RELATIVE IMMATURITY OF FRONTAL CORTICAL CONTROL SYSTEMS

• RELATIVE MATURITY OF STRIATAL SYSTEMS RESPONSIBLE FOR REWARD PROCESSING AND

MOTIVATION

• THIS IMBALANCE MAKES ADOLESCENCE A PERIOD DURING WHICH THE ACTIVITY OF THE

REWARD SYSTEM PREVAILS OVER THAT OF THE SYSTEMS GOVERNING AVOIDANCE OR SELF-

CONTROL.

(Helzer et al., 1991; Wagner and Anthony, 2002; Chambers et al., 2003; Ernst et al., 2006a

• CROSS-SECTIONAL STUDIES IN ADOLESCENT SAMPLES HAVE SHOWN THAT ELEVATED TRAIT

IMPULSIVITY (E.G. SENSATION SEEKING) AND HIGHER RATES OF DELAY-DISCOUNTING WERE

ASSOCIATED WITH EARLIER AGE OF ALCOHOL AND DRUG EXPERIMENTATION.

Kollins, 2003; Martin et al., 2002, 2004

• WONG ET AL. (2006) ASSESSED A SAMPLE OF 514 CHILDREN OF ALCOHOLICS AND MATCHED

CONTROLS TO ANALYZE THE IMPACT OF NEURODEVELOPMENTAL PATTERNS OF IMPULSIVITY

(AS MEASURED BY CLINICIANS’ RATINGS OF BEHAVIORAL SELF-CONTROL) AND RESILIENCY ON

SUBSEQUENT EXPERIMENTATION WITH DRUG USE AND SUD.

• IMPULSIVITY AND RESILIENCY WERE ASSESSED AT 3 YEARS INTERVALS USING FIVE WAVES OF

CHILDREN FROM 2- TO 14-YEAR OLD. THEIR RESULTS ELEGANTLY SHOW THAT SLOWER RATES

OF DEVELOPMENT OF BEHAVIORAL SELF-CONTROL STRONGLY AND SPECIFICALLY PREDICT

EARLY INITIATION OF DRUG USE AT AGE 14 AND HIGHER NUMBER OF DRUG-RELATED

PROBLEMS AT AGE 17.

IMPULSIVITY - ADHD AND EXTERNALIZING BEHAVIORAL PROBLEM ADOLESCENTS

• THERE IS A HIGHER PREVALENCE OF SUDS IN ADOLESCENTS AND ADULTS WHO WERE

PREVIOUSLY DIAGNOSED WITH ADHD AND OTHER EXTERNALIZING BEHAVIORAL PROBLEMS

DURING THEIR CHILDHOOD.

• ERNST ET AL., (2006A) CONDUCTED A PROSPECTIVE STUDY EXAMINING BEHAVIORAL

PREDICTORS OF DRUG-TAKING IN ADOLESCENTS WITH (N = 50) AND WITHOUT (N =28)

ADHD DIAGNOSES AGED 12–14, THE PARTICIPANTS COMPLETED THE BIS AND AN

AGGRESSION RATING SCALE, AND AT 4-YEAR FOLLOW-UP WERE SCREENED FOR THE

INITIATION OF SUBSTANCE USE.

• IN THIS STUDY, ADHD DIAGNOSIS DID NOT SIGNIFICANTLY PREDICT LATER USE OF ALCOHOL,

TOBACCO OR MARIJUANA BUT ELEVATED BIS IMPULSIVITY WAS A SIGNIFICANT PREDICTOR OF

ALCOHOL USE, AND AGGRESSION RATINGS WERE ASSOCIATED WITH TOBACCO AND MARIJUANA

USE.

Biederman et al., 1997; Molina et al., 2007; Wilens et al., 1997

• ELKINS ET AL. (2007) ASSESSED A LARGE SAMPLE OF 11-YEAR-OLD TWINS (760 FEMALE AND

752 MALE TWINS) FOR CATEGORICAL ADHD DIAGNOSIS, AS WELL AS DIMENSIONAL

MEASURES OF INATTENTION VS. IMPULSIVE/HYPERACTIVE SYMPTOMS. THEY USED THESE

ASSESSMENTS TO PROSPECTIVELY PREDICT DRUG USE INITIATION AND SUD.

• FOLLOW-UP ASSESSMENT OF OUTCOME VARIABLES AT AGES 14 AND 18 SHOWED THAT

DIMENSIONAL SYMPTOMS OF IMPULSIVITY/HYPERACTIVITY WERE STRONGER PREDICTORS THAN

INATTENTION OR ADHD DIAGNOSIS FOR INITIATION OF TOBACCO, ALCOHOL AND ILLICIT DRUGS

USE AT 14.

IMPULSIVITY IN ADOLESCENT OFFSPRING OF SUD PARENTS

• MORE CONSISTENT EVIDENCE IN FAVOR OF IMPULSIVITY AS A VULNERABILITY MARKER FOR

SUD COMES FROM CROSS-SECTIONAL AND LONGITUDINAL STUDIES OF CHILDREN WITH SUD

PARENTS.

• THESE STUDIES HAVE ELEGANTLY DEMONSTRATED THAT

• CHILDREN OF SUD PARENTS HAVE ELEVATED IMPULSIVITY BEFORE DRUG EXPOSURE AND

• IMPULSIVITY INDICES ARE STRONG RELIABLE PREDICTORS OF LATER DRUG INITIATION AND

DRUG/ALCOHOL PROBLEMS.

IMPULSIVITY – PROBLEM GAMBLER’S (PG’S)

• RATIONALE FOR STUDYING PG’S INCLUDE THAT VULNERABILITY MECHANISMS OVERLAP WITH

THAT OF THOSE WITH SUD’S BUT WITHOUT EXOGENOUS SUBSTANCE USE.

• CASE-CONTROL STUDIES COMPARING SELF-REPORTED IMPULSIVITY IN PG AND NON-GAMBLING

CONTROLS HAVE DEMONSTRATED ELEVATED SCORES ON THE BIS, THE EYSENCK IMPULSIVITY

QUESTIONNAIRE, THE CALIFORNIA PERSONALITY INVENTORY, EGO CONTROL SCALE, AND THE

ZUCKERMAN SSS.

• DEFICIENT PERFORMANCE ON NEUROCOGNITIVE MEASURES OF INHIBITORY CONTROL,

INCLUDING TESTS OF RESPONSE INHIBITION, DELAY-DISCOUNTING AND RISKY DECISION-

MAKING CAN BE NOTED AS WELL

Carlton and Manowitz, 1994; Fuentes et al., 2006; Petry, 2001c; Rodriguez-Jimenez et al., 2006a, Blaszczynski et al., 1997, McCormick et al., 1987, Potenza et al., 2003

GENETIC ASSOCIATION STUDIES OF IMPULSIVITY WITH RISK FACTORS FOR ADDICTION

PRACTICAL IMPLICATION?

• PERSISTENCE OF DEPENDENCE AND MOTIVATION TO CONTROL ADDICTIVE BEHAVIOR RELY ON

THE DECISIONAL BALANCE BETWEEN REFLECTIVE AND IMPULSIVE SYSTEMS

• neurobiology of

behavioral change

needed in recovery

from addiction requires

frontal-cortical

involvement

Hettema et al., 2005; Clay et al., 2008

• motivation interview

therapy and cognitive

behavioral therapy

activate frontal-cortical

executive functions that

through use promotes

maintenance of controlled

behavior.

• This activation of executive

functions increases

attention and frontal lobe

function reducing

impulsivity and preventing

relapse

SSRI’S:

• LOW LEVELS OF THE SEROTONIN METABOLITE 5-HYDROXYINDOLEACETIC ACID AND

BLUNTED SEROTONERGIC RESPONSE WITHIN THE VENTROMEDIAL PREFRONTAL CORTEX

ARE ASSOCIATED WITH IMPULSIVE BEHAVIORS, ESPECIALLY AGGRESSION.

• MOST BENEFIT NOTED IN PERSON’S WITH DEPRESSION OR ANXIETY WITH IMPULSIVE

BEHAVIORS AS A MEANS OF COPING

Coccaro EF, Lee RJ, Kavoussi RJ. A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J Clin Psychiatry. 2009;70:653-662.

PSYCHOPHARMACOLOGICAL OPTIONS FOR IMPULSIVITY

SNRI’S

• ANIMAL RESEARCH SUPPORTS AN EMERGING ROLE FOR THE NORADRENALINE SYSTEM IN

IMPULSE CONTROL

• NO PLACEBO-CONTROLLED TRIALS OF A NORADRENERGIC AGENT IN THE TREATMENT OF

MOST IMPULSE CONTROL DISORDERS

• ONE STUDY WITH ATOMOXETINE AND BINGE EATNG DISORDER

McElroy SL, Guerdjikova A, Kotwal R, et al. Atomoxetine in the treatment of binge-eating disorder: a randomized placebo-

controlled trial. J Clin Psychiatry. 2007;68:390-398.

• OPIOID ANTAGONISTS

• NALTREXONE PHARMACOTHERAPY FOR ALCOHOL DEPENDENCE INCREASES OFC ACTIVATION AND

APPEARS PROMISING FOR CERTAIN TYPES OF IMPULSIVE BEHAVIOR

• MOST NOTABLY ALCOHOL USE DISORDERS, GAMBLING DISORDER, AND KLEPTOMANIA

• GLUTAMERGIC AGENTS

• IMPROVING GLUTAMATERGIC TONE IN THE NUCLEUS ACCUMBENS HAS BEEN IMPLICATED IN

REDUCING THE REWARD-SEEKING BEHAVIOR IN SUBSTANCE ADDICTIONS

• THESE AGENTS MAY IMPROVE IMPULSIVITY BY DECREASING DRIVE

• N-ACETYLCYSTEINE (AVAILABLE OVER-THE-COUNTER), HAS SHOWN SOME BENEFIT IN TREATING

MARIJUANA DEPENDENCE, GAMBLING DISORDER, AND TRICHOTILLOMANIA

• MEMANTINE, AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, HAS SHOWN EARLY PROMISE IN

TREATING ALCOHOL USE DISORDERS, GAMBLING DISORDER, KLEPTOMANIA, AND COMPULSIVE

BUYING

Boettiger et al., 2009

Deepmala, Slattery J, Kumar N, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic

review. Neurosci Biobehav Rev. 2015;55:294-321.

Grant JE, Schreiber LR, Odlaug BL. Phenomenology and treatment of behavioural addictions. Can J Psychiatry. 2013;58:252-

259.

• ATYPICALS HAVE MIXED REPORTS

• OLANZAPINE – TRICHOTILLOMANIA BUT NOT

IN GAMBLING DISORDER

• RISPERIDONE AND QUETIAPINE IN CONDUCT

DISORDER

. Van Ameringen M, Mancini C, Patterson B, et al. A randomized, double-blind, placebo-controlled trial of olanzapine in the

treatment of trichotillomania. J Clin Psychiatry. 2010;71:1336-1343.

Grant JE, Leppink EW. Choosing a treatment for disruptive, impulse-control, and conduct disorders. Curr Psychiatry.

2015;14:29-

• LITHIUM

• MOST STUDIES ON BIPOLAR

MANIA AND EFFICACY IN

REDUCING IMPULSIVITY

ASSOCIATED WITH GRANDIOSITY

• 7 STUDIES DEMONSTRATING

EFFICACY IN ADOLESCENTS WITH

CONDUCT DISORDER

FUTURE CLINICAL IMPLICATIONS?

• CHARACTERIZATION OF VULNERABILITY MARKERS FOR ADDICTION IS ESSENTIAL FOR

• DETECTING AT-RISK INDIVIDUALS

• IMPLEMENT EARLY DETECTION AND TREATMENT INTERVENTION, THEREBY AVERTING THE DEVASTATING

EFFECTS OF LONG-TERM USE.

• STANDARDIZING PREDICTIVE CONSTRUCTS WHICH HIGHLIGHTS SPECIFIC RISK CATEGORIES

THAT MAY BE THE BASIS FOR SUD TREATMENT RECOMMENDATIONS

• TREATMENT IMPLICATIONS FOR COMORBID CONDITIONS WITH IMPULSE DISORDER AND SUD

REFERENCES

• FULTON TIMM CREWS, CHARLOTTE ANN BOETTIGER, IMPULSIVITY, FRONTAL LOBES AND RISK

FOR ADDICTION, PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR – ELSEVIER; SEPTEMBER

2009

• ANTONIO VERDEJO-GARCIA, ANDREW J. LAWRENCE, LUKE CLARK, IMPULSIVITY AS A

VULNERABILITY MARKER FOR SUBSTANCE-USE DISORDERS: REVIEW OF FINDINGS FROM HIGH-

RISK RESEARCH, PROBLEM GAMBLERS AND GENETIC ASSOCIATION STUDIES; NEUROSCIENCE

AND BIOBEHAVIORAL REVIEWS 32 (2008) 777–810, NOVEMBER 2007

• JON E. GRANT, JD, MD, MPH AND SAMUEL R. CHAMBERLAIN, MD, PHD,

PSYCHOPHARMACOLOGICAL OPTIONS FOR TREATING IMPULSIVITY, PSYCHIATRIC TIMES

• BLANCO C, POTENZA MN, KIM SW, ET AL. A PILOT STUDY OF IMPULSIVITY AND COMPULSIVITY

IN PATHOLOGICAL GAMBLING. PSYCHIATRY RES. 2009;167:161-168.