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 • 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. Evenden, 1999b, de Wit, 2009
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 medial prefrontal/cingulate circuit is critical for feedback monitoring and motivation, with lesions producing profound apathy. The dlPFC and OFC is associated with behavioral regulation owing to its unique capacity to maintain and integrate sensory, affective, and associative information.
• 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. 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. Balleine and Killcross, 2006
• 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.
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