understanding the impact of cigarette smoking using brain ... · •overview of neurocircuitry...
TRANSCRIPT
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Angelica Morales, PhD
Postdoctoral Fellow
Developmental Brain Imaging Lab
Oregon Health & Science University
Understanding the Impact of Cigarette Smoking
Using Brain Imaging
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No Financial Disclosures
The presenter: Angelica Morales, PhD has no financial disclosures.
The planning committee: Bita Moghaddam, PhD; Liz Stevenson, JD, MPH; William Wilson, MD; Neisha D’Souza, MD; Sean Stanley, MD;
Micaela Sandoval, MBA, and Kevin Howden have no financial disclosures.
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Objectives
• Identify current trends in cigarette use in the United States
• Overview of neurocircuitry implicated in substance use disorders
• Examine the evidence indicating that cigarette use is associated with abnormalities in brain structure and function in adolescent, young adult and adult smokers
• Review the association between neurobiology and response to nondrug rewards and cigarette craving
• Discuss how light and intermittent smokers differ from daily smokers
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Current Cigarette Smoking Trends
MMWR, 2016
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Risks Associated with Cigarette Use
• Leading cause of preventable death in the US
• Associated with 480,000 deaths per year
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Benefits of Smoking Cessation
Pirie et al., 2013
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Smoking Cessation is Difficult
MMWR, 2017
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• Some studies indicated that persons who start smoking at an early age are more likely to become life-long smokers and are more susceptible to nicotine addiction than adults (White et al. 2009)
• Maturational brain processes continue through early adulthood (Paus2005)
Smoking Cessation is Difficult
Gogtay et al., 2004
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• Some studies indicated that persons who start smoking at an early age are more likely to become life-long smokers and are more susceptible to nicotine addiction than adults (White et al. 2009)
• Maturational brain processes continue through early adulthood (Paus 2005)
• Tobacco use during this critical period produces neurobiological changes that promote tobacco dependence later in life (Tiffany 2008)
Smoking Cessation is Difficult
Gogtay et al., 2004
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Koob and Volkow, 2016
Development of Substance Use Disorders
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Development of Substance Use Disorders
• Nicotine reaches the brain seconds after cigarette smoking
• Nicotine binds to nicotinic acetylcholine receptors
• Release of various neurotransmitters including dopaminewhich is associated with reward/pleasure
Koob and Volkow, 2016
BBC, 2007
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Development of Substance Use Disorders
• Cigarette use becomes paired with situations surrounding use
• Drug-associated stimuli can trigger dopamine release
• Dopamine release in response to smoking cues may motivate drug seeking behavior by increasing craving
• Cue-induced craving is intense, acute, and episodic urge to use drugs
Koob and Volkow, 2016
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Development of Substance Use Disorders
• Chronic drug use produces neuroadaptations that result in withdrawal symptoms
• Smoke throughout the day to maintain levels of nicotine elevated and avoid symptoms of nicotine withdrawal
Koob and Volkow, 2016
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Symptoms of Nicotine Withdrawal
• Anxiety
• Depression
• Difficulty Concentrating
• Impaired Performance
• Increased appetite and weight gain
• Irritability, frustration, and anger
• Restlessness and impatience
• Sleep disturbances
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Development of Substance Use Disorders
• Chronic drug use produces neuroadaptations that result in withdrawal symptoms
• Smoke throughout the day to maintain levels of nicotine elevated and avoid symptoms of nicotine withdrawal
• Reduction in sensitivity of the brain reward system to nondrug rewards
Koob and Volkow, 2016
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Development of Substance Use Disorders
• Seek substances after abstinence
• Background or tonic craving• Slowly change state
• Induced by abstinence
• Fades over time
• Insula – integrates information about motivation and emotion with interoceptive information
• Prefrontal cortex – cognitive control over tonic and cue-induced craving
Koob and Volkow, 2016
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Brain function and Structure are Associated with Cigarette Craving, Craving Regulation, and Reward Processing
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Task-based functional MRI
Fox and Raichel, 2007Time in seconds
fMRI measures brain activation by indexing changes in blood oxygenation that result from changes in neuronal activity
Eyes Open > Closed
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Assessing Cue-Induced Craving
Smolka et al., 2006
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Exposure to Smoking Cues Increases Brain Activation
David et al, 2005
Control > SmokerSmoking Cues > Neutral Cues
Smoking Cues > Neutral Cues
Engelmann et al, 2005
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Brain Activation During Cue-Induced Craving Correlates with the Subject Experience
Brody et al., 2007
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Brain Reactivity to Smoking Cues Predicts Treatment Outcomes
Janes et al., 2010
Subjects who slipped showed greater brain activation to smoking vs neutral images
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Craving Regulation
• Loss of control over craving contributes to compulsive drug taking
• Treatment strategies help identify and regulate craving
• Cognitive Behavioral Therapy – Use cognitive strategies such as focusing on the long term consequences of smoking• “If I smoke this cigarette my lungs will fill with tar”
• Mindfulness Based Interventions – Notice craving and accept them as they are• “Craving is impermanent and I don’t have to act on it or avoid it”
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• NOW = respond naturally and focus on immediate response
• LATER = the about the negative consequences associated with drug use or eating
Craving Regulation
Kober et al., 2010
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Cognitive Strategies for Craving Regulation
Kober et al., 2010
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Mindfulness-Based Regulation
• LOOK = view the picture as naturally as possible
• MINDFULLY ATTEND = focus on their responses to the picture while maintaining a nonjudgmental attitude toward those responses
LOOKor
MINDFULLY ATTEND
Strength of Craving
Westbrook et al., 2013
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Mindful attention reduced self-reported cigarette craving in response to cues
Westbrook et al., 2013
Less mPFC activity during mindful attention Less mPFC connectivity during mindful attention
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Resting State Functional Connectivity to Assess Abstinence-Induced Craving
Identifies the functional organization of brain systems by
measuring temporal correlations of intrinsic brain activity
Uncorrelated Activity Correlated Activity
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Connectivity of the anterior insula in adult cigarette smokers
Seed Region
Stoeckel et al., 2015
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Abstinence Induced-Craving In Young Adults
Bi et al., 2017
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Brain Structure and Craving
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Structural Abnormalities in Adult Smokers
Fritz et al., 2014 Morales et al., 2012 Franklin et al., 2014
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Greater Striatal Volume Associated with Greater Abstinence-Induced Craving
Janes et al., 2015
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Rig
ht V
en
tra
l An
terio
r In
su
la
Th
ickn
ess (
mm
)
Cigarette Dependence
CDS-12 ScoreUrge to Smoke
CDS Item 5
r = -0.653
p = 0.003
r = -0.593
p = 0.010
Brain Structure Relates to Abstinence-Induced Cigarette Craving in Young Adults
Morales et al., 2014
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Craving and Craving Regulation: Take Home Points
• Abstinence-induced and cue-induced craving are related to abnormalities in brain structure and function in brain regions implicated in interoceptiveawareness, reward processing, and executive functioning
• Longitudinal studies are needed to determine whether structural and functional abnormalities observed in adolescents or young adults reflect pre-existing risk factors for substance use or a consequence of drug use
• Different craving regulation strategies may rely on different neurobiological mechanisms
• More research is needed to determine whether individual differences in neurobiology influence the success of various craving reduction strategies
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Measuring Neurobiological Response to Monetary Reward in Smokers
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Blunted Mesocorticolimbic Responses During Reward Anticipation in Adult Smokers
Wilson et al., 2014Fedota et al., 2015
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Nondrug Reward Processing in Adolescent Smokers
Peters et al., 2011
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Nondrug Reward Processing:Take Home Points
• Smokers show blunted neurobiological responses in mesolimbic circuitry in response to nondrug reward
• The potent response to cigarette use may bias the individual toward smoking behavior
• Pre-existing risk factor for various from of psychopathology?
• In adolescents, prospective studies show that blunted mesolimbic responses during reward anticipation predict future symptoms of depression (Morgan et al., 2013) and anxiety (Forbes et al., 2010)
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Current Cigarette Smoking Trends
MMWR, 2016
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Current Cigarette Smoking Trends
MMWR, 2016
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Defining Light / Intermittent Smoking
• No consistent definition• Light Smokers – smoke daily but smoke few cigarettes per day
• Occasional / Nondaily Smokers – smoke fewer than 30 days a month
• Social Smoker – nondaily smoking limited to social contexts
• Who is engaging in light / intermittent smoking?• Young
• Educated
• Women
• Minorities
Schane et al., 2010
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Increased Prevalence of Light / Intermittent Smoking
• Smoking bans in public places
• Increased price of cigarettes
• Increased in initiation of smoking among those over the age of 19
• Perception of harm
Institute of Medicine, 2007 Adapted from Amrock et al, 2015
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Negative Consequencesof Light / Intermittent Smoking
• Light and intermittent smoking increases risk for:• Cardiovascular disease (occasional smoking)• Cancer• Respiratory Diseases• Other disease (e.g. reproductive issues)• All cause mortality
• Nondaily smokers and social smokers may not self-identify as smokers and are not likely to perceive a need to quit
• Understanding the ways in which nondaily smokers are similar to and different from daily and non-smokers is important for the development of targeted interventions.
Schane et al, 2010
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Smoking Motives AmongIntermittent Smokers
• With abstinence intermittent smokers experience fewer symptoms of craving and withdrawal than daily smokers (Shiffman et al., 2015)
• Adult intermittent smokers are less likely to make quit attempts and 73-82% fail in their attempts (Tindle et al., 2011)
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Smoking Motives AmongIntermittent Smokers
Koob and Volkow, 2016
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Smoking Motives AmongIntermittent Smokers
• With abstinence intermittent smokers experience fewer symptoms of craving and withdrawal than daily smokers (Shiffman et al., 2015)
• Adult intermittent smokers are less likely to make quit attempts and 73-82% fail in their attempts (Tindle et al., 2011)
• Among intermittent smokers, cigarette use more strongly associated with situational triggers (Shiffman et al., 2014): • Being away from home• Social interaction• Others smoking• Drinking alcohol
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Strong Association Between Alcohol and Nondaily Cigarette Use Among Young Adults
• Nondaily smokers are more likely to engage in hazardous drinking (Harrison et al., 2008)
• The majority of smoking occasions occur under the influence of alcohol (McKee et al., 2004)
• Smoking typically occurs after 2-3 drinks suggesting that the effects of alcohol intoxication promote cigarette use (Harrison et al., 2008)
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Acute Alcohol Intoxication Increases Cigarette Craving in Nondaily Smokers
King et al., 2010
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Alcohol Intoxication Increases NAcc Response to Cigarette Cues in Young Nondaily Smokers
King et al., 2010
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What factors determine future cigarette use?
• Smoking patterns are unstable during young adulthood (Caldeira et al., 2012)
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Cigarette Smoking Trajectories Among College Students
Caldeira et al., 2012
Nu
mb
er
of
smo
kin
g d
ays
in t
he
pas
t m
on
thHigh Stable
Low-increasing
High-decreasing
Low-stable
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What factors determine future cigarette use?
• Smoking patterns are unstable during young adulthood (Caldeira et al., 2012)
• Individual differences in response to smoking cues during placebo?
• Individual differences in response to smoking cues during alcohol intoxication? With friends?
• Responses to nondrug rewards?
• No existing longitudinal studies
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Drug vs Nondrug Reward Processingin Adult Occasional Smokers
Buhler et al., 2010
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Occasional Smokers Have Stronger Responses to Nondrug Rewards
Buhler et al., 2010
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Drug vs Nondrug Reward Processingin Occasional Smokers
Buhler et al., 2010
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Light / Intermittent Cigarette Use:Take Home Points
• We need to raise awareness about the health risks of ANY smoking
• Since nondaily smokers and social smokers may not self-identify as smokers, clinicians may want ask “Do you use any tobacco products on a daily, weekly, or on a social basis?”
• Behavior modification techniques which focus on situational cues, such as alcohol use, may be useful with curbing cigarette use among nondaily smokers
• More research is necessary to understand the neurobiological markers that promote risk and resilience for varies trajectories of future cigarette use among young adults
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If you have general comments or appreciation for the speaker, they will be available after the program to speak with individuals.
EVAL SURVEY FOR CME CREDIT: https://www.surveymonkey.com/r/CTH7X3S