Neurobehavioral Regulation of Cigarette Cravings
Principal Investigator: Brian Hitsman
Abstract: This is a resubmission of a NIDA K08 Mentored Clinical Scientist Award. My career objective is to establish myself as independent investigator with a strong program of preclinical research focusing on the neurobiology of nicotine dependence and major depression. The application proposes a comprehensive, five-year program of supervised training and research with Raymond Niaura, Ph.D., and Lawrence H. Price, M.D., at Brown Medical School, and Marina Picciotto, Ph.D., and Tony P. George, M.D. at Yale School of Medicine. This multidisciplinary team will provide close guidance in a training plan comprised of structured didactics, seminars, and coursework in the Brown Brain Sciences Program and in the Department of Neuroscience at Yale University. The focus of the Research Plan is to characterize the neurobehavioral mechanisms that regulate cigarette cravings and smoking behavior among nicotine dependent individuals with and without vulnerability to major depression. In two double-blind, placebo-controlled challenge studies, acute tryptophan depletion (ATD) and alpha-methyl-para-tyrosine (AMPT) will be used to examine the effects of serotonin and dopamine depletion, respectively, on cravings and smoking topography. The specific aims are: (1) To examine the role of serotonin and dopamine in regulating cigarette cravings and smoking topography in depression vulnerable smokers; (2) To determine the relative effects of ATD and AMPT administration on individual differences in (obsessive craving, reward craving) and smoking topography; (3) To determine whether any changes in cue-induced cravings in response to ATD or AMPT administration correspond to changes in smoking topography; and (4) To explore whether associations among craving-related measures (e.g., obsessive and reward craving), smoking (e.g., topography, blood nicotine levels), and diagnostic group are mediated by changes in mood. Results of this research will increase understanding of the associations among serotonin and dopamine function, cue-induced cravings and vulnerability to major depression, and may have implications for tailoring pharmacological treatments to nicotine craving profiles.
Funding Period: 2004-09-30 - 2010-06-30
more information: NIH RePORT
- Elevated positive mood: a mixed blessing for abstinenceNeal Doran
Department of Psychology, University of Illinois at Chicago, Chicago, IL 60607, USA
Psychol Addict Behav 20:36-43. 2006..Results indicate that lower pretreatment PM may inhibit long-term cessation. Smokers with lower baseline PM may benefit from treatment that increases PM...
- Past major depression and smoking cessation outcome: a systematic review and meta-analysis updateBrian Hitsman
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Addiction 108:294-306. 2013..To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome...
- Accuracy of a brief screening scale for lifetime major depression in cigarette smokersBrian Hitsman
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA
Psychol Addict Behav 25:559-64. 2011..Smoking cessation trials that do not require a history of depressed mood and/or anhedonia for two weeks or longer may overestimate rates of lifetime MDE and confound tests of the association between depression and treatment outcome...
- Measuring smoking-related preoccupation and compulsive drive: evaluation of the obsessive compulsive smoking scaleBrian Hitsman
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA
Psychopharmacology (Berl) 211:377-87. 2010..Research on smokers is impeded, in part, by a lack of instruments that specifically measure compulsive smoking...
- Treatment of tobacco dependence in mental health and addictive disordersBrian Hitsman
Department of Preventive Medicine, Northwestern University, Chicago, Illinois 60611, USA
Can J Psychiatry 54:368-78. 2009....
- Acute tryptophan depletion and sweet food consumption by overweight adultsSherry L Pagoto
Department of Medicine, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Eat Behav 10:36-41. 2009..Lean participants' sweet calorie intake and food preference were unaffected by ATD. Findings suggest serotonergic involvement in the sweet food consumption by overweight individuals...
- Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health reportDouglas Ziedonis
University of Massachusetts Medical School and UMass Memorial Health Care, Worchester, MA01655, USA
Nicotine Tob Res 10:1691-715. 2008..Despite an accumulating literature for some specific psychiatric disorders and tobacco use and cessation, many unstudied research questions remain and are a focus and an emphasis of this review...
- Social support as a moderator of the relationship between recent history of depression and smoking cessation among lower-educated womenLindsey R Turner
Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, IL 60608, USA
Nicotine Tob Res 10:201-12. 2008..The determinants of successful quitting among lower-educated women differ between those who seek assistance and those who do not...
- A twin study of smoking, nicotine dependence, and major depression in menMichael Lyons
Department of Psychology, Boston University, Boston, MA 02215, USA
Nicotine Tob Res 10:97-108. 2008..Findings extend Kendler and colleague's (1993) study of female twins by demonstrating in men that shared genetic factors predispose not only to major depression and daily smoking but also to major depression and nicotine dependence...
- Effects of acute tyrosine/phenylalanine depletion on the selective processing of smoking-related cues and the relative value of cigarettes in smokersBrian Hitsman
Centers for Behavioral and Preventive Medicine, The Miriam Hospital and Brown Medical School, Coro Building, Suite 500, 1 Hoppin Street, Providence, RI 02903, USA
Psychopharmacology (Berl) 196:611-21. 2008..Acute tyrosine/phenylalanine depletion (ATPD) is a validated neurobiological challenge that results in reduced dopaminergic neurotransmission, allowing examination of the effects of a hypodopaminergic state on craving-related processes...
- Effects of progression to cigarette smoking on depressed mood in adolescents: evidence from the National Longitudinal Study of Adolescent HealthMarcus R Munafo
Department of Experimental Psychology, University of Bristol, Bristol, UK
Addiction 103:162-71. 2008..To investigate the relationship between smoking status and continuously distributed depressed mood among a cohort of adolescents...
- Social factors, psychopathology, and maternal smoking during pregnancyStephen E Gilman
Department of Society, Human Development, and Health, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
Am J Public Health 98:448-53. 2008..5%), compared with women with a college degree and without nicotine dependence (3.9%). More effective and accessible interventions for nicotine dependence among pregnant smokers are needed...
- Effect of tryptophan depletion on the attentional salience of smoking cuesBrian Hitsman
Centers for Behavioral and Preventive Medicine, Brown Medical School, The Miriam Hospital, Providence, RI, USA
Psychopharmacology (Berl) 192:317-24. 2007..There is increasing evidence linking cigarette craving and smoking behavior to serotonergic neurotransmission...
- Links between physical fitness and cardiovascular reactivity and recovery to psychological stressors: A meta-analysisKathleen Forcier
Centers for Behavioral and Preventive Medicine, Brown Medical School, Providence, RI 02906, USA
Health Psychol 25:723-39. 2006..Results have important implications for elucidating mechanisms underlying effects of fitness on cardiovascular disease and suggest that fitness may be an important confound in studies of stress reactivity...
- Effect of tryptophan depletion on smokers and nonsmokers with and without history of major depressionBonnie Spring
Medical Research, Hines Hospital, Veteran Affairs Medical Center, Hines, Illinois, USA
Biol Psychiatry 61:70-7. 2007..We tested whether acute tryptophan depletion (ATD) triggers depressive symptoms in euthymic, unmedicated smokers and nonsmokers with and without history of major depressive disorder (MDD)...
- Posttraumatic stress disorder and late-onset smoking in the Vietnam era twin registryKarestan C Koenen
Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, and The Miriam Hospital, Providence, RI, USA
J Consult Clin Psychol 74:186-90. 2006..If replicated, these results identify PTSD as a risk factor for smoking that should lead to early tobacco control treatment in this population...
- Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokersBrian Hitsman
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
Drug Alcohol Depend 130:135-41. 2013..The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome...