Research Portfolio

Funding Opportunities

Join our Mailing List
Join our mailing list to be notified of new funding opportunities.

Your Email

To receive information about funding opportunities, events, and program updates.



Brain metabolic changes with cigarette craving

Institution: Brentwood Biomedical Research Institute
Investigator(s): Arthur Brody, M.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7KT-0098 Award: $250,850
Subject Area: Nicotine Dependence
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
Smoking cigarettes substantially increases the risk of heart attack, stroke, and other severe medical conditions. Craving for cigarettes in smokers attempting to quit has repeatedly been associated with a relapse into usage. Current medications to treat dependence on cigarettes, such as the antidepressant bupropion (Zyban) and the nicotine patch or gum, are better than a sugar pill in reducing cigarette craving and relapse in the short term. However, only about 22% of smokers remain cigarette free after a year or two even with these treatments. Thus, there is a substantial need for better medications to treat addiction to cigarettes.

The goal of the study proposed here is to determine which areas of the brain become more active and which areas become less active when a smoker is craving cigarettes. We will also determine whether or not the whole brain becomes more or less active with cigarette craving. To do this, heavy smokers will be treated with either the antidepressant bupropion or a sugar pill. Subjects will then have brain scans while watching a nature video and also in a state of craving brought on by a brief period of abstinence from smoking and by seeing a video that reminds them of smoking. Clinical studies (including those done by our group at UCLA) have demonstrated that 3 to 5 hours of abstinence paired with seeing this video will reliably induce craving in smokers.

Recently, similar studies to the one proposed here have been done to examine which brain areas are activated in cocaine addicts during cocaine craving. In these studies, brain areas associated arousal and emotionality have been found to become more active when cocaine abusers are actively craving the drug. Examination of brain activity during cigarette craving has not yet been reported, and we will explore the idea that cigarette craving will activate brain regions similar to those activated by craving; for cocaine. We will also determine whether or not craving and brain changes are lessened in smokers treated with the medication bupropion when compared with smokers treated with a sugar pill Additionally, other aspects of cigarette withdrawal, such as anxiety, depression, and vital signs, will be measured to see if brain changes correlate with these factors.

In conjunction with other areas of research, brain imaging findings from this study may offer promising leads to develop better treatments for cigarette craving.

Final Report
Introduction: Craving for cigarettes in smokers attempting to quit has repeatedly been associated with relapse into usage. Current medications to treat dependence on cigarettes, such as the antidepressant bupropion (Zyban) and the nicotine patch or gum, are better than a sugar pill in reducing cigarette craving and relapse in the short term. However, only about 22% of smokers remain cigarette-free after a year or two, even when using these effective treatments. Thus, there is a substantial need for better medications to treat addiction to cigarettes. The goals of the studies performed here were to determine which areas of the brain become more active when smokers are craving cigarettes, and to determine the effect of a known effective treatment, bupropion (Zyban), on both cigarette cue-induced craving and brain activation associated with craving.

Topic Addressed: To study brain activity during craving, positron emission tomography (PET) brain scans were obtained in both smokers and nonsmokers (for comparison) while they were presented with neutral, nature-related videos and (in a separate session) when presented with cigarette-related videos (to induce cigarette craving). We also performed the same protocol in smokers following treatment with bupropion to see if subjects treated with this medication had attenuation of the craving induced by cigarette-related cues and also to determine if brain activation is attenuated in bupropion-treated smokers.

Progress Toward Specific Aims: Results from the first part of this study (comparing smokers with nonsmokers) indicate that several brain regions have changes in activity when smokers are craving cigarettes. Areas of the brain called the anterior cingulate gyrus, prefrontal cortex, and anterior temporal lobe (regions that are involved in anxiety and emotion) became more active while smokers were exposed to cigarette-related cues. Some of these regions, especially in the prefrontal cortex, correlated with the intensity of cigarette craving. These brain changes were also more strongly related to cigarette craving than to general anxiety.

Results from the second part of the study (comparing untreated smokers with bupropion-treated smokers) indicate that a course of treatment with bupropion attenuates the craving induced by cigarette-related cues. In addition, brain activation (of the anterior cingulate gyrus) in response to cigarette-related cues was attenuated in smokers treated with bupropion.

Future Direction and Impact: In conjunction with other areas of research, these brain imaging findings may offer promising leads to develop better treatments for cigarette craving and addiction to cigarettes. Other researchers are studying brain regions like the anterior cingulate gyrus, anterior temporal lobe, and prefrontal cortex to learn more about the chemicals within these structures and connections with other brain structures. Thus, identifying brain regions that mediate craving may lead to attempts to change these structures through medication or other therapy. In fact, our finding that bupropion attenuates craving and anterior cingulate gyrus activation indicates potential future medication targets for addiction to cigarettes.
Publications

Brain metabolic changes during cigarette craving
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Brody AL, Baxter LR, London ED, et al ABS
Yr: 1999 Vol: Nbr: Abs: 437 Pg:

Brain metabolic changes during cigarette craving
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Brody AL, London ED, Mandelkern MA, Childress AR, Ho ML, Lee GS, et al ART
Yr: 0 Vol: Nbr: Abs: Pg:

Functional brain alterations in depression and anxiety
Periodical: Psychiatric Times Monograph Index Medicus:
Authors: Brody AL ART
Yr: 1997 Vol: Nbr: Abs: Pg: 13 - 19

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder.
Periodical: British Journal of Psychiatry Index Medicus:
Authors: Saxena S, Brody AL, Schwartz JM, and Baxter LR ART
Yr: 1998 Vol: 173 Nbr: 35 Abs: Pg: 26 - 37

FDG-PET predictors of response to cognitive-behavioral therapy versus pharmacotherapy in obsessive-compulsive disorder.
Periodical: Psychiatry Research Neuroimaging Index Medicus:
Authors: Brody AL, Saxena S, Schwartz JM,Stoessel PW, Maidment K, Phelps ME, and Baxter LR ART
Yr: 1998 Vol: 84 Nbr: Abs: Pg: 1 - 6

Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.
Periodical: Neuropsychopharmacology Index Medicus:
Authors: Saxena S, Brody AL, Colgan M, Maidment KM, Dunkin JJ, Alborzian S, and Phelps ME ART
Yr: 1999 Vol: 21 Nbr: Abs: Pg: 683 - 693

Brain metabolic changes in major depressive disorder from pre- to post- treatment with paroxetine.
Periodical: Psychiatry Research Neuroimaging Index Medicus:
Authors: Brody AL, Saxena S, Silverman DHS, Fairbanks LA, Alborzian S, Et al ART
Yr: 1999 Vol: 91 Nbr: Abs: Pg: 127 - 139

Personality changes in adult subjects with major depressive disorder or obsessive-compulsive treated with paroxetine.
Periodical: Journal of Clinical Psychiatry Index Medicus:
Authors: Brody AL, Saxena S, Fairbanks L, Demaree H, Maidment KM, and Baxter LR ART
Yr: 2999 Vol: 61 Nbr: Abs: Pg: 349 - 355

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy.
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Brody AL, Saxena S, Stossel P, Gillies LA, Fairbanks LA, Alborzian S, et al ART
Yr: 2001 Vol: 58 Nbr: Abs: Pg: 631 - 640

Prefrontal-subcortical and limbic circuit mediation of major depressive disorder.
Periodical: Seminars Clinical Neuropsychiatry Index Medicus:
Authors: Brody AL, Barsom MW, Bota RG, and Saxena S ART
Yr: 2001 Vol: 6 Nbr: Abs: Pg: 102 - 112

Brain metabolic changes associated with symptom factor improvement in major depressive disorder.
Periodical: Biological Psychiatry Index Medicus:
Authors: Brody AL, Saxena S, Mandelkern MA, Fairbanks LA, Ho MK, and Baxter LR ART
Yr: 2001 Vol: 50 Nbr: Abs: Pg: 171 - 178

Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder versus major depressive disorder, occurring separately and concurrently.
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Saxena S, Brody AL, Alborzian S, Ho MK, Maidment KM, Huang SC, Wu HM, and Baxter LR ART
Yr: 2002 Vol: 59 Nbr: Abs: Pg: 250 - 261

A behaviorally-intensive V.A.-based smoking cessation program: 8 month adherence
Periodical: VA Health Systems Journal Index Medicus:
Authors: Leaf D, Brody AL, Kleinman L, McCreary C, and Wong G ART
Yr: 0 Vol: Nbr: Abs: Pg:

Brain-behavior relationships in obsessive-compulsive disorder.
Periodical: Seminars Clinical Neuropsychiatry Index Medicus:
Authors: Saxena S, Bota RG, and Brody AL ART
Yr: 0 Vol: Nbr: Abs: Pg:

Functional brain imaging in major depressive disorder.
Periodical: Southern California Psychiatrist Index Medicus:
Authors: Brody AL, and Saxena S ABS
Yr: 1999 Vol: 47 Nbr: Abs: Pg: 6