The non-medical use of prescription stimulants and use of methamphetamine continues to be prevalent among young adults and is an enormous public health problem. As many as 1 in 10 American young adults aged 16?25 years reported misuse of stimulants in their lifetime and 1 out of 7 of these individuals develop stimulant dependence. This proposal aims to continue ongoing work to identify which brain processing differences predict transition from occasional stimulant use to dependence. Our main findings have been: (1) Attenuated insula response during risk taking, which may be related to reduced interoceptive signaling;(2) Increased prefrontal activation in the presence of equal inhibitory performance, which implies inefficient inhibitory processing. (3) Reduced modulation of striatum to different levels of errors in decision situations. However, we have also found significant heterogeneity among stimulant users depending on the context in which stimulant use takes place that point towards opposite processing differences in ?partiers? versus ?studiers?. The fundamental hypothesis proposed here is that stimulant users at highest risk for transition to dependence exhibit an increased propensity to take risks because of attenuated processing in risk-related brain structures. We propose that this is due to the fact that the insular cortex of these individuals does not signal as effectively potentially aversive outcomes (in terms of internal body states). The two specific aims are: (1) To determine neural processing differences in cohort 1 across individuals who develop dependence and those who do not. This the longitudinal component of the first cohort study, which will not include an fMRI experiment for a subset of n=60 cohort 1 individuals. (2) To investigate a new prospective cohort 2 of 60?studiers? and 60 ?partiers? focused on altered decision-making and interoceptive processing. This is both a cross-sectional and a 3-y follow-up study to examine the hypothesis that ?partiers? but not ?studiers? are at a high risk of transitioning to dependence. This competitive renewal seeks to address two practical questions: (1) ?can neuroimaging be used as a predictive marker?? and (2) ?is there dysfunction of the interoceptive system which could be a target for intervention, e.g. using real-time fMRI??

Public Health Relevance

This project seeks to understand the brain processes that put young adults at risk for stimulant dependence. We hypothesize that stimulant users are driven to make non-optimally decision because of the way they feel inside. We want to test this hypothesis by comparing individuals who have developed problems versus this that have stopped using stimulants from the stimulant users we have studied over the last five years.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA016663-06
Application #
7654023
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Grant, Steven J
Project Start
2003-07-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
6
Fiscal Year
2009
Total Cost
$493,709
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Stewart, Jennifer L; Butt, Mamona; May, April C et al. (2017) Insular and cingulate attenuation during decision making is associated with future transition to stimulant use disorder. Addiction 112:1567-1577
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Harlé, Katia M; Zhang, Shunan; Ma, Ning et al. (2016) Reduced Neural Recruitment for Bayesian Adjustment of Inhibitory Control in Methamphetamine Dependence. Biol Psychiatry Cogn Neurosci Neuroimaging 1:448-459
Gowin, Joshua L; Ball, Tali M; Wittmann, Marc et al. (2015) Individualized relapse prediction: Personality measures and striatal and insular activity during reward-processing robustly predict relapse. Drug Alcohol Depend 152:93-101
Stewart, Jennifer L; May, April C; Tapert, Susan F et al. (2015) Hyperactivation to pleasant interoceptive stimuli characterizes the transition to stimulant addiction. Drug Alcohol Depend 154:264-70

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