VISN 19 MIRECC Specialties: Substance Use Disorders (SUD)

Research, Education and Clinical Care Related to
Substance Use Disorders (SUD)

Research Projects

Development of an Intervention for Soldiers and Veterans with Co-Occurring Traumatic Brain Injury and Substance Use Disorders

Research Team: Deborah Yurgelun-Todd PhD, Elliott Bueler

Purpose: To design a novel substance abuse intervention and related treatment manual for individuals who served in the military and have co-occurring mild TBI and substance use disorders.

Keywords: Evidence-Based Treatments, Substance Use Disorders (SUD), Traumatic Brain Injury (TBI)

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Neurobiology of Suicide Risk in Traumatic Brain Injury and Substance Abuse

Research Team: Deborah Yurgelun-Todd PhD, Elliott Bueler

Traumatic brain injury is an important medical problem for Veterans. Individuals with traumatic brain injuries are at increased risk for various psychiatric problems, including those associated with suicide. This study seeks to better understand the relationship between these factors.

Keywords: Evidence-Based Treatments, Suicide Prevention, Substance Use Disorders (SUD), Traumatic Brain Injury (TBI)

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Recent Presentations Related to Substance Use Disorders (SUD)

Substance Use Disorders and Suicide

5/5/11

Jennifer Olson-Madden PhD

Boulder Mental Health Center, Boulder, CO

Keywords: Substance Use Disorders (SUD), Suicide Prevention

PowerPoint | PDF 

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Recent Publications (since 2009)

Gruber, S.A., Rogowska, J., & Yurgelun-Todd, D.A. (2009) Altered affective response in marijuana smokers: and fMRI study. Drug and Alcohol Dependence, 105(1-2):139-53.

More than 94 million Americans have tried marijuana, and it remains the most widely used illicit drug in the nation. Investigations of the cognitive effects of marijuana report alterations in brain function during tasks requiring executive control, including inhibition and decision-making. Endogenous cannabinoids regulate a variety of emotional responses, including anxiety, mood control, and aggression; nevertheless, little is known about smokers' responses to affective stimuli. The anterior cingulate and amygdala play key roles in the inhibition of impulsive behavior and affective regulation, and studies using PET and fMRI have demonstrated changes within these regions in marijuana smokers. Given alterations in mood and perception often observed in smokers, we hypothesized altered fMRI patterns of response in 15 chronic heavy marijuana smokers relative to 15 non-marijuana smoking control subjects during the viewing of masked happy and fearful faces. Despite no between-group differences on clinical or demographic measures, smokers demonstrated a relative decrease in both anterior cingulate and amygdalar activity during masked affective stimuli compared to controls, who showed relative increases in activation within these regions during the viewing of masked faces. Findings indicate that chronic heavy marijuana smokers demonstrate altered activation of frontal and limbic systems while viewing masked faces, consistent with autoradiographic studies reporting high CB-1 receptor density in these regions. These data suggest differences in affective processing in chronic smokers, even when stimuli are presented below the level of conscious processing, and underscore the likelihood that marijuana smokers process emotional information differently from those who do not smoke, which may result in negative consequences.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Han, D. H., Hwang, J. W., & Renshaw, P. F. (2010) Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction. Experimental Clinical Psychopharmacology,18(4), 297-304.

Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (<3 days/week and <1 hr/day). At baseline and at the end of 6 weeks of bupropion SR treatment, brain activity in response to StarCraft cue presentation was assessed using 1.5 Tesla functional MRI. In addition, symptoms of depression, craving for playing the game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Han, D. H., Kim, Y. S., Lee, Y. S., Min, K. J., & Renshaw, P. F. (2010). Changes in cue-induced, prefrontal cortex activity with video-game play. Cyberpsychology, Behavior and Social Networking, 13(6), 655-661.

Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Lee, S. H., Han, D. H., Oh, S., Lyoo, I. K., Lee, Y. S., Renshaw, P.F., et al. (2009). Quantitative electroencephalographic (qEEG) correlates of craving during virtual reality therapy in alcohol-dependent patients. Pharmacology, Biochemistry & Behavior, 91(3), 393-397.

Virtual reality (VR) is an evolving technology that is being applied to treat a wide range of medical and psychiatric diseases. A virtual reality therapy (VRT) with multisensory stimulation has been applied to patients with alcohol dependence (ADP). We hypothesized that the VRTP for alcohol dependence would reduce the craving for alcohol and increase alpha wave activity in frontal areas of individuals with ADP. Twenty ADP and eighteen ADP were exposed to a series of 10 VRTP sessions (VRTP-ADP) and cognitive behavioral therapy (nVRTP-ADP), respectively. Fifteen healthy controls were exposed to VRTP for comparing the changes of craving and EEG during all three phases of VRTP. The VRTP-ADP exhibited a greater decrease in craving after the 10th VRTP session, when compared to the nVRTP-ADP. Compared to the healthy control subjects, VRTP-ADP group showed higher magnitude of the change in craving throughout VRTP sessions. These results suggest that VRTP may be useful as an adjunct to treating alcohol dependence but may also serve as an evaluation tool to identify high-risk patients.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Licata, S. C., & Renshaw, P.F. (2010). Neurochemistry of drug action: insights from proton magnetic resonance spectroscopic imaging and the relevance to addiction. Annals of the New York Academy of Sciences, 1187, 148-171.

Proton magnetic resonance spectroscopy ((1)H MRS) is a noninvasive imaging technique that permits measurement of particular compounds or metabolites within the tissue of interest. In the brain, (1)H MRS provides a snapshot of the neurochemical environment within a defined volume of interest. A search of the literature demonstrates the widespread utility of this technique for characterizing tumors, tracking the progress of neurodegenerative disease, and for understanding the neurobiological basis of psychiatric disorders. As of relatively recently, (1)H MRS has found its way into substance abuse research, and it is beginning to become recognized as a valuable complement in the brain imaging toolbox that also contains positron emission tomography, single-photon-emission computed tomography, and functional magnetic resonance imaging. Drug abuse studies using (1)H MRS have identified several biochemical changes in the brain. The most consistent alterations across drug class were reductions in N-acetylaspartate and elevations in myo-inositol, whereas changes in choline, creatine, and amino acid transmitters also were abundant. Together, the studies discussed herein provide evidence that drugs of abuse may have a profound effect on neuronal health, energy metabolism and maintenance, inflammatory processes, cell membrane turnover, and neurotransmission, and these biochemical changes may underlie the neuropathology within brain tissue that subsequently gives rise to the cognitive and behavioral impairments associated with drug addiction.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Liu X, Jensen JE, Gillis TE, Zuo CS, Prescot AP, Brimson M, Cayetano K, Renshaw PF, Kaufman MJ. Chronic cocaine exposure induces putamen glutamate and glutamine metabolite abnormalities in squirrel monkeys. Psychopharmacology (Berl). 2011 Oct;217(3):367-75. Epub 2011 Apr 15.

RATIONALE: Chronic cocaine exposure has been associated with progressive brain structural and functional changes. Clarifying mechanisms underlying cocaine's progressive brain effects may help in the development of effective cocaine abuse treatments. OBJECTIVES: We used a controlled squirrel monkey model of chronic cocaine exposure (45 mg/kg/week for 9 months) combined with ultra-high magnetic field (9.4 T) proton magnetic resonance spectroscopy to prospectively measure putamen metabolite changes. METHODS: Proton metabolites were measured with a STEAM sequence, quantified with LCModel using a simulated basis set, and expressed as metabolite/total creatine (tCr) ratios. RESULTS: We found cocaine-induced time-dependent changes in putamen glutamate/tCr and glutamine/tCr metabolite ratios suggestive of altered glutamate compartmentalization, neurotransmission, and metabolism. By contrast, saline-treated monkeys exhibited no metabolite changes over time. The time course of cocaine-induced metabolite abnormalities we detected is consistent with the apparent time course of glutamate abnormalities identified in a cross-sectional study in human cocaine users, as well as with microdialysis findings in rodent models of repeated cocaine exposure. CONCLUSIONS: Together, these findings suggests that this squirrel monkey model may be useful for characterizing glutamatergic changes associated with cocaine exposure and for determining efficacies of treatments designed to mitigate cocaine-induced glutamatergic system dysfunction.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Lopez-Larson, M. P., Bogorodzki, P., Rogowska, J., McGlade, E., King, J. B., Terry, J., & Yurgelun-Todd, D. (2011). Altered prefrontal and insular cortical thickness in adolescent marijuana users. Behavioral Brain Research, 220(1), 164-172.

INTRODUCTION: There are limited data regarding the impact of marijuana (MJ) on cortical development during adolescence. Adolescence is a period of substantial brain maturation and cortical thickness abnormalities may be indicative of disruptions of normal cortical development. This investigation applied cortical-surface based techniques to compare cortical thickness measures in MJ using adolescents compared to non-using controls. METHODS: Eighteen adolescents with heavy MJ use and 18 non-using controls similar in age received MRI scans using a 3T Siemens scanner. Cortical reconstruction and volumetric segmentation was performed with FreeSurfer. Group differences in cortical thickness were assessed using statistical difference maps covarying for age and gender. RESULTS: Compared to non-users, MJ users had decreased cortical thickness in right caudal middle frontal, bilateral insula and bilateral superior frontal cortices. Marijuana users had increased cortical thickness in the bilateral lingual, right superior temporal, right inferior parietal and left paracentral regions. In the MJ users, negative correlations were found between frontal and lingual regions for urinary cannabinoid levels and between age of onset of use and the right superior frontal gyrus. CONCLUSION: This is one of the first studies to evaluate cortical thickness in a group of adolescents with heavy MJ use compared to non-users. Our findings are consistent with prior studies that documented abnormalities in prefrontal and insular regions. Our results suggest that age of regular use may be associated with altered prefrontal cortical gray matter development in adolescents. Furthermore, reduced insular cortical thickness may be a biological marker for increased risk of substance dependence.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Olson-Madden, J., Brenner, L.A., Harwood, J. E., Emrick, C. D., Corrigan, J. D., & Thompson, C. (2010). Traumatic brain injury and psychiatric diagnoses in Veterans seeking outpatient substance abuse treatment. Journal of Head Trauma and Rehabilitation, 25(6), 470-479.

OBJECTIVES: Explore the incidence of traumatic brain injury (TBI) in veterans seeking outpatient substance abuse treatment and the association between TBI and psychiatric diagnoses. MAIN MEASURE: The Ohio State University TBI identification method (OSU TBI-ID) was administered to veterans with positive TBI-4 screens; substance-related and psychiatric diagnoses were extracted from the medical record. PARTICIPANTS: : Over an 18-month period, 247 veterans completed the TBI-4. Of the 136 who screened positive, 70 were administered the OSU TBI-ID. RESULTS: On the basis of the TBI-4, 55% (95% CI: 49%-61%) of veterans screened positive for a history of TBI. The OSU TBI-ID was used to confirm screening results. Those who completed the OSU TBI-ID sustained an average of 3.4 lifetime TBIs. For each additional TBI sustained, after initial injury, there was an estimated 9% increase in the number of psychiatric diagnoses documented (99% CI: 1%-17%). For each additional documented psychiatric diagnosis, there was an estimated increase of 11% in the number of injuries sustained (99% CI: 1%-22%). Also, 54% (38/70) had a positive history of TBI prior to adulthood. CONCLUSION: These results emphasize the need for TBI screening in this vulnerable population, as well as the importance of increasing brain injury awareness among those abusing substances and their care providers. These findings also highlight the need for specialized services for those with TBI and co-occurring substance misuse aimed at decreased future TBIs or negative psychiatric outcomes or both. Further study is needed to clarify best practices.

Keywords: Traumatic Brain Injury (TBI), Substance Use Disorders (SUD)

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Ribeiro JD, Pease JL, Gutierrez PM, Silva C, Bernert RA, Rudd MD, Joiner TE Jr. Sleep problems outperform depression and hopelessness as cross-sectional and longitudinal predictors of suicidal ideation and behavior in young adults in the military. J Affect Disord. 2012 Feb;136(3):743-50.

Background: Sleep problems appear to represent an underappreciated and important warning sign and risk factor for suicidal behaviors. Given past research indicating that disturbed sleep may confer such risk independent of depressed mood, in the present report we compared self-reported insomnia symptoms to several more traditional, well-established suicide risk factors: depression severity, hopelessness, PTSD diagnosis, as well as anxiety, drug abuse, and alcohol abuse symptoms.

Methods: Using multiple regression, we examined the cross-sectional and longitudinal relationships between insomnia symptoms and suicidal ideation and behavior, controlling for depressive symptom severity, hopelessness, PTSD diagnosis, anxiety symptoms, and drug and alcohol abuse symptoms in a sample of military personnel (N=311).

Results: In support of a priori hypotheses, self-reported insomnia symptoms were crosssectionally associated with suicidal ideation, even after accounting for symptoms of depression, hopelessness, PTSD diagnosis, anxiety symptoms and drug and alcohol abuse. Selfreported insomnia symptoms also predicted suicide attempts prospectively at one-month follow up at the level of a non-significant trend, when controlling for baseline self-reported insomnia symptoms, depression, hopelessness, PTSD diagnosis and anxiety, drug and alcohol abuse symptoms. Insomnia symptoms were unique predictors of suicide attempt longitudinally when only baseline self-reported insomnia symptoms, depressive symptoms and hopelessness were controlled.

Limitations: The assessment of insomnia symptoms consisted of only three self-report items. Findings may not generalize outside of populations at severe suicide risk. Conclusions: These findings suggest that insomnia symptoms may be an important target for suicide risk assessment and the treatment development of interventions to prevent suicide.

Keywords: Suicide, PTSD, Substance Use Disorders (SUD) 

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Sava, S., McCafrey, A. M., & Yurgelun-Todd, D. A. (2009). Cognitive Neuroscience. Women and Addiction. Sudie Black, Guilford Publications pp 133-146.

No abstract available.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Silveri, M. M., Jensen, J. E., Rosso, I. M., Sneider, J. T., & Yurgelun-Todd, D.A. (2011). Preliminary evidence for white matter metabolite differences in marijuana-dependent young men using 2D J-resolved magnetic resonance spectroscopic imaging at 4 Tesla. Psychiatry Research, 191(3), 201-211.

Chronic marijuana (MRJ) use is associated with altered cognition and mood state, altered brain metabolites, and functional and structural brain changes. The objective of this study was to apply proton magnetic resonance spectroscopic imaging (MRSI) to compare proton metabolite levels in 15 young men with MRJ dependence and 11 healthy non-using (NU) young men. Spectra were acquired at 4.0 Tesla using 2D J-resolved MRSI to resolve coupled resonances in J-space and to quantify the entire J-coupled spectral surface of metabolites from voxels containing basal ganglia and thalamus, temporal and parietal lobes, and occipital white and gray matter. This method permitted investigation of high-quality spectra for regression analyses to examine metabolites relative to tissue type. Distribution of myo-inositol (mI)/creatine (Cr) was altered in the MRJ group whereas the NU group exhibited higher mI/Cr in WM than GM, this pattern was not observed in MRJ subjects. Significant relationships observed between global mI/Cr and distribution in WM, and self-reported impulsivity and mood symptoms were also unique between MRJ and NU groups. These preliminary findings suggest that mI, and distribution of this glial metabolite in WM, is altered by MRJ use and is associated with behavioral and affective features reported by young MRJ-dependent men.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Silveri, M. M., Rogowska, J., McCaffrey, A., & Yurgelun-Todd, D. (2011). Adolescents at risk for alcohol abuse demonstrate altered frontal lobe activation during Stroop performance. Alcoholism: Clinical & Experimental Research, 35(2), 218-228.

BACKGROUND: Children and adolescents, family history positive (FH+) for alcoholism, exhibit differences in brain structure and functional activation when compared to family history negative (FH-) counterparts. Given that frontal brain regions, and associated reciprocal connections with limbic structures, undergo the most dramatic maturational changes during adolescence, the objective of this study was to compare functional brain activation during a frontally mediated test of response inhibition in 32 adolescents separated into low-risk (FH-) and high-risk (FH+) groups. METHODS: Functional magnetic resonance (fMRI) blood oxygen level-dependent data were acquired at 1.5 Tesla during performance of Stroop Color Naming, Word Reading, and Interference. Preprocessing and statistical analyses, covaried for age, were conducted in SPM99 using a search territory that included superior, middle, and inferior frontal gyri (trigone region), anterior cingulate gyrus (CG), and left and right amygdala. RESULTS: Significantly greater activation in the fronto-limbic search territory was observed in FH+ relative to FH- subjects during Stroop Interference. In addition, a significant regression between brain activation and family history density was observed, with a greater density being associated with increased activation in regions including middle frontal gyrus (BA9) and CG (BA24). CONCLUSIONS: These data demonstrate a significant influence of FH status on brain activation during the performance of a response inhibition task, perhaps reflecting a neurobiological vulnerability associated with FH status that may include reduced neuronal efficiency and/or recruitment of additional neuronal resources. These findings are important given that the adolescent developmental period is already associated with reduced inhibitory capacity, even prior to the onset of alcohol use.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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Trksak, G. H., Jensen, J. E., Plante, D. T., Penetar, D. M., Tartarini, W. L., Maywalt, M. A., Brendel, M., Dorsey, C. M., Renshaw, P.F., & Lukas, S. E. (2010). Effects of sleep deprivation on sleep homeostasis and restoration during methadone-maintenance: a [31]P MRS brain imaging study. Drug and Alcohol Dependence,106(2-3), 79-91.

Insomnia afflicts many individuals, but particularly those in chronic methadone treatment. Studies examining sleep deprivation (SD) have begun to identify sleep restoration processes involving brain bioenergetics. The technique ([31])P magnetic resonance spectroscopy (MRS) can measure brain changes in the high-energy phosphates: alpha-, beta-, and gamma-nucleoside triphosphate (NTP). In the present study, 21 methadone-maintained (MM) and 16 control participants underwent baseline (BL), SD (40 wakeful hours), recovery1 (RE1), and recovery2 (RE2) study nights. Polysomnographic sleep was recorded each night and ([31])P MRS brain scanning conducted each morning using a 4T MR scanner (dual-tuned proton/phosphorus head-coil). Interestingly, increases in total sleep time (TST) and sleep efficiency index (SEI) commonly associated with RE sleep were not apparent in MM participants. Analysis of methadone treatment duration revealed that the lack of RE sleep increases in TST and SEI was primarily exhibited by short-term MM participants (methadone 12 months) participants was more comparable to control participants. Slow wave sleep increased during RE1, but there was no difference between MM and control participants. Spectral power analysis revealed that compared to control participants; MM participants had greater delta, theta, and alpha spectral power during BL and RE sleep. ([31])P MRS revealed that elevations in brain beta-NTP (a direct measure of ATP) following RE sleep were greater in MM compared to control participants. Results suggest that differences in sleep and brain chemistry during RE in MM participants may be reflective of a disruption in homeostatic sleep function.

Keywords: Brain & Biology, Substance Use Disorders (SUD)

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