Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation

Overview

Journal J Addict Res Ther

Date 2016 Oct 4

PMID 27695638

Citations 9

Authors

Donna E Murray

Timothy C Durazzo

Thomas P Schmidt

Christoph Abe

Joseph Guydish

Dieter J Meyerhoff

Affiliations

Soon will be listed here.

Abstract

Objective: Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.

Methods: Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.

Results: Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.

Conclusion: The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment.

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References

Pennington D, Durazzo T, Schmidt T, Abe C, Mon A, Meyerhoff D . Alcohol use disorder with and without stimulant use: brain morphometry and its associations with cigarette smoking, cognition, and inhibitory control. PLoS One. 2015; 10(3):e0122505. PMC: 4372577. DOI: 10.1371/journal.pone.0122505. View

Greenwald M, Woodcock E, Khatib D, Stanley J . Methadone maintenance dose modulates anterior cingulate glutamate levels in heroin-dependent individuals: A preliminary in vivo (1)H MRS study. Psychiatry Res. 2015; 233(2):218-24. DOI: 10.1016/j.pscychresns.2015.07.002. View

Hermann D, Sartorius A, Welzel H, Walter S, Skopp G, Ende G . Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biol Psychiatry. 2007; 61(11):1281-9. DOI: 10.1016/j.biopsych.2006.08.027. View

Silveri M, Jensen J, Rosso I, Sneider J, Yurgelun-Todd D . Preliminary evidence for white matter metabolite differences in marijuana-dependent young men using 2D J-resolved magnetic resonance spectroscopic imaging at 4 Tesla. Psychiatry Res. 2011; 191(3):201-11. PMC: 3065822. DOI: 10.1016/j.pscychresns.2010.10.005. View

Meyerhoff D, Durazzo T, Ende G . Chronic alcohol consumption, abstinence and relapse: brain proton magnetic resonance spectroscopy studies in animals and humans. Curr Top Behav Neurosci. 2011; 13:511-40. DOI: 10.1007/7854_2011_131. View

Lejuez C, Read J, Kahler C, Richards J, Ramsey S, Stuart G . Evaluation of a behavioral measure of risk taking: the Balloon Analogue Risk Task (BART). J Exp Psychol Appl. 2002; 8(2):75-84. DOI: 10.1037//1076-898x.8.2.75. View

Darke S, McDonald S, Kaye S, Torok M . Comparative patterns of cognitive performance amongst opioid maintenance patients, abstinent opioid users and non-opioid users. Drug Alcohol Depend. 2012; 126(3):309-15. DOI: 10.1016/j.drugalcdep.2012.05.032. View

HOLMAN B, Carvalho P, Mendelson J, Teoh S, NARDIN R, Hallgring E . Brain perfusion is abnormal in cocaine-dependent polydrug users: a study using technetium-99m-HMPAO and ASPECT. J Nucl Med. 1991; 32(6):1206-10. View

Stinson F, Grant B, Dawson D, Ruan W, Huang B, Saha T . Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Depend. 2005; 80(1):105-16. DOI: 10.1016/j.drugalcdep.2005.03.009. View

10.

Sobell L, Sobell M, Riley D, Schuller R, Pavan D, Cancilla A . The reliability of alcohol abusers' self-reports of drinking and life events that occurred in the distant past. J Stud Alcohol. 1988; 49(3):225-32. DOI: 10.15288/jsa.1988.49.225. View

11.

Yuan Y, Zhu Z, Shi J, Zou Z, Yuan F, Liu Y . Gray matter density negatively correlates with duration of heroin use in young lifetime heroin-dependent individuals. Brain Cogn. 2009; 71(3):223-8. DOI: 10.1016/j.bandc.2009.08.014. View

12.

Meyerhoff D, Bloomer C, Schuff N, Ezekiel F, Norman D, Clark W . Cortical metabolite alterations in abstinent cocaine and cocaine/alcohol-dependent subjects: proton magnetic resonance spectroscopic imaging. Addict Biol. 2010; 4(4):405-19. PMC: 2893339. DOI: 10.1080/13556219971399. View

13.

Van Leemput K, Maes F, Vandermeulen D, Suetens P . Automated model-based tissue classification of MR images of the brain. IEEE Trans Med Imaging. 2000; 18(10):897-908. DOI: 10.1109/42.811270. View

14.

Volkow N, Fowler J, Wang G . The addicted human brain: insights from imaging studies. J Clin Invest. 2003; 111(10):1444-51. PMC: 155054. DOI: 10.1172/JCI18533. View

15.

Durazzo T, Meyerhoff D, Mon A, Abe C, Gazdzinski S, Murray D . Chronic Cigarette Smoking in Healthy Middle-Aged Individuals Is Associated With Decreased Regional Brain N-acetylaspartate and Glutamate Levels. Biol Psychiatry. 2015; 79(6):481-8. PMC: 4600002. DOI: 10.1016/j.biopsych.2015.03.029. View

16.

Loeber S, Nakovics H, Kniest A, Kiefer F, Mann K, Croissant B . Factors affecting cognitive function of opiate-dependent patients. Drug Alcohol Depend. 2011; 120(1-3):81-7. DOI: 10.1016/j.drugalcdep.2011.07.001. View

17.

Haselhorst R, Dursteler-MacFarland K, Scheffler K, Ladewig D, Muller-Spahn F, Stohler R . Frontocortical N-acetylaspartate reduction associated with long-term i.v. heroin use. Neurology. 2002; 58(2):305-7. DOI: 10.1212/wnl.58.2.305. View

18.

Hermann D, Frischknecht U, Heinrich M, Hoerst M, Vollmert C, Vollstadt-Klein S . MR spectroscopy in opiate maintenance therapy: association of glutamate with the number of previous withdrawals in the anterior cingulate cortex. Addict Biol. 2011; 17(3):659-67. DOI: 10.1111/j.1369-1600.2010.00290.x. View

19.

Schuff N, Ezekiel F, Gamst A, Amend D, Capizzano A, Maudsley A . Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging. Magn Reson Med. 2001; 45(5):899-907. PMC: 1851682. DOI: 10.1002/mrm.1119. View

20.

El-Sheikh S, Bashir T . High-risk relapse situations and self-efficacy: comparison between alcoholics and heroin addicts. Addict Behav. 2004; 29(4):753-8. DOI: 10.1016/j.addbeh.2004.02.003. View