Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-24T01:35:57.393Z Has data issue: false hasContentIssue false

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence

Published online by Cambridge University Press:  25 July 2016

S. Tolomeo
Affiliation:
School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
S. Gray
Affiliation:
NHS Fife Research and Development Department, Queen Margaret Hospital, Dunfermline, UK
K. Matthews
Affiliation:
School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
J. D. Steele
Affiliation:
School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
A. Baldacchino*
Affiliation:
School of Medicine (Neuroscience), Ninewells Hospital and Medical School, University of Dundee, Dundee, UK St Andrews University, School of Medicine, St Andrews, UK
*
*Address for correspondence: A. Baldacchino, School of Medicine, Medical and Biological Science, North Haugh, St Andrews University, St Andrews, KY16 9TF, UK. (Email: [email protected])

Abstract

Background

Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare.

Method

The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50).

Results

Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain–thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group.

Conclusions

Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adinoff, B, Devous, MD, Best, SM, George, MS, Alexander, D, Payne, K (2001). Limbic responsiveness to procaine in cocaine-addicted subjects. American Journal of Psychiatry 158, 390398.CrossRefGoogle ScholarPubMed
Andersen, SN, Skullerud, K (1999). Hypoxic/ischaemic brain damage, especially pallidal lesions, in heroin addicts. Forensic Science International 102, 5159.CrossRefGoogle ScholarPubMed
Armbruster, DA, Krolak, JM (1992). Screening for drugs of abuse with the Roche ONTRAK assays. Journal of Analytical Toxicology 16, 172175.CrossRefGoogle ScholarPubMed
Ashburner, J, Friston, KJ (2005). Unified segmentation. NeuroImage 26, 839851.CrossRefGoogle ScholarPubMed
Baldacchino, A, Balfour, DJ, Matthews, K (2015). Impulsivity and opioid drugs: differential effects of heroin, methadone and prescribed analgesic medication. Psychological Medicine 45, 11671179.CrossRefGoogle ScholarPubMed
Baldacchino, A, Balfour, DJK, Passetti, F, Humphris, G, Matthews, K (2012). Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis. Neuroscience and Biobehavioral Review 36, 20562068.CrossRefGoogle ScholarPubMed
Clark, L, Robbins, TW, Ersche, KD, Sahakian, BJ (2006). Reflection impulsivity in current and former substance users. Biological Psychiatry 60, 515522.CrossRefGoogle ScholarPubMed
Dalley, JW, Everitt, BJ, Robbins, TW (2011). Impulsivity, compulsivity, and top-down cognitive control. Neuron 69, 680694.CrossRefGoogle ScholarPubMed
Daras, MD, Orrego, JJ, Akfirat, GL, Samkoff, LM, Koppel, BS (2001). Bilateral symmetrical basal ganglia infarction after intravenous use of cocaine and heroin. Clinical Imaging 25, 1214.CrossRefGoogle ScholarPubMed
Egan, PJ, Becker, FW, Bundt, R (2005). Bilateral pallidal infarction in sleep apnea syndrome (article in German). Nervenartz 76, 15391541.CrossRefGoogle Scholar
Ersche, KD, Fletcher, PC, Roiser, JP, Fryer, TD, London, M, Robbins, TW, Sahakian, BJ (2006). Differences in orbitofrontal activation during decision-making between methadone-maintained opioid users, heroin users and healthy volunteers. Psychopharmacology 188, 364373.CrossRefGoogle ScholarPubMed
Ersche, KD, Roiser, JP, Clark, L, London, M, Robbins, TW, Sahakian, BJ (2005). Punishment induces risky decision-making in methadone-maintained opioid users but not in heroin users or healthy volunteers. Neuropsychopharmacology 30, 21152124.CrossRefGoogle ScholarPubMed
Everitt, B, Belin, D, Economidou, D, Pelloux, Y, Dalley, J, Robbins, T (2008). Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philosophical Transactions of the Royal Society of London Series B: Biological Sciences 363, 31253135.CrossRefGoogle ScholarPubMed
Fagerstrom, K, Schneider, NG (1989). Measuring nicotine dependence: a review of the Fagerstrom Tolerance Questionnaire. Journal of Behavioral Medicine 12, 159182.CrossRefGoogle ScholarPubMed
Gradin, VB, Baldacchino, A, Balfour, D, Matthews, K, Steele, JD (2014). Abnormal brain activity during a reward and loss task in opiate-dependent patients receiving methadone maintenance therapy. Neuropsychopharmacology 39, 885894.CrossRefGoogle ScholarPubMed
Gurwell, JA, Nath, A, Sun, Q, Zhang, J, Martin, KM, Chen, Y, Hauser, KF (2001). Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro . Neuroscience 102, 555563.CrossRefGoogle ScholarPubMed
Harvey-Lewis, C, Perdrizet, J, Franklin, KBJ (2012). The effect of morphine dependence on impulsive choice in rats. Psychopharmacology 223, 477487.CrossRefGoogle ScholarPubMed
Koob, GF, Volkow, ND (2010). Neurocircuitry of addiction. Neuropsychopharmacology 35, 217238.CrossRefGoogle ScholarPubMed
Langevin, JP (2012). The amygdala as a target for behavior surgery. Surgical Neurology International 3 (Suppl. 1), S40S46.CrossRefGoogle ScholarPubMed
Liu, H, Hao, Y, Kaneko, Y, Ouyang, X, Zhang, Y, Xu, L, Xue, Z, Liu, Z (2009). Frontal and cingulate gray matter volume reduction in heroin dependence: optimized voxel-based morphometry. Psychiatry and Clinical Neuroscience 63, 563568.CrossRefGoogle ScholarPubMed
Lyoo, IK, Pollack, MH, Silveri, MM, Ahn, KH, Diaz, CI, Hwang, J, Kim, SJ, Yurgelun-Todd, DA, Kaufman, MJ, Renshaw, PF (2006). Prefrontal and temporal gray matter density decreases in opioid dependence. Psychopharmacology 184, 139144.CrossRefGoogle Scholar
Lyoo, IK, Streeter, CC, Ahn, KH, Lee, HK, Pollak, MH, Silveri, MM, Nassar, L, Levin, JM, Sarid-Segal, OM, Ciraulo, DA, Renshaw, PF, Kaufman, MJ (2004). White matter hyperintensities in subjects with cocaine and opiate dependence and healthy comparison subjects. Psychiatry Research 131, 135145.CrossRefGoogle ScholarPubMed
Lucassen, PJ, Pruessner, J, Sousa, N, Almeida, OF, Van Dam, AM, Rajkowska, G, Swaab, DF, Czéh, B (2014). Neuropathology of stress. Acta Neuropathologica 127, 109135.CrossRefGoogle ScholarPubMed
Madden, GJ, Petry, NM, Badger, GJ, Bickel, WK (1997). Impulsive and self-control choices in opioid-dependent patients and non-drug-using control patients: drug and monetary rewards. Experimental and Clinical Psychopharmacology 5, 256262.CrossRefGoogle ScholarPubMed
Marsden, J, Gossop, G, Stewart, D, Best, D, Farrell, M, Lehmann, P, Edwards, C, Strang, J (1998). The Maudsley Addiction Profile (MAP): a brief instrument for assessing treatment outcome. Addiction 93, 18571867.CrossRefGoogle ScholarPubMed
McKeganey, N, Bloor, M, Robertson, M, Neale, J, MacDougall, J (2006). Abstinence and drug abuse treatment: results from the Drug Outcome Research in Scotland study. Drugs Education, Prevention and Policy 13, 537550.CrossRefGoogle Scholar
Nelson, H, Willison, J (1991). The Revised National Adult Reading Test–Test Manual. NFER-Nelson: Windsor.Google Scholar
Ornstein, TJ, Iddon, JL, Baldacchino, AM, Sahakian, BJ, London, M, Everitt, BJ, Robbins, TW (2000). Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology 23, 113126.CrossRefGoogle ScholarPubMed
Patton, JH, Stanford, MS, Barratt, ES (1995). Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology 51, 768774.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Pattij, T, Schetters, D, Janssen, MC, Wiskerke, J, Schoffelmeer, AN (2009). Acute effects of morphine on distinct forms of impulsive behavior in rats. Psychopharmacology 205, 489502.CrossRefGoogle ScholarPubMed
Robbins, TW, Gillan, CM, Smith, DG, de Wit, S, Ersche, KD (2012). Neurocognitive endophenotypes of impulsivity and compulsivity: towards dimensional psychiatry. Trends in Cognitive Sciences 16, 8191.CrossRefGoogle ScholarPubMed
Rogers, RD, Everitt, BJ, Baldacchino, A, Blackshaw, AJ, Swainson, R, Wynne, K, Baker, NB, Hunter, J, Carthy, T, Booker, E, London, M (1999). Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opioid abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20, 322339.CrossRefGoogle ScholarPubMed
Rogers, RD, Robbins, TW (2001). Investigating the neurocognitive deficits associated with chronic drug misuse. Current Opinion in Neurobiology 11, 250257.CrossRefGoogle ScholarPubMed
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a Structured Diagnostic Psychiatric Interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59, 2233.Google ScholarPubMed
Slotnick, SD, Moo, LR, Segal, JB, Hart, J (2003). Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. Brain Research 17, 7582.Google ScholarPubMed
Strang, J, Babor, T, Caulkins, J, Fischer, B, Foxcroft, D, Humphreys, K (2012). Drug policy and the public good: evidence for effective interventions. Lancet 379, 7183.CrossRefGoogle ScholarPubMed
Strassmann, G, Sturner, W, Helpern, M (1969). Brain lesions, especially lenticular nucleus softening in heroin addicts, barbiturate poisoning, late death after hanging and heart arrest during anesthesia. Beitrëge zur gerichtlichen Medizin 25, 236242.Google ScholarPubMed
Talairach, J, Tournoux, P (1988). Co-Planar Stereotaxic Atlas of the Human Brain. 3-Dimensional Proportional System: An Approach to Cerebral Imaging. Thieme Medical Publishers: Stuttgart and New York.Google Scholar
Tanabe, J, Tregellas, JR, Dalwani, M, Thompson, L, Owens, E, Crowley, T, Banich, M (2009). Medial orbitofrontal cortex gray matter is reduced in abstinent substance-dependent individuals. Biological Psychiatry 65, 160164.CrossRefGoogle ScholarPubMed
The Scottish Government (2010). Research for Recovery: a Review of the Drugs Evidence Base. Scottish Government Social Research (http://www.gov.scot/resource/doc/321958/0103435.pdf). Accessed November 2015.Google Scholar
Trujillo, KA (2002). The neurobiology of opioid tolerance, dependence and sensitization: mechanisms of NMDA receptor-dependent synaptic plasticity. Neurotoxicity Research 4, 373391.CrossRefGoogle ScholarPubMed
Volkow, ND, Fowler, JS (2000). Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex 10, 318325.CrossRefGoogle ScholarPubMed
Volkow, ND, Wang, GJ, Fowler, JS, Logan, J, Angrist, B, Hitzemann, R, Lieberman, J, Pappas, N (1997). Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors. American Journal of Psychiatry 154, 5055.Google ScholarPubMed
Volkow, ND, Wang, G-J, Fowler, JS, Tomasi, D, Telang, F (2011). Addiction: beyond dopamine reward circuitry. Proceedings of the National Academy of Sciences USA 108, 1503715042.CrossRefGoogle ScholarPubMed
Walker, JM, Farney, RJ, Rhondeau, SM, Boyle, KM, Valentine, K, Cloward, TV, Shilling, KC (2007). Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. Journal of Clinical Sleep Medicine 3, 455461.CrossRefGoogle ScholarPubMed
Wang, D, Teichtahl, H (2007). Opioids, sleep architecture and sleep-disordered breathing. Sleep Medicine Reviews 11, 3546.CrossRefGoogle ScholarPubMed
Wang, D, Teichtahl, H, Drummer, O, Goodman, C, Cherry, G, Cunnington, D, Kronborg, I (2005). Central sleep apnea in stable methadone maintenance treatment patients. Chest 128, 13481356.CrossRefGoogle ScholarPubMed
Wang, Y, Li, W, Li, Q, Yang, W, Zhu, J, Wang, W (2011). White matter impairment in heroin addicts undergoing methadone maintenance treatment and prolonged abstinence: a preliminary DTI study. Neuroscience Letters 494, 4953.CrossRefGoogle ScholarPubMed
Williams, TM, Daglish, MR, Lingford-Hughes, A, Taylor, LG, Hammers, A, Brooks, DJ, Grasby, P, Myles, JS, Nutt, DJ (2007). Brain opioid receptor binding in early abstinence from opioid dependence: positron emission tomography study. British Journal of Psychiatry 191, 6369.CrossRefGoogle ScholarPubMed
Woerner, C, Overstreet, K (1999). Wechsler Abbreviated Scale of Intelligence (WASI). Psychological Corp.: San Antonio, TX.Google Scholar
Yuan, Y, Zhu, Z, Shi, J, Zou, Z, Yuan, F, Liu, Y, Lee, TM, Weng, X (2009). Gray matter density negatively correlates with duration of heroin use in young lifetime heroin-dependent individuals. Brain Cognition 71, 223228.CrossRefGoogle ScholarPubMed