Abstract
Rationale
Non-medical prescription opioid use (NMPOU) has become a major public health issue in the USA and is also increasing in Europe. However, little is known about neuropsychological associations of NMPOU—specifically regarding social cognition, which is essential for social functioning and treatability of opioid dependence. Previous studies with heroin users and opioid-substituted patients reported deficits in various cognitive functions, but these results are likely confounded by comorbid physical and psychiatric diseases, overdose-associated hypoxia, and adulteration of street heroin. Therefore, the purpose of the present study was to investigate social and non-social cognition in a relatively pure NMPOU sample taking opioid analgesics or antitussives.
Methods
We assessed 23 individuals with NMPOU objectively confirmed by hair analyses and 29 opioid-naïve, healthy controls, employing a comprehensive neuropsychological test battery.
Results
Significant impairments were found between NMPOU individuals and controls regarding the cognitive domains of attention (p < .01, Hedge’s g = .85), declarative memory (p < .05, g = .66), and global cognitive empathy (p < .01, g = 0.99)—the latter included problems with emotion recognition from faces, voices, and complex scenes. Opioid hair concentrations transformed to morphine equivalents were negatively correlated with global cognitive empathy (r = − 0.52, p < .01), suggesting dose-dependent deficits.
Conclusion
In contrast to stimulant users primarily displaying deficits in emotional empathy, opioid users showed relatively selective impairments in measures of cognitive empathy, with dose-dependent effects suggesting potential opioid-induced deficits and involvement of the opioid-system in processes of cognitive empathy. These results have important implications for future interventions of opioid dependence targeting social functioning and consequently enhancing therapy outcome and preventing relapse.
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References
Baiamonte BA, Lee FA, Gould HJ 3rd, Soignier RD (2013) Morphine-induced cognitive impairment is attenuated by induced pain in rats. Behav Neurosci 127:524–534. https://doi.org/10.1037/a0033027
Baldacchino A, Balfour DJ, Passetti F, Humphris G, Matthews K (2012) Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis. Neurosci Biobehav Rev 36:2056–2068. https://doi.org/10.1016/j.neubiorev.2012.06.006
Baumgartner U et al (2006) High opiate receptor binding potential in the human lateral pain system. Neuroimage 30:692–699. https://doi.org/10.1016/j.neuroimage.2005.10.033
Beadle JN, Sheehan AH, Dahlben B, Gutchess AH (2015) Aging, empathy, and prosociality. J Gerontol B Psychol Sci Soc Sci 70:215–224. https://doi.org/10.1093/geronb/gbt091
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571
Bernhardt BC, Singer T (2012) The neural basis of empathy. Annu Rev Neurosci 35:1–23. https://doi.org/10.1146/annurev-neuro-062111-150536
Bertoux M, O'Callaghan C, Dubois B, Hornberger M (2016) In two minds: executive functioning versus theory of mind in behavioural variant frontotemporal dementia. J Neurol Neurosurg Psychiatry 87:231–234. https://doi.org/10.1136/jnnp-2015-311643
Blair RJ (2005) Responding to the emotions of others: dissociating forms of empathy through the study of typical and psychiatric populations. Conscious Cogn 14:698–718. https://doi.org/10.1016/j.concog.2005.06.004
Broseus J, Gentile N, Esseiva P (2016) The cutting of cocaine and heroin: a critical review. Forensic Sci Int 262:73–83. https://doi.org/10.1016/j.forsciint.2016.02.033
Byrd DA et al (2013) Isolating cognitive and neurologic HIV effects in substance-dependent, confounded cohorts: a pilot study. J Int Neuropsychol Soc 19:463–473. https://doi.org/10.1017/S1355617712001634
Cohen J (1988) Statistical power analysis for the bevavioral sciences, 2nd edn. Lawrence Erlbaum Associates, Hillsday, New Jersey
Cooper GA, Kronstrand R, Kintz P, Society of Hair T (2012) Society of Hair Testing guidelines for drug testing in hair. Forensic Sci Int 218:20–24. https://doi.org/10.1016/j.forsciint.2011.10.024
Craparo G, Gori A, Dell’Aera S, Costanzo G, Fasciano S, Tomasello A, Vicario CM (2016) Impaired emotion recognition is linked to alexithymia in heroin addicts. PeerJ 4:e1864. https://doi.org/10.7717/peerj.1864
Cusi AM, Macqueen GM, Spreng RN, McKinnon MC (2011) Altered empathic responding in major depressive disorder: relation to symptom severity, illness burden, and psychosocial outcome. Psychiatry Res 188:231–236. https://doi.org/10.1016/j.psychres.2011.04.013
Darke S (2011) The life of the heroin user, typical beginnings, trajectories and outcomes. Cambridge University Press, Cambridge
Darke S, Sims J, McDonald S, Wickes W (2000) Cognitive impairment among methadone maintenance patients. Addiction 95:687–695
Davis MH (1983) Measuring individual-differences in empathy - evidence for a multidimensional approach. J Pers Soc Psychol 44:113–126. https://doi.org/10.1037/0022-3514.44.1.113
Decety J, Jackson PL (2004) The functional architecture of human empathy. Behav Cogn Neurosci Rev 3:71–100. https://doi.org/10.1177/1534582304267187
Derntl B, Finkelmeyer A, Toygar TK, Hulsmann A, Schneider F, Falkenberg DI, Habel U (2009) Generalized deficit in all core components of empathy in schizophrenia. Schizophr Res 108:197–206. https://doi.org/10.1016/j.schres.2008.11.009
Dziobek I et al (2006) Introducing MASC: a movie for the assessment of social cognition. J Autism Dev Disord 36:623–636. https://doi.org/10.1007/s10803-006-0107-0
Dziobek I, Rogers K, Fleck S, Bahnemann M, Heekeren HR, Wolf OT, Convit A (2008) Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the multifaceted empathy test (MET). J Autism Dev Disord 38:464–473. https://doi.org/10.1007/s10803-007-0486-x
Dziobek I, Preissler S, Grozdanovic Z, Heuser I, Heekeren HR, Roepke S (2011) Neuronal correlates of altered empathy and social cognition in borderline personality disorder. Neuroimage 57:539–548. https://doi.org/10.1016/j.neuroimage.2011.05.005
EMCDDA (2017) European drug report 2017: trends and developments. Publications Office of the European Union, Luxembourg
Ersche KD, Clark L, London M, Robbins TW, Sahakian BJ (2006) Profile of executive and memory function associated with amphetamine and opiate dependence. Neuropsychopharmacology 31:1036–1047. https://doi.org/10.1038/sj.npp.1300889
Fan Y, Duncan NW, de Greck M, Northoff G (2011) Is there a core neural network in empathy? An fMRI based quantitative meta-analysis. Neurosci Biobehav Rev 35:903–911. https://doi.org/10.1016/j.neubiorev.2010.10.009
Fareed A, Kim J, Ketchen B, Kwak WJ, Wang D, Shongo-Hiango H, Drexler K (2017) Effect of heroin use on changes of brain functions as measured by functional magnetic resonance imaging, a systematic review. J Addict Dis 36:105–116. https://doi.org/10.1080/10550887.2017.1280898
Furnham A, Henderson M (1982) The good, the bad and the mad - response bias in self-report measures. Pers Indiv Differ 3:311–320. https://doi.org/10.1016/0191-8869(82)90051-4
Garland EL, Froeliger B, Zeidan F, Partin K, Howard MO (2013) The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways. Neurosci Biobehav Rev 37:2597–2607. https://doi.org/10.1016/j.neubiorev.2013.08.006
Guttman H, Laporte L (2002) Alexithymia, empathy, and psychological symptoms in a family context. Compr Psychiatry 43:448–455. https://doi.org/10.1053/comp.2002.35905
Han B, Compton WM, Blanco C, Crane E, Lee J, Jones CM (2017) Prescription opioid use, misuse, and use disorders in U.S. adults: 2015 National Survey on drug use and health. Ann Intern Med 167:293–301. https://doi.org/10.7326/M17-0865
Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD (1987) Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse 13:293–308. https://doi.org/10.3109/00952998709001515
Harada CN, Natelson Love MC, Triebel KL (2013) Normal cognitive aging. Clin Geriatr Med 29:737–752. https://doi.org/10.1016/j.cger.2013.07.002
Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom tolerance questionnaire. Br J Addict 86:1119–1127
Hedges LV, Olkin I (1985) Statistical methods for meta-analysis. Academic Press, New York
Helmstaedter C, Lendt M, Lux S (2001) VLMT. Verbaler Lern- und Merkfähigkeitstest (Verbal learning and memory test). Beltz, Göttingen
Hulka LM, Preller KH, Vonmoos M, Broicher SD, Quednow BB (2013) Cocaine users manifest impaired prosodic and cross-modal emotion processing. Front Psychiatry 4:98
Hynes CA, Baird AA, Grafton ST (2006) Differential role of the orbital frontal lobe in emotional versus cognitive perspective-taking. Neuropsychologia 44:374–383. https://doi.org/10.1016/j.neuropsychologia.2005.06.011
Kendall SE, Sjøgren P, Pimenta CAM, Højsted J, Kurita GP (2010) The cognitive effects of opioids in chronic non-cancer pain. PAIN 150:225–230. https://doi.org/10.1016/j.pain.2010.05.012
Kornreich C et al (2003) Impaired emotional facial expression recognition in alcoholics, opiate dependence subjects, methadone maintained subjects and mixed alcohol-opiate antecedents subjects compared with normal controls. Psychiatry Res 119:251–260
Kret ME, De Gelder B (2012) A review on sex differences in processing emotional signals. Neuropsychologia 50:1211–1221. https://doi.org/10.1016/j.neuropsychologia.2011.12.022
Laux L, Glanzmann P, Schaffner P, Spielberger CD (1981) State-Trait-Angstinventar
Lehrl S (1999) Mehrfachwahl-Wortschatz-Intelligenztest (MWT-B), 4th edn. Hogrefe, Göttingen
Lugoboni F et al (2017) Co-occurring attention deficit hyperactivity disorder symptoms in adults affected by heroin dependence: patients characteristics and treatment needs. Psychiatry Res 250:210–216. https://doi.org/10.1016/j.psychres.2017.01.052
Lutz PE, Kieffer BL (2013) The multiple facets of opioid receptor function: implications for addiction. Curr Opin Neurobiol 23:473–479. https://doi.org/10.1016/j.conb.2013.02.005
Machin AJ, Dunbar RIM (2011) The brain opioid theory of social attachment: a review of the evidence. Behaviour 148:985–1025. https://doi.org/10.1163/000579511x596624
Massey SH, Newmark RL, Wakschlag LS (2017) Explicating the role of empathic processes in substance use disorders: a conceptual framework and research agenda. Drug Alcohol Rev. https://doi.org/10.1111/dar.12548
Mazza M et al (2015) Neural activity related to cognitive and emotional empathy in post-traumatic stress disorder. Behav Brain Res 282:37–45. https://doi.org/10.1016/j.bbr.2014.12.049
McCauley JL, Killeen T, Gros DF, Brady KT, Back SE (2012) Posttraumatic stress disorder and co-occurring substance use disorders: advances in assessment and treatment. Clin Psychol-Sci Pr 19:283–304. https://doi.org/10.1111/cpsp.12006
McDonald S, Darke S, Kaye S, Torok M (2013) Deficits in social perception in opioid maintenance patients, abstinent opioid users and non-opioid users. Addiction 108:566–574. https://doi.org/10.1111/add.12040
Miller PA, Bernzweig J, Eisenberg N, Fabes RA (1991) The development and socialization of prosocial behavior. In: Hinde RA, Groebel J (eds) Cooperation and Prosocial behaviour. Cambridge University Press, Cambridge
Mintzer MZ, Johnson MW (2007) Opioids. In: Kalechstein A, van Gorp WG (eds) Neuropsychology and substance use. Taylor & Francis, New York and London
Moriarty O, McGuire BE, Finn DP (2011) The effect of pain on cognitive function: a review of clinical and preclinical research. Prog Neurobiol 93:385–404. https://doi.org/10.1016/j.pneurobio.2011.01.002
Mounteney J, Giraudon I, Denissov G, Griffiths P (2015) Fentanyls: are we missing the signs? Highly potent and on the rise in Europe. Int J Drug Policy. https://doi.org/10.1016/j.drugpo.2015.04.003
Nummenmaa L, Tuominen L (2017) Opioid system and human emotions. Br J Pharmacol. https://doi.org/10.1111/bph.13812
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 23:113–126. https://doi.org/10.1016/s0893-133x(00)00097-x
Peckham AD, McHugh RK, Otto MW (2010) A meta-analysis of the magnitude of biased attention in depression. Depress Anxiety 27:1135–1142. https://doi.org/10.1002/da.20755
Pfabigan DM, Seidel EM, Wucherer AM, Keckeis K, Derntl B, Lamm C (2015) Affective empathy differs in male violent offenders with high- and low-trait psychopathy. J Personal Disord 29:42–61. https://doi.org/10.1521/pedi_2014_28_145
Preller KH et al (2014) Impaired emotional empathy and related social network deficits in cocaine users. Addict Biol 19:452–466. https://doi.org/10.1111/adb.12070
Prosser J, London ED, Galynker II (2009) Sustained attention in patients receiving and abstinent following methadone maintenance treatment for opiate dependence: performance and neuroimaging results. Drug Alcohol Depend 104:228–240. https://doi.org/10.1016/j.drugalcdep.2009.04.022
Quednow BB (2017) Social cognition and interaction in stimulant use disorders. Curr Opin Behav Sci 13:55–62. https://doi.org/10.1016/j.cobeha.2016.10.001
Quednow BB, Kuhn KU, Hoenig K, Maier W, Wagner M (2004) Prepulse inhibition and habituation of acoustic startle response in male MDMA ('ecstasy') users, cannabis users, and healthy controls. Neuropsychopharmacology 29:982–990. https://doi.org/10.1038/sj.npp.1300396
Rapeli P, Fabritius C, Kalska H, Alho H (2011) Cognitive functioning in opioid-dependent patients treated with buprenorphine, methadone, and other psychoactive medications: stability and correlates. BMC Clin Pharmacol 11:13. https://doi.org/10.1186/1472-6904-11-13
Rösler M et al (2005) Instrumente zur Diagnostik der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Erwachsenenalter. Nervenarzt 76:129–130. https://doi.org/10.1007/s00115-004-1848-7
Saedi E, Gheini MR, Faiz F, Arami MA (2016) Diabetes mellitus and cognitive impairments. World J Diabetes 7:412–422. https://doi.org/10.4239/wjd.v7.i17.412
Schaffer SG, Gregory A, Froming KB, Levy CM, Ekman P (2006) In: emotion processing: the comprehensive affect testing system User's manual. Psychology Software, Inc., Sanford
Schaffer SG, Wisniewski A, Dahdah M, Froming KB (2009) The comprehensive affect testing system-abbreviated: effects of age on performance. Arch Clin Neuropsychol 24:89–104. https://doi.org/10.1093/arclin/acp012
Schmidt P, Haberthur A, Soyka M (2017) Cognitive functioning in formerly opioid-dependent adults after at least 1 year of abstinence: a naturalistic study. Eur Addict Res 23:269–275. https://doi.org/10.1159/000485032
Singer T, Lamm C (2009) The social neuroscience of empathy. Ann N Y Acad Sci 1156:81–96. https://doi.org/10.1111/j.1749-6632.2009.04418.x
Soyka M et al (2008) Cognitive functioning during methadone and buprenorphine treatment: results of a randomized clinical trial. J Clin Psychopharmacol 28:699–703. https://doi.org/10.1097/JCP.0b013e31818a6d38
Stange K, Kruger M, Janke E, Lichtinghagen R, Bleich S, Hillemacher T, Heberlein A (2017) Positive association of personal distress with testosterone in opiate-addicted patients. J Addict Dis 36:167–174. https://doi.org/10.1080/10550887.2017.1303980
Tomei A, Besson J, Reber N, Rougemont-Bucking A, Grivel J (2017) Personal distress and empathic concern in methadone-maintained patients. J Subst Use 22:37–41. https://doi.org/10.3109/14659891.2016.1140238
UNODC (2017) World drug report 2017. United Nations publication, United Nations
Upadhyay J et al (2010) Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. Brain 133:2098–2114. https://doi.org/10.1093/brain/awq138
van Holst RJ, Schilt T (2011) Drug-related decrease in neuropsychological functions of abstinent drug users. Curr Drug Abuse Rev 4:42–56
Vonmoos M et al (2013) Cognitive dysfunctions in recreational and dependent cocaine users: role of attention-deficit hyperactivity disorder, craving and early age at onset. Br J Psychiatry 203:35–43. https://doi.org/10.1192/bjp.bp.112.118091
Walter H (2012) Social cognitive neuroscience of empathy: concepts, circuits, and genes. Emot Rev 4:9–17. https://doi.org/10.1177/1754073911421379
Wechsler D (1997) Wechsler Memory Scale. Manual, 3rd edn., San Antonio
Wittchen HU, Wunderliche U, Gruschwitz S, Zaudig M (1997) SKID-I. Strukturiertes Klinisches Interview für DSM-IV Achse I: Psychische Störungen (SCID-I. Structured Clinical Interview for DSM-IV Axes I: Mental Disorders). Hogrefe, Göttingen
Wunderli MD et al (2017) Social cognition and interaction in chronic users of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Int J Neuropsychopharmacol. https://doi.org/10.1093/ijnp/pyx098
Yarlott L, Heald E, Forton D (2017) Hepatitis C virus infection, and neurological and psychiatric disorders - a review. J Adv Res 8:139–148. https://doi.org/10.1016/j.jare.2016.09.005
Younger JW, Chu LF, D’Arcy NT, Trott KE, Jastrzab LE, Mackey SC (2011) Prescription opioid analgesics rapidly change the human brain. Pain 152:1803–1810. https://doi.org/10.1016/j.pain.2011.03.028
Acknowledgments
We are grateful to Matthias Humm (Drug Information Centre, DIZ, and www.saferparty.ch), Markus Herdener (University Hospital for Psychiatry Zurich and Centre for Use Disorders, ZAE), and Andreas Wahl-Kordon (Oberbergklinik Schwarzwald) for supporting the recruitment. Furthermore, we thank Jael Bernath, Martina Thoma, and Kateryna Mudrak for their excellent support with the assessment of the participants. We are also grateful to Dr. David Cole for the proof-reading of our manuscript.
Funding
The study was funded by the Herzog-Egli Foundation and starting grants of the Medical Faculty of the University of Zurich and of the Psychiatric Hospital of the University of Zurich to BBQ. SLK was financed by a grant of the Swiss National Science Foundation (105319_162639/1) to BBQ.
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SLK and BBQ designed the study. MS supported the recruitment and the implementation of the study. SLK, EN, and FB conducted the assessments. MRB conducted the hair analyses. SLK conducted the statistical analyses. SLK and BBQ wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
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The study was approved by the Cantonal Ethics Committee of Zurich. All participants provided written informed consent and received compensation for their participation.
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The authors declare that there is no conflict of interest.
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Kroll, S.L., Nikolic, E., Bieri, F. et al. Cognitive and socio-cognitive functioning of chronic non-medical prescription opioid users. Psychopharmacology 235, 3451–3464 (2018). https://doi.org/10.1007/s00213-018-5060-z
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DOI: https://doi.org/10.1007/s00213-018-5060-z