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Traits and Biomarkers for Addiction Risk in Schizophrenia

  • Dual Diagnosis (A Chambers, Section Editor)
  • Published:
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Abstract

Purpose

The most common addictions in schizophrenia include tobacco, cannabis, alcohol, stimulants/recreational drugs, and gambling. This review discusses the multifactorial risk factors for addictions in people with schizophrenia.

Findings

Several hypotheses have been proposed to explain addiction comorbidity in schizophrenia, and potential biomarkers conferring addiction risk in patients have been identified (e.g., catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), v-akt murine thymoma viral oncogene homolog 1 (AKT1), cortical inhibition, working memory). Neurotransmitter systems including dopaminergic, glutamatergic, and GABAergic pathways are associated with the pathophysiology of both schizophrenia and addictions.

Summary

Developing effective treatments for schizophrenia and comorbid addictions is warranted and should involve further studies of neurobiological underpinnings of addiction risk in schizophrenia.

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References

Papers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

  1. Volkow ND. Substance use disorders in schizophrenia—clinical implications of comorbidity. Schizophr Bull. 2009;35(3):469–72.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wilson N, Cadet JL. Comorbid mood, psychosis, and marijuana abuse disorders: a theoretical review. J Addict Dis. 2009;28(4):309–19.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Picciotto MR, Caldarone BJ, King SL, Zachariou V. Nicotinic receptors in the brain. Links between molecular biology and behavior. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2000;22(5):451–65.

    Article  CAS  Google Scholar 

  4. Williams JM, Ziedonis DM, Abanyie F, Steinberg ML, Foulds J, Benowitz NL. Increased nicotine and cotinine levels in smokers with schizophrenia and schizoaffective disorder is not a metabolic effect. Schizophr Res. 2005;79(2–3):323–35.

    Article  PubMed  Google Scholar 

  5. Smith PH, Mazure CM, McKee SA. Smoking and mental illness in the U.S. population. Tob Control. 2014;23(e2):e147–53.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014;311(2):145–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: a population-based prevalence study. JAMA. 2000;284(20):2606–10.

    Article  CAS  PubMed  Google Scholar 

  8. de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res. 2005;76(2–3):135–57.

    Article  PubMed  Google Scholar 

  9. de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry. 1995;152(3):453–5.

    Article  PubMed  Google Scholar 

  10. Steinberg ML, Ziedonis DM, Krejci JA, Brandon TH. Motivational interviewing with personalized feedback: a brief intervention for motivating smokers with schizophrenia to seek treatment for tobacco dependence. J Consult Clin Psychol. 2004;72(4):723–8.

    Article  PubMed  Google Scholar 

  11. McClave AK, McKnight-Eily LR, Davis SP, Dube SR. Smoking characteristics of adults with selected lifetime mental illnesses: results from the 2007 National Health Interview Survey. Am J Public Health. 2010;100(12):2464–72.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Williams JM, Gandhi KK, Lu SE, Kumar S, Steinberg ML, Cottler B, Benowitz NL. Shorter interpuff interval is associated with higher nicotine intake in smokers with schizophrenia. Drug Alcohol Depend. 2011;118(2–3):313–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Williams JM, Gandhi KK, Lu SE, Kumar S, Shen J, Foulds J, Kipen H, Benowitz NL. Higher nicotine levels in schizophrenia compared with controls after smoking a single cigarette. Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco. 2010;12(8):855–9.

    Article  CAS  Google Scholar 

  14. • Tidey JW, Rohsenow DJ, Kaplan GB, Swift RM. Cigarette smoking topography in smokers with schizophrenia and matched non-psychiatric controls. Drug Alcohol Depend. 2005;80(2):259–65. This is an important tobacco smoking topography study demonstrating differential smoking behaviors in smokers with schizophrenia compared to non-psychiatric smokers. Results suggest that patients smoke more intensely and obtain more reinforcement from smoking than matched non-psychiatric smoking controls.

    Article  PubMed  Google Scholar 

  15. Tidey JW, Colby SM, Xavier EM. Effects of smoking abstinence on cigarette craving, nicotine withdrawal, and nicotine reinforcement in smokers with and without schizophrenia. Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco. 2014;16(3):326–34.

    Article  CAS  Google Scholar 

  16. •• Wing VC, Wass CE, Soh DW, George TP. A review of neurobiological vulnerability factors and treatment implications for comorbid tobacco dependence in schizophrenia. Ann N Y Acad Sci. 2012;1248:89–106. This is an important review that proposes unique risk factors that may result in initiation and maintenance of co-morbid nicotine dependence in schizophrenia. Additionally, it suggests potential treatment options via an understanding of the neurobiological dysfunctions found in patients relating to nAChRs and neurotransmitters.

    Article  CAS  PubMed  Google Scholar 

  17. •• Breese CR, Lee MJ, Adams CE, et al. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2000;23(4):351–64. This post-mortem study suggested the abnormal expression of nAChR in smokers with schizophrenia compared to controls. Additionally, decreased nAChRs were found in specific regions of the brain, including the cortex, hippocampus and caudate.

    Article  CAS  Google Scholar 

  18. •• D’Souza DC, Esterlis I, Carbuto M, et al. Lower ss2*-nicotinic acetylcholine receptor availability in smokers with schizophrenia. Am J Psychiatry. 2012;169(3):326–34. This post-mortem study showed that patients with schizophrenia have reduced nAChR across brain regions. Importantly these brain regions are involved in the mediation of cognition and thus may represent not only a target for pharmacotherapy treatment for smoking cessation, but also for cognitive deficits in schizophrenia.

    Article  PubMed  Google Scholar 

  19. • Morisano D, Wing VC, Sacco KA, Arenovich T, George TP. Effects of tobacco smoking on neuropsychological function in schizophrenia in comparison to other psychiatric disorders and non-psychiatric controls. The American journal on addictions/American Academy of Psychiatrists in Alcoholism and Addictions. 2013;22(1):46–53. This study demonstrated that schizophrenia subjects performed significantly worse than controls across several cognitive domains, whereas other mental health disorders such as bipolar and major depressive disorder subjects did not differ from controls. Further, smoking was also associated with cognitive improvements only in schizophrenia smokers.

    Article  Google Scholar 

  20. Smith RC, Singh A, Infante M, Khandat A, Kloos A. Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2002;27(3):479–97.

    Article  CAS  Google Scholar 

  21. • Sacco KA, Termine A, Seyal A, et al. Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry. 2005;62(6):649–59. This study demonstrated that deficits in spatial working memory as a result of smoking abstinence was selective to smokers with schizophrenia and not controls. The authors also showed that smoking reinstatment enhanced working memory and sustained attention in patients and was blocked by the antagonist mecamylamine.

    Article  PubMed  Google Scholar 

  22. • Wing VC, Wass CE, Bacher I, Rabin RA, George TP. Varenicline modulates spatial working memory deficits in smokers with schizophrenia. Schizophr Res. 2013;149(1–3):190–1. This three-day paradigm study, demonstrated that in the placebo group there was a worsening of working memory performance with abstinence, which was reversed with smoking reinstatement, whereas the 1 mg dose of varenicline was able to block this effect. This work further showed that this effect of varenicline was selective for patients with schizophrenia as no effect was found in controls.

    Article  PubMed  Google Scholar 

  23. •• George TP, Vessicchio JC, Termine A, Sahady DM, Head CA, Pepper WT, Kosten TR, Wexler BE. Effects of smoking abstinence on visuospatial working memory function in schizophrenia. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2002;26(1):75–85. This is an important study that examined the effects of acute and prolonged smoking abstinence on working memory in schizoprhenia and control smokers. Results suggested smoking differentially alters working memory and may have beneficial effects in schizophrenia smokers and not controls.

    Article  Google Scholar 

  24. Koskinen J, Lohonen J, Koponen H, Isohanni M, Miettunen J. Prevalence of alcohol use disorders in schizophrenia—a systematic review and meta-analysis. Acta Psychiatr Scand. 2009;120(2):85–96.

    Article  CAS  PubMed  Google Scholar 

  25. Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264(19):2511–8.

    Article  CAS  PubMed  Google Scholar 

  26. Morrow AL, Montpied P, Lingford-Hughes A, Paul SM. Chronic ethanol and pentobarbital administration in the rat: effects on GABAA receptor function and expression in brain. Alcohol. 1990;7(3):237–44.

    Article  CAS  PubMed  Google Scholar 

  27. Manning V, Betteridge S, Wanigaratne S, Best D, Strang J, Gossop M. Cognitive impairment in dual diagnosis inpatients with schizophrenia and alcohol use disorder. Schizophr Res. 2009;114(1–3):98–104.

    Article  PubMed  Google Scholar 

  28. Soni SD, Brownlee M. Alcohol abuse in chronic schizophrenics: implications for management in the community. Acta Psychiatr Scand. 1991;84(3):272–6.

    Article  CAS  PubMed  Google Scholar 

  29. Jones RM, Lichtenstein P, Grann M, Langstrom N, Fazel S. Alcohol use disorders in schizophrenia: a national cohort study of 12,653 patients. The Journal of clinical psychiatry. 2011;72(6):775–9. quiz 878-779

    Article  PubMed  Google Scholar 

  30. Kumar CN, Thirthalli J, Suresha KK, Arunachala U, Gangadhar BN. Alcohol use disorders in patients with schizophrenia: comparative study with general population controls. Addict Behav. 2015;45:22–5.

    Article  PubMed  Google Scholar 

  31. Maxwell S, Shinderman MS. Use of naltrexone in the treatment of alcohol use disorders in patients with concomitant major mental illness. J Addict Dis. 2000;19(3):61–9.

    Article  CAS  PubMed  Google Scholar 

  32. Drake RE, Mueser KT. Co-occurring alcohol use disorder and schizophrenia. Alcohol Res Health 2002;26(2).

  33. Mishra BR, Nizamie SH, Das B, Praharaj SK. Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study. Addiction. 2010;105(1):49–55.

    Article  PubMed  Google Scholar 

  34. Koskinen J, Lohonen J, Koponen H, Isohanni M, Miettunen J. Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis. Schizophr Bull. 2010;36(6):1115–30.

    Article  PubMed  Google Scholar 

  35. UNODC. World drug report 2015. New York: United Nations Office on Drugs and Crime; 2015.

    Book  Google Scholar 

  36. Wisdom JP, Manuel JI, Drake RE. Substance use disorder among people with first-episode psychosis: a systematic review of course and treatment. Psychiatr Serv. 2011;62(9):1007–12.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Green B, Young R, Kavanagh D. Cannabis use and misuse prevalence among people with psychosis. The British journal of psychiatry: the journal of mental science. 2005;187:306–13.

    Article  Google Scholar 

  38. Arendt M, Rosenberg R, Fjordback L, Brandholdt J, Foldager L, Sher L, Munk-Jorgensen P. Testing the self-medication hypothesis of depression and aggression in cannabis-dependent subjects. Psychol Med. 2007;37(7):935–45.

    Article  PubMed  Google Scholar 

  39. Manrique-Garcia E, Zammit S, Dalman C, Hemmingsson T, Andreasson S, Allebeck P. Prognosis of schizophrenia in persons with and without a history of cannabis use. Psychol Med. 2014;44(12):2513–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Leweke FM, Gerth CW, Klosterkotter J. Cannabis-associated psychosis: current status of research. CNS Drugs. 2004;18(13):895–910.

    Article  PubMed  Google Scholar 

  41. • Caspi A, Moffitt TE, Cannon M, et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005;57(10):1117–27. This longitudinal study examined the effects of a functional polymorphism in the COMT gene on cannabis use in the development of early psychosis. The authors provided evidence of a gene by environmental interaction suggesting susceptibility of certain genetic risk factors to influence vulnerability to addiction risk and schizophrenia.

    Article  CAS  PubMed  Google Scholar 

  42. Piomelli D. The element of surprise. Nat Med. 2008;14(7):720–1.

    Article  CAS  PubMed  Google Scholar 

  43. Rabin RA, Zakzanis KK, Daskalakis ZJ, George TP. Effects of cannabis use status on cognitive function, in males with schizophrenia. Psychiatry Res. 2013;206(2–3):158–65.

    Article  CAS  PubMed  Google Scholar 

  44. •• D'Souza DC, Abi-Saab WM, Madonick S, et al. Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry. 2005;57(6):594–608. This double-blind, placebo-controlled study examined behavioral, cognitive, mtoor and endocrine effects of THC in schizoprhenia patients. Results showed exacerbation of core psychotic featurs and cognitive deficits in patients and overall differential effects compared to controls.

    Article  PubMed  CAS  Google Scholar 

  45. •• Rabin RA, Zakzanis KK, George TP. The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis. Schizophr Res. 2011;128(1–3):111–6. This meta-analysis examined evidence for the effects of cannabis use on cognitive function in schizophrenia without other co-morbid substance use disorders. Results suggest minimal effects of cannabis use on cognitive function, but given that all studies reviewed were cross-sectional discusses the need for longitudinal evaluation of cannabis effects on cognition in schizophrenia.

    Article  PubMed  Google Scholar 

  46. Yucel M, Bora E, Lubman DI, et al. The impact of cannabis use on cognitive functioning in patients with schizophrenia: a meta-analysis of existing findings and new data in a first-episode sample. Schizophr Bull. 2012;38(2):316–30.

    Article  PubMed  Google Scholar 

  47. Budney AJ, Moore BA, Rocha HL, Higgins ST. Clinical trial of abstinence-based vouchers and cognitive-behavioral therapy for cannabis dependence. J Consult Clin Psychol. 2006;74(2):307–16.

    Article  PubMed  Google Scholar 

  48. Sigmon SC, Higgins ST. Voucher-based contingent reinforcement of marijuana abstinence among individuals with serious mental illness. J Subst Abus Treat. 2006;30(4):291–5.

    Article  Google Scholar 

  49. Sara GE, Burgess PM, Malhi GS, Whiteford HA, Hall WC. Stimulant and other substance use disorders in schizophrenia: prevalence, correlates and impacts in a population sample. The Australian and New Zealand journal of psychiatry. 2014;48(11):1036–47.

    Article  PubMed  Google Scholar 

  50. Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T. The need for speed: an update on methamphetamine addiction. Journal of psychiatry & neuroscience: JPN. 2006;31(5):301–13.

    Google Scholar 

  51. Thoma P, Daum I. Comorbid substance use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings. Psychiatry Clin Neurosci. 2013;67(6):367–83.

    Article  PubMed  Google Scholar 

  52. McKetin R, Lubman DI, Baker AL, Dawe S, Ali RL. Dose-related psychotic symptoms in chronic methamphetamine users: evidence from a prospective longitudinal study. JAMA Psychiatry. 2013;70(3):319–24.

    Article  PubMed  Google Scholar 

  53. Wobrock T, Soyka M. Pharmacotherapy of schizophrenia with comorbid substance use disorder—reviewing the evidence and clinical recommendations. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32(6):1375–85.

    Article  CAS  Google Scholar 

  54. Roll JM, Petry NM, Stitzer ML, et al. Contingency management for the treatment of methamphetamine use disorders. Am J Psychiatry. 2006;163(11):1993–9.

    Article  PubMed  Google Scholar 

  55. Shaffer HJ, Hall MN. Updating and refining prevalence estimates of disordered gambling behaviour in the United States and Canada. Can J Public Health. 2001;92(3):168–72.

    CAS  PubMed  Google Scholar 

  56. •• Desai RA, Potenza MN. A cross-sectional study of problem and pathological gambling in patients with schizophrenia/schizoaffective disorder. The Journal of clinical psychiatry. 2009;70(9):1250–7. This outpatient study sought out to determine the prevalence of co-occurrence of problem gambling behaviors in schizophrenia patients. Results suggested signficant correlates of several pathological and problem measures with clinical outcomes and stress the importance of improved preventative treatments.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Cunningham-Williams RM, Cottler LB, Compton 3rd WM, Spitznagel EL. Taking chances: problem gamblers and mental health disorders—results from the St. Louis Epidemiologic Catchment Area Study. Am J Public Health. 1998;88(7):1093–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Haydock M, Cowlishaw S, Harvey C, Castle D. Prevalence and correlates of problem gambling in people with psychotic disorders. Compr Psychiatry. 2015;58:122–9.

    Article  PubMed  Google Scholar 

  59. Chau DT, Roth RM, Green AI. The neural circuitry of reward and its relevance to psychiatric disorders. Curr Psychiatry Rep. 2004;6(5):391–9.

    Article  PubMed  Google Scholar 

  60. Potenza MN. Review. The neurobiology of pathological gambling and drug addiction: an overview and new findings. Philos Trans R Soc Lond Ser B Biol Sci. 2008;363(1507):3181–9.

    Article  Google Scholar 

  61. Dowling NA, Merkouris SS, Lorains FK. Interventions for comorbid problem gambling and psychiatric disorders: advancing a developing field of research. Addict Behav. 2016;58:21–30.

    Article  CAS  PubMed  Google Scholar 

  62. Blum K, Oscar-Berman M, Badgaiyan RD, Palomo T, Gold MS. Hypothesizing dopaminergic genetic antecedents in schizophrenia and substance seeking behavior. Med Hypotheses. 2014;82(5):606–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fernandez-Ruiz J, Gomez M, Hernandez M, de Miguel R, Ramos JA. Cannabinoids and gene expression during brain development. Neurotox Res. 2004;6(5):389–401.

    Article  PubMed  Google Scholar 

  64. Wise RA. Dopamine, learning and motivation. Nat Rev Neurosci. 2004;5(6):483–94.

    Article  CAS  PubMed  Google Scholar 

  65. Laviolette SR, Grace AA. The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction. Cell Mol Life Sci. 2006;63(14):1597–613.

    Article  CAS  PubMed  Google Scholar 

  66. Hogg RC, Raggenbass M, Bertrand D. Nicotinic acetylcholine receptors: from structure to brain function. Rev Physiol Biochem Pharmacol. 2003;147:1–46.

    CAS  PubMed  Google Scholar 

  67. Negrete JC. Clinical aspects of substance abuse in persons with schizophrenia. Can J Psychiatry. 2003;48(1):14–21.

    PubMed  Google Scholar 

  68. Grace AA. Gating of information flow within the limbic system and the pathophysiology of schizophrenia. Brain Res Brain Res Rev. 2000;31(2–3):330–41.

    Article  CAS  PubMed  Google Scholar 

  69. Pratt J, Winchester C, Dawson N, Morris B. Advancing schizophrenia drug discovery: optimizing rodent models to bridge the translational gap. Nat Rev Drug Discov. 2012;11(7):560–79.

    Article  CAS  PubMed  Google Scholar 

  70. Lewis DA, Pierri JN, Volk DW, Melchitzky DS, Woo TU. Altered GABA neurotransmission and prefrontal cortical dysfunction in schizophrenia. Biol Psychiatry. 1999;46(5):616–26.

    Article  CAS  PubMed  Google Scholar 

  71. Bridgman AC, Barr MS, Goodman MS, Chen R, Rajji TK, Daskalakis ZJ, George TP. Deficits in GABAA receptor function and working memory in non-smokers with schizophrenia. Schizophr Res. 2016;171(1–3):125–30.

    Article  PubMed  Google Scholar 

  72. Dick DM, Edenberg HJ, Xuei X, et al. Association of GABRG3 with alcohol dependence. Alcohol Clin Exp Res. 2004;28(1):4–9.

    Article  CAS  PubMed  Google Scholar 

  73. Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry. 1997;4(5):231–44.

    Article  CAS  PubMed  Google Scholar 

  74. Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985;142(11):1259–64.

    Article  CAS  PubMed  Google Scholar 

  75. Winterer G. Why do patients with schizophrenia smoke? Current opinion in psychiatry. 2010;23(2):112–9.

    Article  PubMed  Google Scholar 

  76. •• Chambers RA, Krystal JH, Self DW. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol Psychiatry. 2001;50(2):71–83. This review suggests abnormalities in frontal cortex and hippocampal formations in facilitating drug-seeking behavior via positive reinforcing effects of drug reward and reduced inhibitory control. The authors elaborate on how dysregulated dopaminergic and glutaminergic signalling in patients with schizophrenia may increase this population to addiction risk.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. •• Chambers RA, Taylor JR, Potenza MN. Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry. 2003;160(6):1041–52. This is an important review which examined adolescent neurodevelopment in brain regions associated in addiction, impulsivity and motivation. The results implicated certain developmental processes and neurocircuitry changes in frontal cortical and subcortical systems in impulse control and addiction vulnerability.

    Article  PubMed  PubMed Central  Google Scholar 

  78. • Hong LE, Thaker GK, RP MM, et al. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 2011;68(12):1195–206. This double-blind, parallel, placebo-controlled, randomized study examined effects of varenicline over short- and long-term treatment in smokers and nonsmokers with schizophrenia. Importantly, this study showed varenicline had unique procognitive effects on core schizophrenia-related biomarkers.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kendler KS, Diehl SR. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull. 1993;19(2):261–85.

    Article  CAS  PubMed  Google Scholar 

  80. Sullivan D, Pinsonneault JK, Papp AC, Zhu H, Lemeshow S, Mash DC, Sadee W. Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction. Transl Psychiatry. 2013;3:e222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Philibert RA, Gunter TD, Beach SR, Brody GH, Hollenbeck N, Andersen A, Adams W. Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa Adoption Studies. Psychiatr Genet. 2009;19(2):91–8.

    Article  PubMed  PubMed Central  Google Scholar 

  82. •• Green AI, Zimmet SV, Strous RD, Schildkraut JJ. Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine? Harv Rev Psychiatry. 1999;6(6):287–96. This is important review discusses the biological basis of substance use in relation to a "reward-deficiency syndrome" secondary to dysfunctional dopamine-mediated mesocorticolimbic systems in patients with schizophrenia. The beneficial effects of clozapine on addiction risk and schizophrenia are indicated to ameliorate deficits in brain circuitries.

    Article  CAS  PubMed  Google Scholar 

  83. George T. Neurobiological links between nicotine addiction and schizophrenia. Journal of Dual Diagnosis. 2007;3(3/4):27–42.

    Article  Google Scholar 

  84. Coyle JT. The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry. 1996;3(5):241–53.

    Article  CAS  PubMed  Google Scholar 

  85. Deng C. Effects of antipsychotic medications on appetite, weight, and insulin resistance. Endocrinol Metab Clin N Am. 2013;42(3):545–63.

    Article  Google Scholar 

  86. Kluge M, Schuld A, Himmerich H, et al. Clozapine and olanzapine are associated with food craving and binge eating: results from a randomized double-blind study. J Clin Psychopharmacol. 2007;27(6):662–6.

    Article  CAS  PubMed  Google Scholar 

  87. Mathews J, Newcomer JW, Mathews JR, Fales CL, Pierce KJ, Akers BK, Marcu I, Barch DM. Neural correlates of weight gain with olanzapine. Arch Gen Psychiatry. 2012;69(12):1226–37.

    Article  CAS  PubMed  Google Scholar 

  88. Blum K, Thanos PK, Gold MS. Dopamine and glucose, obesity, and reward deficiency syndrome. Front Psychol. 2014;5:919.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Association AP. Substance-related and addictive disorders. American Psychiatric Publishing 2013(5th Edition).

  90. Gould TJ. Addiction and cognition. Addict Sci Clin Pract. 2010;5(2):4–14.

    PubMed  PubMed Central  Google Scholar 

  91. Arndt S, Tyrrell G, Flaum M, Andreasen NC. Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment. Psychol Med. 1992;22(2):379–88.

    Article  CAS  PubMed  Google Scholar 

  92. Arseneault L, Cannon M, Witton J, Murray RM. Causal association between cannabis and psychosis: examination of the evidence. The British journal of psychiatry: the journal of mental science. 2004;184:110–7.

    Article  Google Scholar 

  93. Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 2002;325(7374):1212–3.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Kelly TM, Daley DC. Integrated treatment of substance use and psychiatric disorders. Soc Work Public Health. 2013;28(3–4):388–406.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Grella CE, Hser YI, Joshi V, Rounds-Bryant J. Drug treatment outcomes for adolescents with comorbid mental and substance use disorders. J Nerv Ment Dis. 2001;189(6):384–92.

    Article  CAS  PubMed  Google Scholar 

  96. Mangrum LF, Spence RT, Lopez M. Integrated versus parallel treatment of co-occurring psychiatric and substance use disorders. J Subst Abus Treat. 2006;30(1):79–84.

    Article  Google Scholar 

  97. Shenton ME, Whitford TJ, Kubicki M. Structural neuroimaging in schizophrenia: from methods to insights to treatments. Dialogues Clin Neurosci. 2010;12(3):317–32.

    PubMed  PubMed Central  Google Scholar 

  98. Ohi K, Hashimoto R, Yasuda Y, et al. The AKT1 gene is associated with attention and brain morphology in schizophrenia. World J Biol Psychiatry. 2013;14(2):100–13.

    Article  PubMed  Google Scholar 

  99. Xu MQ, St Clair D, Feng GY, Lin ZG, He G, Li X, He L. BDNF gene is a genetic risk factor for schizophrenia and is related to the chlorpromazine-induced extrapyramidal syndrome in the Chinese population. Pharmacogenet Genomics. 2008;18(6):449–57.

    Article  CAS  PubMed  Google Scholar 

  100. Li W, Zhou N, Yu Q, et al. Association of BDNF gene polymorphisms with schizophrenia and clinical symptoms in a Chinese population. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(6):538–45.

    Article  PubMed  CAS  Google Scholar 

  101. Hong LE, Yang X, Wonodi I, Hodgkinson CA, Goldman D, Stine OC, Stein ES, Thaker GK. A CHRNA5 allele related to nicotine addiction and schizophrenia. Genes Brain Behav. 2011;10(5):530–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Novak G, LeBlanc M, Zai C, et al. Association of polymorphisms in the BDNF, DRD1 and DRD3 genes with tobacco smoking in schizophrenia. Ann Hum Genet. 2010;74(4):291–8.

    Article  CAS  PubMed  Google Scholar 

  103. Eastwood SL, Harrison PJ. Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol Psychiatry. 2003;8(9):769. 821-731

    Article  CAS  PubMed  Google Scholar 

  104. Wedenoja J, Loukola A, Tuulio-Henriksson A, et al. Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families. Mol Psychiatry. 2008;13(7):673–84.

    Article  CAS  PubMed  Google Scholar 

  105. Nagasawa T, Kamiya T, Kawasaki Y, Higashima M, Urata K, Sakai N, Koshino Y. The relationship between auditory ERP and neuropsychological assessments in schizophrenia. Int J Psychophysiol. 1999;34(3):267–74.

    Article  CAS  PubMed  Google Scholar 

  106. Lee J, Green MF, Calkins ME, et al. Verbal working memory in schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) study: the moderating role of smoking status and antipsychotic medications. Schizophr Res. 2015;163(1–3):24–31.

    Article  PubMed  Google Scholar 

  107. Cunha PJ, Rosa PG, Ayres Ade M, et al. Cannabis use, cognition and brain structure in first-episode psychosis. Schizophr Res. 2013;147(2–3):209–15.

    Article  PubMed  Google Scholar 

  108. Wing VC, Bacher I, Wu BS, Daskalakis ZJ, George TP. High frequency repetitive transcranial magnetic stimulation reduces tobacco craving in schizophrenia. Schizophr Res. 2012;139(1–3):264–6.

    Article  PubMed  Google Scholar 

  109. Barr MS, Farzan F, Wing VC, George TP, Fitzgerald PB, Daskalakis ZJ. Repetitive transcranial magnetic stimulation and drug addiction. Int Rev Psychiatry. 2011;23(5):454–66.

    Article  PubMed  Google Scholar 

  110. Chatterjee S, Bartlett SE. Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders. CNS Neurol Disord Drug Targets. 2010;9(1):60–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. D'Souza MS, Markou A. Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments. Addict Sci Clin Pract. 2011;6(1):4–16.

    PubMed  PubMed Central  Google Scholar 

  112. • Filbey FM, McQueeny T, Kadamangudi S, Bice C, Ketcherside A. Combined effects of marijuana and nicotine on memory performance and hippocampal volume. Behav Brain Res. 2015;293:46–53. This is study examined both individual and combined effects of cannabis and tobacco on hippocampal volumes and cognitive domains. It highlights the differential abnormalities in brain-behavior relationships with use of cannabis and nicotine and underlying memory processes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Potenza MN, Sofuoglu M, Carroll KM, Rounsaville BJ. Neuroscience of behavioral and pharmacological treatments for addictions. Neuron. 2011;69(4):695–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This manuscript was support by an Institute of Medical Sciences Graduate Fellowship from the University of Toronto (to Ms. Kozak) and CIHR Operating Grant MOP#115145 (to Dr. George).

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Authors and Affiliations

  1. Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada

    Karolina Kozak, Mera S. Barr & Tony P. George

  2. Institute of Medical Sciences, University of Toronto, Toronto, Canada

    Karolina Kozak, Mera S. Barr & Tony P. George

  3. Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Mera S. Barr & Tony P. George

  4. Centre for Addiction and Mental Health, University of Toronto, 100 Stokes Street, BGB 3288, Toronto, ON, M6J 1H4, Canada

    Tony P. George

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  1. Karolina Kozak
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  2. Mera S. Barr
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  3. Tony P. George
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Correspondence to Tony P. George.

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Karolina Kozak, Dr. Mera S. Barr, and Dr. Tony P. George declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Dual Diagnosis

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Kozak, K., Barr, M.S. & George, T.P. Traits and Biomarkers for Addiction Risk in Schizophrenia. Curr Addict Rep 4, 14–24 (2017). https://doi.org/10.1007/s40429-017-0130-6

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