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Comorbidity and Trauma Study (CATS)

image - Sydney Alley 280
Date Commenced:
Expected Date of Completion:
Project Supporters:

National Institute of Drug Abuse (Grant R01 DA017305)

Drug Type:
Project Members: 
image - Briony Larance Square
Adjunct Senior Lecturer
Ph 02 9385 0333
Associate Professor
Ph 02 9385 0333
image - Gab Campbell
Research Fellow
Ph 02 9385 0286
image - Tom Santo
Post-Doctoral Research Fellow
Project Main Description: 

The Comorbidity and Trauma Study (CATS) is a large retrospective case-control study, which examined the influence of genetics and environmental factors (e.g. childhood trauma) contributing to opioid dependence liability. The present research proposes a new data linkage component, which will link data from the CATS cohort with mortality, opioid substitution therapy, emergency department and hospital data.

Project Collaborators: External: 

Professor Elliot Nelson
Department of Psychiatry, Washington University


The aim of the present research is to examine causes and predictors of mortality, and patterns of engagement with opioid substitution therapy among the CATS cohort. The specific aims of this research are to:

  • Estimate overall mortality (both underlying and contributing causes) for the CATS cohort;
  • Explore whether demographic or treatment variables are related to mortality levels during and following cessation of treatment;
  • Estimate mortality risk, according to specific causes of death;
  • Identify patterns and predictors of engagement (e.g. retention) in OST;
  • Identify patterns and predictors of emergency department presentations;
  • Identify patterns and predictors of hospital separations; and
  • Explore neonatal outcomes among opioid dependent women compared with matched controls, and associations of childbirth with engagement with OST among opioid dependent woman.
Design and Method: 

A sample of 1487 opioid dependent cases and 515 non-dependent controls matched on age, sex and socio-economic status participated in face-to-face structured interviews between 2004 and 2008. Cases were recruited from 34 of the 35 available public and private opioid substitution therapy clinics in the greater Sydney region, and through word of mouth and snowballing recruitment methods. Controls were recruited from community and employment centres, open street malls and local press servicing the same geographic area as the clinics.

Data from the CATS cohort will be linked with the following administrative databases:

  1. National Death Index (NDI) at the Australian Institute of Health and Welfare;
  2. Ministry of Health –
    • Pharmaceutical Drugs of Addiction System (PHDAS) at the Pharmaceutical Services, Legal and Regulatory Services Branch (PBS).
    • NSW Admitted Patient Data (APD) at the Health System Information and Performance Reporting Unit.
    • NSW Emergency Department Data Collection (EDDC) at the Health System Information and Performance Reporting Unit.



CATS cohort data has been linked to administrative data from the National Death Index (NDI), Pharmaceutical Drugs of Addiction System (PHDAS), NSW Admitted Patient Data (APD) and NSW Emergency Department Data Collection (EDDC) databases. Data analysis is currently underway.

  1. Maloney, E., Degenhardt, L., Darke, S., Mattick, R.P. & Nelson, E. (2007). Suicidal behaviour and associated risk factors among opioid-dependent persons: A case control study. Addiction,102, 1933-1941.
  2. Conroy, E., Degenhardt, L., Mattick, R.P. & Nelson, E. (2009). Child maltreatment as a risk factor for opioid dependence: Comparison of family characteristics and type and severity of child maltreatment with a matched control group. Child Abuse and Neglect, 33(6), 343-352.
  3. Maloney, E., Degenhardt, L., Darke, S., and Nelson, E., (2009). Are non-fatal opioid overdoses misclassified suicide attempts? Comparing the associated correlates. Addictive Behaviors, 34(9), 723-729.  
  4. Maloney, E., Degenhardt, L., Darke, S., and Nelson, E., (2009). Impulsivity and borderline personality as risk factors for suicide attempts among opioid-dependent individuals.  Psychiatry Research, 169, 15-21.
  5. Shand, F., Degenhardt, L., Slade, T., & Nelson, E. (2009). The structure of polysubstance dependence and its correlates in a heroin dependent sample (abstract). Drug and Alcohol Review, 28, A58-A58.
  6. Shand, F. Slade, T., Degenhardt, L., & Nelson, E.C. (2009). The severity of heroin dependence: does it exist and is it clinically relevant? Drug and Alcohol Review, 28, A58-A58.
  7. Shand, F., Degenhardt, L., Nelson, E. & Mattick, R.P., (2010). Predictors of social anxiety in an opioid dependent sample and a matched control group. Journal of Anxiety Disorders, 24, 49-54.
  8. Maloney, E., Degenhardt, L., Darke, S., & Nelson, E. (2010). Investigating the co-occurrence of self-mutilation and suicide attempts among opioid dependent individuals and matched controls. Suicide and Life Threatening Behavior, 40(1), 50-62.
  9. Shand F, Degenhardt L, Slade T, Mattick RP, Nelson EC. (2010). Comorbidity and severity of heroin dependence: untangling the impact of each on overdose, suicidality, treatment history and criminality. Drug And Alcohol Review, 29, 68-68.
  10. Shand, F., Degenhardt, L., Slade, T., & Nelson, E.N. (2011). Sex differences amongst dependent heroin users: Histories, clinical characteristics and predictors of other substance dependence. Addictive Behaviors, 36(1-2), 27-36.
  11. Shand, F., Slade, T., Degenhardt, L., Baillie, A., & Nelson, E.N. (2011). Opioid dependence latent structure: two classes with differing severity? Addiction, 106(3), 590-598.
  12. Agrawal, A., Nelson, E.C., Littlefield, A., Bucholz, K., Degenhardt, L., Henders, A., Madden, P., Martin, N., Montgomery, G., Pergadia, M., Sher, K., Heath, A., & Lynskey, M. (2012). Cannabinoid receptor genotype moderation of the effects of childhood physical abuse on anhedonia and depression. Archives of General Psychiatry, 69(7), 732-740. doi:10.1001/archgenpsychiatry.2011.2273
  13. Panagopoulos, V., Trull, T., Glowinski, A., Lynskey, M., Heath A., Agrawal, A., Henders, A., Wallace, L., Todorov, A., Madden, P., Moore, E., Degenhardt, L., Martin, N., Montgomery, G., & Nelson, E. (2013). Examining the Association of NRXN3 SNPs with borderline personality disorder phenotypes in heroin dependent cases and socioeconomically disadvantaged controls. Drug and Alcohol Dependence, 128, 187-193.
  14. Nelson, E., Lynskey, M., Heath, A., Wray, N., Agrawal, A., Shand, F., Henders, A., Wallace, L., Todorov, A., Schrage, A., Saccone, N., Madden, P., Degenhardt, L., Martin, N., Montgomery, G. (2013). ANKK1, TTC12, and NCAM1 Polymorphisms and heroin dependence: Importance of considering drug exposure. JAMA Psychiatry, 70(3), 325-33.
  15. Nelson, E., Lynskey, M., Heath, A., Wray, N., Agrawal, A., Shand, F., Henders, A., Wallace, L., Todorov, A., Schrage, A., Madden, P., Degenhardt, L., Martin, N., Montgomery, G., (2014). Association of OPRD1 Polymorphisms with Heroin Dependence in a Large Case-control Series. Addiction Biology, 19(1) 111-121.
  16. Nelson, E.C., Heath, A., Lynskey, M., Agrawal, A., Henders, A., Todorov, A., Madden, P., Moore, E., Degenhardt, L., Martin, N.G. & Montgomery, G., (2014). PTSD risk associated with a functional DRD2 polymorphism in heroin dependent cases and controls is limited to amphetamine dependent individuals. Addiction Biology, 19(4), 700-707.
  17. Shand, F.L., Christensen, H., Moore, E., Ridani, R., Degenhardt, L., & Nelson, E.C. (in press accepted June 24th 2013). The link between childhood exposure to violence and suicidality. Journal of Affective Disorders.
  18. Shand, F., Rawlinson, W., Degenhardt, L., Day, C., Martin, N., & Nelson, E.N. (2014). Hepatitis C testing and status among opioid substitution treatment clients in New South Wales. Australian and New Zealand Journal of Public Health, 38(2), 160-164.
  19. Hancock, D., Levy, J., Gaddis, N., Glasheen, C., Saccone, N., Page, G., Hulse, G., Wildenauer, D., Kelty, E., Schwab, S., Degenhardt, L., Martin, N., Montgomery, G., Attia, J., Holliday, E., McEvoy, M., Scott, R., Bierut, L., Nelson, E., Kral, A., & Johnson, E., (2015). Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1. Biological Psychiatry, 78, 474–484.
  20. Carey, C., Agrawal, A., Zhang, B., Conley, E., Degenhardt, L., Heath, A., Li, D., Lynskey, M., Martin, N., Montgomery, G., Wang, T., Bierut, L., Hariri, A., Nelson, E., & Bogdan, R. (2015). Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis. Journal of Abnormal Psychology, 124, 860-877.
  21. Werner, K., McCutcheon, V., Challa, M., Agrawal, A., Lynskey, M., Conroy, E., Statham, D., Madden, P., Henders, A., Todorov, A., Heath, A., Degenhardt, L., Martin, N., Bucholz, K., & Nelson, E. (2015). The association between childhood maltreatment, psychopathology, and adult sexual victimization in men and women: results from three independent samples. Psychological Medicine, 46(3), 563-573.
  22. Kristjansson, S., McCutcheon, V., Agrawal, A., Lynskey, M., Conroy, E., Statham, D., Madden, P., Henders, A., Todorov, A., Bucholz, K., Degenhardt, L., Martin, N., Heath, A. & Nelson, E., (2016). The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders. Brain and Behavior, 6(2), 1-11.
  23. Lintzeris, N., Moodley, R., Campbell, G., Bruno, R., Larance, B., Nielsen, S., & Degenhardt, L. (2016). Sleep quality among people living with chronic non-cancer pain: Findings from the Pain and Opioids IN Treatment (POINT) cohort. Clinical Journal of Pain 32(5), 80-87.
  24. Nelson, E., Agrawal, A., Heath, A., Bogdan, R., Sherva, R., Zhang, B., Al-Hasani, R., Bruchas, M., Chou, Y.-L., Demers, C., Carey, C., Conley, E., Fakira, A., Farrer, L., Goate, A., Gordon, S., Henders, A., Hesselbrock, V., Kapoor, M., Lynskey, M., Madden, P., Moron, J., Rice, J., Saccone, N., Schwab, S., Shand, F., Todorov, A., Wallace, L., Wang, T., Wray, N., Zhou, X., Degenhardt, L., Martin, N., Hariri, A., Kranzler, H., Gelernter, J., Bierut, L., Clark, D., & Montgomery, G. (2016). Evidence of CNIH3 involvement in opioid dependence. Molecular Psychiatry, 21(5), 608-614.
  25. Schwantes-An T., Zhang J., Chen L., Hartz S.M., Culverhouse R.C., Chen X., Coon H., Frank J., Kamens H.M., Konte B., Kovanen L., Latvala A., Legrand L.N., Maher B.S., Melroy W.E., Nelson E.C., Reid M.W., Robinson J.D., Shen P., Yang B., Andrews J.A., Aveyard P., Beltcheva O., Brown S.A., Cannon D.S., Cichon S., Corley R.P., Dahmen N., Degenhardt, L. et al. (2016). Association of the OPRM1 variant rs1799971 (A118G) with non-specific liability to substance dependence in a collaborative de novo meta-analysis of European-ancestry cohorts. Behavior Genetics, 46(2), 151-169.
  26. Larney, S., Cama, E., Nelson, E. Larance, B., & Degenhardt, L. (2016). A cross-sectional study of correlates of imprisonment in opioid dependent men and women in New South Wales, Australia. Drug and Alcohol Review, 35(6), 686-692.
  27. Agrawal, A., Chou, Y-L., Carey, C., Baranger, D., Zhang, B., Sherva, R., Wetherill M., Kapoor, M., Wang, J., Bertelsen, S., Anokhin, A., Hesselbrock, V., Kramer, J., Lynskey, M., Meyers, J., Nurnberger, J., Rice, J., Tischfield, J., Bierut, L., Degenhardt, L., Farrer, L., Gelernter, J., Hariri, A., Heath, A., Kranzler, H., Madden, P., Martin, N,. Montgomery, G., Porjesz, B., Wang, T., Whitfield, J., Edenberg, H., Foroud, T., Goate, A., Bogdan, R., & Nelson, E. (2018). Genomewide association study identifies novel locus for cannabis dependence. Molecular Psychiatry, 23(5), 1293-1302.
  28. Crist, R., Doyle, G., Nelson, E., Degenhardt, L., Martin, N., Montgomery, G., Saxon, A., Ling, W., & Berrettini, W. (2018). A polymorphism in the OPRM1 3’ untranslated region is associated with methadone efficacy in treating opioid dependence. Pharmacogenomics Journal, 18(1), 173-179.
  29. Pikovsky, M., Peacock, A., Larance, B., Larney, S., Conroy, E., Nelson, E., & Degenhardt, L. (2018). Alcohol use disorder and associated physical health complications and treatment amongst individuals with and without opioid dependence: A case-control study. Drug and Alcohol Dependence, 188, 304-310.
  30. Larance, B., Gisev, N., Larney, S., Cama, E., Darke, S., Nelson, E., & Degenhardt, L. (2018). Predictors of transitions across stages of heroin use, dependence and treatment seeking among an opioid-dependent sample. Drug and Alcohol Dependence, 191, 145-151.
  31. Agrawal, A., Chou, Y.-L., Carey, C. E., Baranger, D. A. A., Zhang, B., Sherva, R., Wetherill, L., Kapoor, M., Wang, J.-C., Bertelsen, S., Anokhin, A. P., Hesselbrock, V., Kramer, J., Lynskey, M. T., Meyers, J. L., Nurnberger, J. I., Rice, J. P., Tischfield, J., Bierut, L. J., … Nelson, E. C. (2018). Genome-wide association study identifies a novel locus for cannabis dependence. Molecular Psychiatry, 23(5), 1293–1302. https://doi.org/10.1038/mp.2017.200. 
  32. Karagiannis, T. T., Cleary, J. P., Gok, B., Henderson, A. J., Martin, N. G., Yajima, M., Nelson, E. C., & Cheng, C. S. (2020). Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program. Nature Communications, 11(1), 1–10. 
  33. Polimanti, R., Walters, R. K., Johnson, E. C., Mcclintick, J. N., Adkins, A. E., Adkins, D. E., Bacanu, S.-A., Bierut, L. J., Bigdeli, T. B., Brown, S., Bucholz, K. K., Copeland, W. E., Costello, E. J., Degenhardt, L., Farrer, L. A., Foroud, T. M., Fox, L., Goate, A. M., Grucza, R., … Gelernter, J. (2020). Leveraging genome-wide data to investigate differences between opioid use vs. Opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. Molecular Psychiatry, 25(8), 1673–1687. https://doi.org/10.1038/s41380-020-0677-9.
  34.  Johnson, E. C., Demontis, D., Thorgeirsson, T. E., Walters, R. K., Polimanti, R., Hatoum, A. S., Sanchez-Roige, S., Paul, S. E., Wendt, F. R., Clarke, T.-K., Lai, D., Reginsson, G. W., Zhou, H., He, J., Baranger, D. A. A., Gudbjartsson, D. F., Wedow, R., Adkins, D. E., Adkins, A. E., … Agrawal, A. (2020). A large-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet Psychiatry, 7(12), 1032–1045. https://doi.org/10.1016/S2215-0366(20)30339-4.
  35.  Sherva, R., Zhu, C., Wetherill, L., Edenberg, H. J., Johnson, E., Degenhardt, L., Agrawal, A., Martin, N. G., Nelson, E., Kranzler, H. R., Gelernter, J., & Farrer, L. A. (2021). Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes. Exploration of Medicine. https://doi.org/10.37349/emed.2021.00032. 
  36. Santo Jr, T., Gisev, N., Campbell, G., Nelson, E., & Degenhardt, L. (Under Review). The effects of childhood trauma and mental disorders on treatment engagement, contact with the criminal justice system, and mortality among people with opioid dependence. Drug and Alcohol Dependence.


Santo Jr, Thomas, Natasa Gisev, Gabrielle Campbell, & Louisa Degenhardt The effects of childhood trauma and mental disorders on treatment engagement, contact with the criminal justice system, and mortality among people with opioid dependence. Lisbon Addictions European Conference on Addictive Behaviours and Dependence. 23-25 November 2022. (Accepted) Lisbon, Portugal. 


The CATS study seeks to provide a better understanding of the genetics of opioid dependence. The data linkage component of the study will examine underlying and contributing causes of death among this cohort of opioid dependent people, in addition to factors (i.e. demographics, childhood and adult victimisation, and psychiatric disorders) that predict mortality and engagement in OST. The analysis of data from opioid dependent cases and non-opioid dependent controls will provide unique insight into the role of opioid dependence and opioid substitution therapy in mortality risk.

Project Research Area: 
Drug Type: 
Project Status: