Comorbidity and Trauma Study (CATS)
NDARC Staff
Richard Mattick, Louisa Degenhardt, Fiona Shand, Elizabeth Conroy, Elizabeth Maloney, Michelle Torok, Caitlin McCue, Cherie Kam, Gregory French
Other Investigators
Elliot Nelson, Michael Lynskey and Andrew Heath (Washington University), Nick Martin (Queensland Institute of Medical Research), William Rawlinson (Department of Microbiology, Prince of Wales Hospital)
Rationale
Opiate dependence is a major societal problem worldwide that is often associated with increased criminal activity, overdose, and physical and mental health problems.
Opiate dependence risk has a strong genetic component. However, no reports thus far have definitively demonstrated an association of the presence of one or more specific genes with opiate dependence risk. Further, opiate dependent persons report extremely high rates of childhood trauma. Genetically-informative designs have suggested that childhood trauma is often followed by the development of substance dependence. Animal investigations have also confirmed that early trauma may be associated with greater levels of use of opiates (when these substances are available). These investigations suggest that this relationship may be biologically mediated with the hypothalamic-pituitary axis particularly implicated.
Aims
The study aimed to:
- Identify polymorphisms and/or mutations in candidate genes to be typed in cases and controls
- Assess retrospectively childhood trauma to enable its inclusion as a risk modifying variable
- Analyse genotype and interview data to test for candidate gene effects on opioid dependence, and the moderation by history of childhood trauma
- Identify patterns of comorbidity amongst cases and controls
Design and Method
This was a case-control genetic association study of opioid dependence with the inclusion of childhood trauma history as a potential confounding variable. Researchers interviewed and collected blood samples from 1500 opioid dependent cases and 500 non-dependent controls, matched by age, sex and employment status. Childhood trauma and psychiatric comorbidities were measured by a computerised, structured interview which will enable DSM-III and DSM-IV-R diagnoses to be made. Participants were recruited over 3.5 years, with interviews being conducted at NDARC, methadone clinics, and community centres in the greater Sydney area.
The study was conducted in collaboration with Washington University, St Louis; the Queensland Institute of Medical Research, Brisbane; and the Prince of Wales Hospital, Randwick. NDARC was responsible for the collection of blood samples and interview data from participants, and the genetic analysis occurred at QIMR and Washington University.
Benefits
The design of the study will allow for the identification of genes associated specifically with opioid dependence. The interaction between genes and environmental risk factors will also be tested. In addition, the extensive interview data collected will enable a thorough examination of the characteristics of the population, as well as relationships between mental health, childhood trauma, polydrug dependence, and suicidality. Finally, the prevalence and risk factors for the Hepatitis C virus will be assessed, and the genetic data will be part of a larger international study examining the genes associated with clearance versus chronicity of HCV.
Output
Elizabeth Maloney has completed a thesis examining suicidality. Elizabeth Conroy has completed a thesis examining the associations between childhood maltreatment and mental health in this population. A third thesis by Fiona Shand examining the relationship between polysubstance dependence and mental health is underway. Several peer-reviewed manuscripts have been published, accepted or submitted. The genetic analysis is currently underway.
Funding
National Institute of Drug Abuse (National Institutes of Health), USA