Exploring the relative contribution of alcohol/drug dependence and depression on the immune system: The DARCY Study Priscilla Martinez, Mphil 1,2 ; Anne Landheim, PhD 3 ; Jørgen Bramness, MD, PhD 1, Lars Lien, MD, PhD 2,4 1 Senter for rus- og avhengighetsforsking, SERAF, UiO, 2 Avdeling for rusrelatert psykiatri og avhengighet, Sykehuset Innlandet 3 Kompetansesenter rus region øst, 4 Institutt for klinisk medisin, UiO 1 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no Immunendring kan gi depresjon 30-04-2010 Depresjon og psykose kan være forårsaket av immunendringer som skjer ved blant annet infeksjoner, allergier, revmatiske lidelser, hjerte-karsykdom eller metabolsk syndrom. Lisbeth Nilsen 2 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 1
Background Depression the result of changes in cytokine profiles, and the cytokine profile of depressed persons is different than nondepressed. cytokine profile Depression Immune system Alcohol and drug dependence compromise the immune system, mediated through changes in cytokine profiles. Alcohol dependence cytokine profile Immune system 3 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no Background Substance dependence and depression are often co-morbid. Alcohol Dep. Depression The impact of each disorder on the immune system in the context of the other needs more investigation.?????? Alcohol Dep. Depression?????? Immune system 4 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 2
Objectives To observe differences in serum cytokine levels between alcohol and drug dependent persons with and without depression. To observe differences in serum levels of cytokines between pure alcoholics with and without depression. To observe differences in levels of cytokines between serum polysubstance abusers with and without depression. To observe differences in levels of cytokines between pure alcoholics and poly-substance abusers stratified by depression status. 5 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no Methods Study sites and participants Patients admitted to Utredningsenhenten (D2) at Sanderud (Sykehuset Innlandet), Behandlingsenter at Sørlihaugen (Sykehuset Innlandet), Blå Kors behandlingsenter at Eina Avdeling for depressive lidelser og komplisert sorg at Modum Bad Riisby behandlingsenter Participants are treatment seeking non-psychotic alcohol/substance abusers OR depressed persons.. 6 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 3
Methods Study procedures Employees at recruitment site approach patients about the study and obtain informed consent. Blood and urine samples collected. Self-administered structured questionnaire given to participant to complete during stay. Measures include SCL-90-R, AUDIT, DUDIT, Alcohol Time Line Follow Back, BenDep, questions on health, disease and smoking status. Demographics and CIDI diagnoses obtained through a medical chart review OR an face-to-face interview. Serum samples tested for the cytokines interleukin (IL)-1, IL-6, TNFa, and IL-10. 7 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no So far Recruitment ongoing at Utredningsenheten, Sanderud. Planned recruitment for Riisby and Modum Bad this Autumn. 82 patients enrolled 70:30 male:female Average age 32 years 68% from Hedmark/Oppland 8 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 4
pro-inflammatory cytokine level (U/L) serum cytokine level 25.10.2010 Hypotheses We hypothesize cytokine levels will be highest among dependent persons with depression and lowest among healthy controls without depression. We also hypothesize cytokine levels will be higher among persons with depression than healthy dependents without depression. 9 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no Other potential results 10 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 5
Alternative associations Co-morbid depression may alone account for the immune changes observed in substance dependent persons. Depression may contribute its own effect on immune changes distinct from the effect from substance dependence. The substance dependence may fully account for immune changes, that is, depression may play a minor role, where depression may be a substance dependence related affective disorder distinct from classic major depression. 11 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no Implications What would these results mean for our theoretical understanding of the relationship between the brain and the immune system? What would they mean clinically? 12 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 6
Theoretical Lend further support to the interconnectivity between the immune and nervous systems. Contribute to the early evidence of immune changes attributable to depression in the context of substance abuse in particular. Add evidence to which cytokines may or may not be involved in mediating the communication between the immune system and the brain. 13 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no Clinical Certain cytokines may serve diagnostic purposes for presence and severity of depression, where the level for clinical significance may vary between the general population and substance dependent persons. Cytokines measurements may not be clinically relevant among a substance dependent population. Treating substance users for depression may have positive immunological consequences. Pharmacological interventions may use cytokine production and receptors as targets. 14 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 7
Other considerations Lifestyle factors play a large role in immune function. There is little clinical research on immune changes in persons with depression and co-morbid substance dependence. There is more research conducted as preclinical studies, such as animal models and ex vivo laboratory studies. 15 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no In summary The DARCY study aims to better understand the contribution of depression and substance dependence on changes in the immune system. The results of this study can further the theoretical underpinnings of how the immune and nervous systems interact. This is one step among many towards identifying potential diagnostic and curative applications exploiting the relationship between immune changes and depression in the context of substance dependence. 16 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 8
Thank you 17 SERAF - Senter for rus- og avhengighetsforskning www.seraf.uio.no 9