1. Organophosphate exposure as a risk factor for suicide attempts Leslie London 1, Zelda Holtman 1, John Joska 2, Laila Asmal 3, Bonga Chiliza 3, Peter Smith 4, Raj Ramesar 5, Lorann Stallones 6 1 Centre for Environmental and Occupational Health Research, School of Public Health and Family Medicine, University of Cape Town 2 Department of Psychiatry and Mental Health, University of Cape Town 3 Department of Psychiatry, University of Stellenbosch 4 Division of Pharmacology, Department of Medicine, University of Cape Town 5 Division of Human Genetics, University of Cape Town 6 Department of Psychology, Colorado State University

2. Colliding problems Pesticide poisoning + suicide WHO: 1 million unintentional and 2 million intentional annual pesticide poisonings; 220 000 deaths. Majority: –Occupational exposures –Intentional exposure (suicide and para- suicide) –Non-occupational accidental exposures WHO: 800 000 suicide deaths annually; Affects millions 2 nd leading cause of death for 15-29 years In SA > 5000 death p/a

3. Suicide using pesticides Accounts for about 33% of suicides globally

5. Pesticides and Suicide: Unresolved Questions 1.Pesticides are readily accessible 2.We know that pesticides are potent and toxic agents used FOR suicide 3.But could pesticides be causual or contributory to Suicide Risk? 4.The relationship between suicide and exposure to pesticides

6. A possible causal link between OP exposure and depression? 1.Clinical case series provide support. 2.OP´s = known CNS neurotoxins, acute and chronic 3.Animal data show a link OP exposure and serotonin. Serotonin disturbance associated with depression. 4.Acute OP poisoning  can result in neuropsychiatric effects compatible with affective disorders 5.Long-term low dose exposure may effect psychiatric state and affect. 6.NB effects most sensitive for symptom outcomes, closely linked to affective disorders. 7.Literature: Three ecological studies; 2 C-C studies; 1 SMR study.

7. Suicide Depression OP Exposure Model 1:

8. Suicide Impulsivity OP Exposure Model 2:

9. Suicide Model 3: Impulsivity OP Exposure Depression

10. Suicide OP Exposure Impulsivity Model 4: Depression Ready Availability in Farming Areas

11. OP´s and Suicide - Mortuary Study Unpublished, Motlagomang, 2007 7427 unnatural deaths 1995-99; missing data for 36% Death rates per 100 000 from suicide: –Amonst farm workers: 68.9 –Amongst general SA population: 3.4 - 39.9 –Relative Risk farm workers 3.8  1.7 (min) to 5.3 (max)  i.e. Farm workers 5 times more likely to use pesticides for suicide

12. Case control study - OP exposure and Suicide attempts 1.Aim: To investigate whether exposure to organophosphate pesticides plays a role in the causation of attempted suicide –Primary hypothesis - long-term exposure to Organophosphate (OP) Insecticides is associated with an increased risk of attempting suicide, irrespective of the means of suicide; –A dose response exists in exposure – effect relationship 2.Design: Hospital-based case-control study, using two teaching hospitals in Cape Town 3.Sample Size 200 cases and 200 controls 4.Cases: Adults only, with diagnosis meeting ICD Codes, E950 to E959, admitted Controls: Matched gender, age and admission date for condition other than suicide

13. Exposure measures: Detailed history of occupational and non-occupational exposure to OP pesticides Hair samples for DAP and DMP metabo lites Confounders measured: Age, education, income Religious affiliation and SES Smoking, alcohol consumption (AUDIT) Medical history HIV status and sexual orientation Psychiatric scales: Impulsivity (Barrat), Depression (CES-D), Aggression (Buss-Perry), Suicidal Ideation (SSI) in controls only.

14. Preliminary findings 135 participants thus far –66% female –Median age 30; median schooling 11 years –71 cases, 64 controls –14% risky drinking on AUDIT –25% HIV+

15. Cases (n=71)Controls (n=64) Females62%66%NS Age in years31.4 (10.3)31.4 (9.8)NS Schooling in years10.4 (2.1)10.4 (2.5)NS Xhosa speaking42%39%NS Afrikaans speaking35%42%NS English speaking21%16%NS AUDIT ≥1614% NS Current Smoker52%34%P=0.04 Employed75%63%NS Domestic pesticide use85%88%NS Garden pesticide use13%16%NS HIV +ve (n=107)24%27%NS

16. Psychiatric scales Cases (n=71)Controls (n=64) Aggression score: Buss-Perry (Mean; SD) 37 (9.4)37 (11.1)NS Impulsivity elevated score 54%36%p = 0.03 Depression score: CES-D 33.8 (11.6)25.9 (10.5)p<0.01

17. Exposure assessment: hair as marker of long-term exposure 28 samples:21% 22 analysable17% 7 outliers NOT SO SIMPLE!!

18. DMP and DAP metabolites Cases (n=11)Controls (n=11) Median (range) log transformed DMP 0.22 (0.15-0.58) 0.70 (0.41-0.95) P=0.02 Median (range) log transformed DAP 0.46 (0.42-0.76) 0.75 (0.22-1.29) NS Inverse association with DMP metabolites!!

19. Discussion and Conclusion Suicide attempt associated with increased impulsivity and depression No association aggression or  AUDIT No association with history of pesticide exposure HIV prevalence 24% to 27% Hair metabolites yielding inverse relationship Early days yet (recruitment at 33%)

20. Acknowlegements: Funders: American Foundation for Suicide Prevention National Research Foundation Staff at collaborating hospitals Patients willing to be interviewed