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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
J Occup Environ Med. Author manuscript; available in PMC Oct 1, 2007.
Published in final edited form as:
PMCID: PMC1626656




This nested case control study evaluated the association between depression and pesticide exposure among women.


The study population included 29,074 female spouses of private pesticide applicators enrolled in the Agricultural Health Study between 1993–1997. Cases were women who had physician diagnosed depression requiring medication. Lifetime pesticide use was categorized as never mixed/applied pesticides, as low exposure (up to 225 days), high exposure (>225 days) and a history of diagnosed pesticide poisoning.


After adjustment for state, age, race, off-farm work, alcohol, cigarette smoking, physician visits and solvent exposure, depression was significantly associated with a history of pesticide poisoning (OR 3.26; 95% CI 1.72, 6.19) but not low (OR 1.09; CI 0.91, 1.31) or high (OR 1.09; 95% CI 0.91, 1.31) cumulative pesticide exposure.


Pesticide poisoning may contribute to risk of depression.

Keywords: pesticides, depression, Agricultural Health Study, female farm residents

Studies over the past forty years show an association between neurological effects and exposure to organophosphate (OP) insecticides 13. In the past decade, several studies have suggested a possible association between pesticide exposure and depressive symptoms, particularly among cases of acute poisoning 47. Depression associated with a pesticide poisoning may persist for years after the poisoning 4,8. Some studies have shown long-term effects on mood in the absence of an acute pesticide poisoning 6,911, but others have not 1214. Thus reported effects of pesticide exposure on depression are inconsistent, and information on effects from low-dose, long-term exposure is especially meager.

The association of depression with pesticide exposure has been demonstrated primarily in studies of men, and the few studies of women have suffered from limited power 4,5,11. The epidemiology of depression in women is different than in men 15. Women have a lifetime prevalence rate of depression of 20% compared to 10% in men 16, and depression in women occurs at younger ages, lasts longer, and is more frequently associated with stressful life events than depression in men 1518. Risk factors for depression in women include a family or personal past history of mood disorders, loss of a parent before age 10, a childhood history of physical or sexual abuse, persistent psychosocial stresses and the loss of social support 15,16. Female farm spouses have additional burdens associated with financial hardship, heavy seasonal workloads, working off as well as on the farm, and exposures to chemicals that may be associated with depression 19,20.

A few studies have characterized the chemical and environmental exposures of farm spouses. In a cross-sectional survey conducted in Colorado between 1993 and 1997, 37% of female spouses of principal farm operators reported working in crop production 21. A cross-sectional survey of 657 farm women in southeast Louisiana reported that 88.9% were involved in the management and oversight of the farm operation, 60.3% cared for farm animals, 70.8% cared for and used farm equipment and 42.5% were involved in crop management 19. Previously published data from the Agricultural Health Study (AHS), a longitudinal study of commercial pesticide applicators and farm residents, showed that 68% of Iowa spouses and 54% of North Carolina spouses mixed or applied pesticides with a median cumulative exposure of 50 lifetime days 22.

The AHS provided the opportunity to study pesticide exposures occurring in the course of farm work undertaken by women and to evaluate whether cumulative pesticide exposure, or a history of acute pesticide poisoning, was associated with physician diagnosed depression.


Data for this study come from spouses of private pesticide applicators, mainly farmers, enrolled in the AHS, a cohort study of 89,658 participants designed to study effects of agricultural exposures on health outcomes 23. A total of 32,347 spouses of private farmer applicators enrolled in the study between 1993 and 1997 in Iowa and North Carolina 23. They completed detailed questionnaires and returned them by mail (81%) or responded by phone (19%) 22. Details of the questionnaire can be obtained at the AHS website (www.aghealth.org).

Because the epidemiologic characteristics of depression differ in women and men, and because few spouses were men, male spouses were excluded from the analyses. Spouses who were missing responses to the diagnosed depression question, who reported a previous lead or solvent poisoning 24 or head injury 25, or who were under 18 years of age were also excluded. A total of 29,074 women were available for analysis after these exclusions.

Cases were defined as female spouses of private applicators who responded “yes” to the question “Has a DOCTOR ever told you that you had been diagnosed with depression requiring medication”. Controls were female spouses who responded “no”. For those responding “yes”, age of diagnosis was obtained in 20-year categories.

Based on associations reported in the literature on depression, and to control for potential confounding, factors chosen for inclusion in the analyses were age at enrollment, state of residence, education, race, Hispanic ethnicity, cigarette smoking and alcohol use. Visits to a physician during the past 12 months was also considered because frequent visits to a physician may increase the probability of being diagnosed with depression (26). Race was dichotomized into white and non-white with whites being the reference group. Education was categorized as whether or not the respondent finished high school, age into four groups (less than 40 years, 40 to 49 years, 50 to 59 years and greater than 59 years, with those under 40 as the reference group), current alcohol use into never/rarely, monthly, weekly or daily, and cigarette smoking status as never, past, or current.

Farm and work history information included the number of years a person lived or worked on a farm, whether the respondent lived on a farm 10 years prior to enrollment, whether the respondent ever held a job off the farm, the amount of time spent at the job held the longest, potential exposures to pesticides, and exposure to solvents from the non-farm job held the longest. Individuals who worked with pesticides were asked whether they personally mixed or applied pesticides less than 50% or 50% or more of the time, number of years and days per year of mixing or applying pesticides, and the specific chemicals used. Information on history of pesticide poisoning was obtained by asking, “Has a DOCTOR ever told you that you had been diagnosed with pesticide poisoning?”

Lifetime use of any pesticide was calculated by multiplying number of years of use by the number of days per year of use. Individuals below the 90th percentile of lifetime use (225 days) were classified as experiencing low-level exposure, while those above the 90th percentile were assigned high-level exposure. Those with a history of pesticide poisoning were considered as a separate category, regardless of the number of lifetime days of use. Thus there were four pesticide exposure categories: never mixed or applied pesticides (referent group); low-level cumulative exposure; high-level cumulative exposure; and a history of pesticide poisoning.

Demographic, behavioral and exposure characteristics for cases and controls were evaluated by univariate analyses using logistic regression. Age, cigarette smoking, current alcohol use and visits to a doctor were coded as indicator variables (0 if no visits, 1 if one visit and 2 if more than one visit) to obtain odds ratios (OR) and 95% confidence intervals (CIs) for effects over categories. Multivariable logistic regression analysis was used to determine whether a pesticide exposure category was associated with diagnosed depression, controlling for the demographic and behavioral factors and solvents and other exposures that were significantly associated with depression in the univariate analyses. ORs with 95% CIs are reported from the univariate and multivariate analyses.

Individual pesticides were initially examined in four broad categories: as ever use of insecticides, herbicides, fumigants and fungicides. Insecticide products included permethrin, terbufos, fonofos, trichlorfon, lindane, carbofuran, chlorpyrifos, malathion, parathion, carbaryl, diazinon, aldicarb, phorate, aldrin, chlordane, dieldrin, DDT, heptachlor, toxaphene, coumaphos, and dichlorvos. Herbicide products included atrazine, dicamba, cyanazine, chlorimuron ethyl, metolachlor, EPTC, alachlor, metribuzin, paraquat, petroleum oil, pendimethalin, imazethapyr, glyphosate, 2,4,5 T P, butylate, trifluralin, 2,4-D, and 2,4,5 T. Fungicide products included benomyl, chlorothalonil, captan, maneb, metalaxyl, and ziram. Fumigant products included methyl bromide, aluminum phosphide, carbon tetrachloride/carbon disulfide and ethylene dibromide. Secondly, a principal component analysis (PCA) was used to create groupings of related-use pesticides. Specific chemicals were considered correlated with each factor if they had a factor loading of 40 or greater, which represents approximately a 15% overlap of the variance in pesticide use with the factor. Factors were considered significant if they had eigenvalues greater than one. The factors were used in unadjusted and adjusted logistic regression models to determine whether they were associated with diagnosed depression.

All analyses were conducted using SAS, version 8.2, SAS Institute, Cary, North Carolina. The August 2, 2002, release of the AHS phase I dataset was used in these analyses. This work was conducted with approval from the Institutional Review Board of Colorado State University.


There were 2,051 (7.1% of the population) self-reported cases of diagnosed depression requiring medication. The prevalence of diagnosed depression was significantly higher in North Carolina (8.1%) than in Iowa (6.6 %) with an unadjusted OR of 1.25 (CI 1.14, 1.37) (Table 1). This difference was largely eliminated after adjusting for smoking, alcohol use, and number of visits to a doctor (OR 1.04; CI 0.94, 1.16).

Table 1
Associations of depression with demographic, behavioral, and pesticide exposure characteristics in 29,074 Iowa and North Carolina female spouses of farmer pesticide applicators, AHS, 1993–1997; unadjusted odds ratios (ORs) with 95% confidence ...

Depression was more common among whites and older women and among those without a high school education, using alcohol or tobacco, having more doctor visits, and having worked off the farm (Table 1). The number of years lived on farms did not differ between cases and controls (mean 31.9 years with a standard deviation of 18 years). Cases were more likely to have personally mixed or applied pesticides than controls, but unadjusted ORs among those who mixed or applied pesticides more than 50% of the time were not greater than among those who mixed or applied less frequently (Table 1). Cases were more likely to have been exposed to solvents or to have personally applied pesticides to their home or lawn (Table 1).

Unadjusted ORs for depression were 1.11 (CI 1.01, 1.22) among those mixing or applying for up to 225 days, 1.22 (CI 1.02, 1.45) for greater than 225 days and 3.97 (CI 2.18, 7.21) among those reporting a history of pesticide poisoning. Depression was significantly associated with the use of insecticides, fumigants, and fungicides, and nearly significant for herbicides (Table 1).

In multivariable models, items significantly associated with the risk of depression included race, age, alcohol use, cigarette smoking, number of doctor visits in the past year, solvent exposure and history of pesticide poisoning (Table 2). Adjusting percent of time personally mixing or applying pesticides by the same covariates used in Table 2 in separate analyses, showed a reduction in the size and precision of the association of (applying < 50%: OR 1.06 CI 0.94–1.20 applying ≥ 50%: OR 1.08 CI 0.95–1.23; mixing < 50%: OR 1.13 CI 1.00–1.28 mixing > 50%: OR 1.06 CI 0.91–1.24). In adjusted models, ORs (95% CIs) were elevated but statistically insignificant for insecticides (1.09, 0.99–1.20), herbicides (1.07, 0.97–1.18), fumigants (1.25, 0.91–1.72) and fungicides (1.12, 0.91–1.38). The risk of depression from pesticide poisoning was relatively unaffected by adjusting for different covariates or stratifying by state (Table 3).

Table 2
Association of diagnosed depression with pesticide exposure in female spouses of private pesticide applicators, controlling for demographic and behavioral characteristics shown to be significant in the univariate analysis AHS, 1993–1997 (n=1966 ...
Table 3
Association of diagnosed depression with pesticide exposure by state of residence, female spouses of private applicators, AHS, 1993–1997.

A separate analysis was conducted excluding the 27 women who reported a history of pesticide poisoning but responded negatively to the question about personal use of pesticides, although ten of these women reported that they personally treated their homes or lawns for pests in another section of the questionnaire. ORs for history of pesticide poisoning and diagnosed depression remained elevated after excluding the 27 women, but both effect size and precision were reduced in univariate models (OR 1.74, CI 0.61, 4.92) and after adjusting for state of residence, race, age, ever worked a job off the farm, doctor visits, cigarette smoking, current alcohol use and solvent exposure (OR 1.56, CI 0.54, 4.56).

The PCA identified four significant factors (Table 4). Factor 1, which explained most of the variance of pesticide use with an eigenvalue of 14.9, was composed of thirteen herbicides, three OP insecticides and one carbamate. This factor was not associated with diagnosed depression in a univariate logistic regression model, or after adjustment for state of residence, race, age, ever worked a job off the farm, doctor visits, cigarette smoking, current alcohol use and solvent exposure (Table 5). Factor 2 was correlated with four organochlorine insecticides, Factor 3 with two OP insecticides, one carbamate insecticide and two herbicides and Factor 4 with one fumigant and three fungicides (Table 5). In unadjusted analyses, Factors 3 and 4 showed weak, but statistically significant, associations with depression (Table 5). After adjustment for the above covariates, none of the factors were associated with depression (Table 5).

Table 4
Factor loadings from principal components analysis of individual pesticides in female spouses of private pesticide applicators, AHS, 1993–1997.
Table 5
Association of diagnosed depression with individual factors derived from PCA of pesticides used by female spouses of private applicators, AHS, 1993–1997. *


In this study, a history of pesticide poisoning was significantly associated with self-reported physician diagnosed depression among female spouses of private pesticide applicators, after controlling for other risk factors. The association was observed in both Iowa and North Carolina. The association with depression was considerably stronger among individuals with past pesticide poisoning episodes than among individuals with no such reported episodes. This finding is similar to the reports on neuropsychological outcomes that addressed mood disorders 13,14,2628 where individuals with pesticide exposure, but no history of poisoning, showed few mood disorders, but mood disorders have been observed in those with a history of a high level of exposure or a history of poisoning 46,29.

At the low and high cumulative exposure levels observed in this study, no association was observed with depression in adjusted models. Potential misclassification of exposure is always a concern and it is impossible to know whether a history of depression would create a differential bias, which could either inflate or reduce the OR in the two-level exposure variable.

The prevalence of self-reported physician diagnosed depression in this study (7.1%) was similar to the prevalence of 6% to 8% of diagnosed depression found in studies of primary care medical practices. Using diagnosed depression as the outcome may select for those with major depression, rather than dysthymic disorder or intermittent, milder episodes of depression 18,30. Previous work has shown that major depression is the type most frequently diagnosed by a physician 31. Physicians tend to under-recognize depression in their patients, and only one-third to two-thirds of depressed individuals are diagnosed with depression by a primary care physician 3234. Because symptoms may be transitory, previous cross-sectional studies using standardized scales may have identified a broader range of depression types. Agricultural workers may underutilize mental health resources due to the complexities of farm life, further contributing to failure to detect mild depression 35. Under diagnosis of depression in this farming population would result in the misclassification of cases of depression as non-cases and attenuate the OR observed in this study.

Non-pesticide risk factors for depression in this population were similar to those in previous studies of farm residents. Age, health status, current smoking, binge drinking, involvement with farm work, and working a job off the farm have been associated with depressive symptoms in several farming communities 19,3638.

Although the frequency and duration of pesticide exposure among female spouses in the AHS was generally lower than among the licensed applicators, the cohort includes a subset of spouses who may have pesticide exposures quite similar to those of their applicator husbands 22. Women who reported at least one lifetime application day, and those with no history of pesticide poisoning had a median number of lifetime-exposure days of 50.8 while those who reported a pesticide poisoning had a median number lifetime-exposure days of 8.8. The low median number of days in the poisoned groups makes it unlikely that low-dose, long-term exposure is acting as a confounder of pesticide poisoning 14, particularly since 27 of the 63 women with poisonings reported no use of pesticides and another 25 had < 225 days of use.

Twenty-seven women, who reported a history of poisoning, reported never having personally mixed or applied pesticides. However, in a separate section of the questionnaire, eight of these women reported personally treating their homes and two reported personally treating their lawns for pests. Treating one’s home for pests was associated with diagnosed depression in this study. The fact that 18.8% of the women who responded that they used pesticides in the home or on pets did not report personally mixing or applying pesticides suggests that some pesticide exposures may be missed when questions are asked in the context of agricultural use. Domestic use of pesticides may be an important source of pesticide poisoning. Excluding the 27 women who reported poisoning, but no farm-related use from the analysis reduced the association of pesticide use with depression. This suggests that domestic poisonings have important health consequences. Alternatively, it is possible that a woman with a pesticide poisoning but no pesticide use might have used pesticides in a suicide attempt.

This study suggests that the association of pesticides with depression was more likely to be related to insecticides, fungicides, or fumigants and less likely associated with herbicides or organochlorine insecticides. Thirteen herbicides loaded onto Factor 1, but three OPs and one carbamate did so also. The organochlorine insecticides loaded separately on Factor 2 with an OR of one and were least likely to be associated with depression. This supports the finding of Savage et al., 1988, where no association of neurological effects with measured organochlorine pesticide residues was observed in a group of pesticide-poisoned applicators 4. Factors 3 and 4 showed a very weak association to depression. Perhaps this is not surprising since the factors are based on use patterns of pesticides and not on possible risk for depression. Additionally, chemical mixtures and solvents added to the pesticide may play a role in contributing to the associations observed in this study. The PCA analysis herein excluded male spouses and demographic variables, making the results of the PCA in this study different from the factor analysis of the AHS cohort published by Samanic et al., 2005 39.

The literature implicates OPs as one candidate for depressive effects 1,4,9,40, but few studies have reported on other classes of pesticides and depression. The effects of OPs on acetylcholinesterases are well known, but animal studies also indicate that other carboxylesterases exist in the central nervous system that are more sensitive to OPs than acetylcholinesterases 41,42. There is also evidence that certain OPs may target neuropeptide metabolism in the central nervous system 43,44. Recently OP compounds were shown to inhibit lysophospholipases, such as neuropathic target esterase (NTE), which is the putative target of OP-induced delayed neuropathy 4547. This inhibition increases the levels of lysolecithin in the cell, resulting in demyelination of axons and alterations in signaling from the cell membrane 45,48.

The strengths of this study include the large number of cases of diagnosed depression and the detailed questionnaire containing information on pesticide use history and other risk factors for depression. Limitations include the cross-sectional study design and the use of self-reported information for both physician-diagnosed depression and diagnosed pesticide poisoning. Information on the date of diagnosis of depression and on the date of pesticide poisoning was available only in 20-year age categories restricting our ability to make inferences about temporality.

Despite these limitations, this study suggests that farm women, who are not themselves licensed applicators, and who generally spend less time mixing and applying pesticides than farmer applicators, have an increased odds of having a physician diagnosed depression in the presence of a history of pesticide poisoning. This study highlights the importance of preventing pesticide poisoning since the chronic effects of those poisonings may contribute to high rates of depression.


This research was supported (in part) by the Intramural Research Program of the NIH (National Cancer Institute and National Institute of Environmental Health Sciences.


Cheryl L. Beseler, PhD, Mailman School of Public Health, Biostatistics Department, Division of Statistical Genetics, 722 West 168th Street, 6th Fl., New York, NY 10032

Contributor Information

Cheryl Beseler, Colorado Injury Control Research Center, Department of Psychology, Colorado State University, Fort Collins, Colorado; Mailman School of Public Health, Biostatistics Department, Columbia University, New York, New York phone: 212-342-2884 e-mail ude.aibmuloc@9112blc; cbeseler@lamar,colostate.edu.

Lorann Stallones, Colorado Injury Control Research Center, Department of Psychology, Colorado State University, Fort Collins, Colorado.

Jane A. Hoppin, Epidemiology Branch, National Institutes of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina.

Michael C.R. Alavanja, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland.

Aaron Blair, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland.

Thomas Keefe, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado.

Freya Kamel, Epidemiology Branch, National Institutes of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina.


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