Chemical Exposures That May Cause Depression

Agricultural Workers & Pesticides

At 55 years old, Matt Peters, an Iowa farmer, took his own life.[1] While there are known to be higher rates of depression amongst agricultural workers, his wife Ginny noticed that every year his mood shifted towards depression in the spring at the time when he sewed his field with pesticide-treated seeds and believes pesticide exposure may have caused this annual change in demeanor.[2] While this story, by itself, is anecdotal and does not prove correlation, in the past 30 years, a growing body of research has emerged exploring the relationship between chemical exposure and depression.

The etiology of depression is believed to be determined by a variety of influences including environmental, social, and genetic.[3] In 2012 and 2015, compared to the general occupational rate of 17.3 per 100,000, the highest suicide rates of 44.9 and 32.2 per 100,000 were found in those that worked in the agricultural, fishing, and forestry sectors.[4] The notion that there may be a relationship between depression in farmers and pesticides use emerged 30 years ago when Beseler et al., (2008) conducted a study from 1993 to 1997, and found farmers with cumulative high-intensity pesticide exposure were associated with higher rates of depression compared to controls.[5]

Pesticides are designed to be toxic by targeting systems of rodents, weeds, fungi, or insects - and these impacts can potentially be damaging to human systems, as well.[6] In 2013, Freire & Koifman conducted a systematic review of epidemiological evidence and found five studies that showed a statistically significant increased risk of psychiatric disorders associated with previous pesticide poisonings.[7] The same review found four studies demonstrating that in areas with intensive pesticide use there was an increased risk of suicide, though the authors recommend future prospective studies be conducted to explore these relationships.[8] These findings were similar to other reports including a 2008 study conducted by Browning et al. which found that White male farmers residing in North Carolina, South Carolina, and Kentucky had higher rates of suicide than the general White male population residing in the same states.[9] The epidemiological team led by Beard et al. (2014) found that out of 19,506 agricultural workers studied, depression was linked to those who used seven individual pesticides which fell into two specific classes: organochlorine insecticides and fumigants.[10] Diagnosis of depression was 90% more likely amongst farmers who used organochlorine insecticides and it was up 80% for those who used fumigants.[11] Similarly, Reed et al. (2020) conducted a systematic search of literature published from June 2019 to January 2020 and found thirteen studies on the relationship between exposure to pesticides/chemicals and the risk of depression/suicide.[12]

Based on their research, Reed et al., note that the awareness of depression in agricultural workers may prove especially challenging to address in rural areas where access to mental health may already be limited.[13] Additionally, despite a growing body of research exploring this correlation, conclusive results require further research. Previously published studies often use self-report methods which can make clear thresholds difficult to determine.[14] While most researchers conclude further scientific studies are needed on this topic, they simultaneously encourage occupational health providers to be aware of farm exposures that may influence symptoms of depression.[15]

Pregnancy & Early Childhood Development

Jacobsen et al., (2022) note that research indicates that women in both pregnancy and postpartum periods experience an increased susceptibility to environmental chemicals exposures.[16] Bisphenol A (BPA) and phthalates are sometimes referred to as “everywhere chemicals” because of their presence in ordinary products manufactured from polycarbonate plastics.[17] BPA is an endocrine-disrupting chemical that is often found in drink containers, sales receipts, and medical devices.[18] Even at low doses, it is known to interfere with hormone balances (via multiple steroid hormone receptors that mediate a myriad of cellular effects).[19]

Any chemicals that are endocrine disruptors can affect endogenous hormone levels, which may be more substantial during the dramatic psychological and hormonal changes that take place during pregnancy, delivery and childbirth.[20] In looking at the impacts of persistent organic pollutants, Jacobsen et al. (2022) found that studies analyzing the results of exposure to polybrominated diphenyl ethers (a class of chemicals used to increase fire resistance in household products)[21] during pregnancy consistently showed an increase in symptoms of perinatal depression.[22] It is recommended that further study in this area, including biospecimen collection and biomarkers, are needed to further understand this relationship.[23]

There are also indications that maternal chemical exposures during pregnancy and early childhood exposure may have ongoing impacts on mental health in later life. In children, there is evidence indicating that postnatal BPA exposure may be linked to other neurobehavioral impairments such as attention-deficit hyperactivity disorder (ADHD).[24] Perera et al. (2016) conducted an analysis of BPA in a group of mothers in Northern Manhattan from pregnancy through the first 10-12 years of the child’s age, monitoring levels of BPA in urine during the third trimester of pregnancy with follow up analysis of the children’s urine at ages 3 and 5.[25] The research showed significant positive association between higher levels of prenatal BPA and higher levels of anxiety and depression in boys 10-12 years of age with no corresponding relationship in girls.[26]

Lead exposure is another chemical exposure believed to impact mental health and may come through contaminated water, paint, mining, pottery, smoking, and industrial processes.[27] Children tend to absorb a higher amount of ingested lead than adults, and since lead accumulates in the body throughout life and is released slowly, exposure in early childhood and adolescence can have impacts later in life.[28] Research conducted by Bouchard et al. (2009) found young adults with blood-lead levels in the highest quintile were found to have 2.3 times the odds of being diagnosed with major depressive disorder.[29] A study conducted in Jintan, China involving 1,341 children showed that increased lead levels were associated with emotional problems, developmental problems, and anxiety.[30] Similar research from New Zealand indicates that early-life exposure during the era of leaded gasoline may have contributed to subtle changes in emotion and behavior.[31] The study followed 579 people for more than 30 years found a relationship between lead exposure and the development of depression, mania, phobia, and schizophrenia.[32] Lead in gasoline has since been banned in most countries, and while earlier exposure cannot be reversed, this information can be used to screen individuals with earlier lead exposure for symptoms of depression and provide treatment options that can improve their quality of life.[33]

While examining any chemical impacts on mental health, it is important to note that research is still emerging, and findings are sometimes mixed. A systematic review conducted by Cybulska et al. (2021) on the relationship between cadmium and lead levels in blood with symptoms of depression found that while nine out of thirteen studies did show an association between lead levels and depression there are many factors that can influence both the blood levels and the psychological diagnosis indicating the need for further research.[34]

Industrial Occupational Exposure

Occupational and environmental exposures to polychlorinated biphenyls (PCBs) have been shown to be related to symptoms of depression.[35] In the US, production of PCBs was banned by the Toxic Substances Control Act (TSCA) in 1979.[36] In international production, this group of chemicals (which was commonly used in manufacturing during the 20th century) was banned worldwide in 1995 by the United Nations Environmental Programme, but due to their high persistence, they can still be detected in the environment and exposure can occur in occupations that work with older electronic devices.[37] EPA regulations within the US also allow for the inadvertent generation of some PCBs under specified concentrations and conditions with required reporting to the EPA.[38]

The dangers of PCB exposure have been known for some time with the World Health Organization (WHO) stating in 1985 that exposure to organic solvents were known to be associated with memory complaints, sleep disturbance, depression, irritability, attention deficits, and fatigue.[39] Studies in both humans and animals show evidence that PCBs can influence the dopamine system leading to depressive symptoms.[40] A German study conducted by Gaum et al. (2017), collected data from 178 participants examining occupational exposure to high levels of PCB over a one-year period and found a positive correlation of PCB exposure with severity of depressive symptoms mediated by lower concentrations of homovanillic acid found in blood plasma as a surrogate biomarker for dopamine.[41] This analysis provides the foundation for a potential causal pathway between PCB exposure and increases in depression.[42] Products produced before 1979 that may contain PCBs include plastics, cable insulation, oil-based paints, transformers, electrical equipment, adhesives, floor finish and carbonless copy paper.[43]

PCBs are only one type of persistent organic pollutants (POPs) which are known to cause depression and anxiety after chronic exposure.[44] In comparison, both acute and chronic exposure to nonpersistent organic chemicals (including organometals, organophosphates, and solvents) are believed to be linked to more severe psychiatric symptoms which not only include depression and anxiety, but can also include psychosis, mania and aggression.[45] Research conducted by Saraei et al. (2022) studied 396 industrial workers to determine whether there was a relationship between solvent exposure (in the form of benzene, xylenes, ethyl benzene, and toluene) and depression.[46] This analysis showed that workers with a significant association of solvent exposure showed a high frequency of depressive symptoms.[47] It is recommended that individuals and clinicians be aware of potential psychiatric impacts following chemical exposures due to chemical accidents, solvent inhalation, or community exposure.[48]

Air Pollution & Global Mental Health

In addition to direct chemical exposure, there is growing research indicating that higher rates of specific types of air pollution may be associated with increases in depression both in the general population and specified age groups through either a direct or indirect causal pathway. An analysis conducted by Qiu et al. (2023) of those who lived in specified US zip codes found that prolonged exposure to high levels of air pollutants was linked to an increased risk of new diagnoses for depression in adults age 64 and older.[49] The cohort study analyzed data collected from 8,907,422 Medicare participants from 2005-2016 and found that for every increase in five units of long-term mean exposure to the air pollutants ozone (O3), nitrogen dioxide (NO2), and small particulate matter measuring ≤2.5 μm (PM2.5) was associated with a statistically significant increase in depression.[50] One potential pathway for this relationship is that the pollution exposure causes increased levels of oxidative stress in the brain, which then activates the hypothalamic-pituitary-adrenal axis, which can trigger the release of stress hormones and lead to depression.[51] These findings can potentially have implications on a global level since most of the world’s population are believed to reside in areas where particulate matter exceeds recommendations of the World Health Organization (WHO).[52]

A similar study conducted by Petkus et al. (2020) on three-year exposure to PM2.5 in 2,202 women aged 67-83 found a significant correlation between PM2.5 exposure and accelerated declines in free-recall memory and verbal learning, but no significant association with depressive symptoms.[53] However, there were associations found between reductions in episodic memory and increased symptoms of depression indicating that PM2.5 exposure may indirectly increase symptoms of depression.[54]

The American Psychological Association warns that exposure over time to the air pollutant ozone may be linked to increased depressive symptoms in adolescents.[55] The study conducted by Manszak et al. (2022) tracked whether neighborhood ozone levels over a four-year period affected depressive symptoms in 213 adolescents aged 9-13 at the beginning of the study.[56] Results indicated adolescents who lived in neighborhoods with higher levels of ozone showed increases in symptoms of depression even when ozone fell within acceptable levels of exposure by both state and national air quality standards.[57]

Additional research suggests exposure to air pollutants may be associated with higher rates of depression in the general population. A meta-analysis conducted by Borroni et al. (2022) looked at 39 studies and found an increased risk of depression associated with long term exposure to PM2.5 and nitrogen dioxide NO2.[58] Depressive symptoms were also found to be associated with short-term exposure to other air pollutants including sulfur dioxide (SO2), ozone (O3), carbon monoxide (CO) and particulate matter measuring ≤10 μm (PM10).[59] These findings correlate with research conducted by Szyszkowicz et al. (2009) in Canada showing an increase in emergency room visits for depression on days with higher levels of the ambient pollutants carbon monoxide, nitrogen dioxide, and sulfur dioxide.[60]

Practical Steps

Psychiatric disorders, including depression, are believed to have increased over 18% between 2005 and 2015, affecting 300 million people worldwide.[61] Research is still being conducted to evaluate whether further environmental factors influence depression, including noise pollution, urbanization, electromagnetic fields and pollen.[62] In contrast, there are also some indications that exposure to natural environments may have a calming effect that can potentially reduce the risk of depression.[63] Since it is generally considered healthy to be outdoors, being aware of what pollutants may be in the area (e.g., using weather alerts to monitor outdoor air quality) may allow individuals to still receive the mental health benefits of spending time outdoors while reducing exposure to potential pollutants.

While it may not be possible for an individual to isolate themselves from all potential chemical exposures, some precautions can be taken to avoid unnecessary risk. Individuals working with hazardous chemicals should read warning labels and adhere to safety guidelines utilizing personal protective equipment when recommended.

Regardless of known chemical exposure, if a person experiences symptoms of depression such as feeling sad, hopeless, anxious, or worthless it is advisable to speak with a licensed medical professional to determine if psychotherapy or medication may be beneficial.[64]

Contributed by: Theresa Nair

Editor: Jennifer (Ghahari) Smith, Ph.D.

REFERENCES

1 Bienkowski B. High rates of suicide, depression linked to farmers' use of pesticides. Scientific American Web site. https://www.scientificamerican.com/article/high-rates-of-suicide-depression-linked-to-farmers-use-of-pesticides/. Updated 2014. Accessed March 15, 2023.

2 Ibid.

3 van den Bosch M, Meyer-Lindenberg A. Environmental exposures and depression: Biological mechanisms and epidemiological evidence. Annual Review of Public Health. 2019;40(1):239-259. https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-040218-044106. doi: https://doi.org/10.1146/annurev-publhealth-040218-044106.

4 Reed DB, Claunch DT. Risk for depressive symptoms and suicide among U.S. primary farmers and family members: A systematic literature review. Workplace Health & Safety; Workplace Health Saf. 2020;68(5):236-248. doi: 10.1177/2165079919888940.

5 Beseler CL, Stallones L, Hoppin JA, et al. Depression and pesticide exposures among private pesticide applicators enrolled in the agricultural health study. ENVIRON HEALTH PERSP. 2008;116(12):1713-1719. doi: 10.1289/ehp.11091.

6 van den Bosch & Meyer-Lindenberg (2019)

7 Freire C, Koifman S. Pesticides, depression and suicide: A systematic review of the epidemiological evidence. Int J Hyg Environ Health. 2013;216(4):445-460. https://www.sciencedirect.com/science/article/pii/S1438463912001393. doi: 10.1016/j.ijheh.2012.12.003.

8 Ibid.

9 Reed & Claunch (2020)

10 Beard JD, Umbach DM, Hoppin JA, et al. Pesticide exposure and depression among male private pesticide applicators in the agricultural health study. Environ Health Perspect. 2014;122(9):984-991. doi: 10.1289/ehp.1307450.

11 Bienkowski (2014)

12 Reed & Claunch (2020)

13 Ibid.

14 van den Bosch & Meyer-Lindenberg (2019)

15 Reed & Claunch (2020)

16 Jacobson MH, Ghassabian A, Gore AC, Trasande L. Exposure to environmental chemicals and perinatal psychopathology. Biochem Pharmacol. 2022;195:114835. https://www.sciencedirect.com/science/article/pii/S0006295221004512. doi: 10.1016/j.bcp.2021.114835.

17 van den Bosch & Meyer-Lindenberg (2019)

18 Perera F, Nolte ELR, Wang Y, et al. Bisphenol A exposure and symptoms of anxiety and depression among inner city children at 10-12 years of age. Environ Res. 2016;151:195-202. doi:10.1016/j.envres.2016.07.028

19 Mustieles V, Messerlian C, Reina I, Rodríguez-Carrillo A, Olea N, Fernández aMF. Is bisphenol A (BPA) a threat to children's behavior? Journal of Mental Health & Clinical Psychology. 2018;2(1). https://www.mentalhealthjournal.org/articles/is-bisphenol-a-bpa-a-threat-to-childrens-behavior.html. Accessed Mar 28, 2023.

20 Jacobsen et al. (2022)

21 Center for Disease Control (CDC). Polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls (PBBs) factsheet | national biomonitoring program | CDC. https://www.cdc.gov/biomonitoring/PBDEs_FactSheet.html. Updated 2021. Accessed Mar 28, 2023.

22 Jacobsen et al. (2022)

23 Ibid.

24 Mustieles et al. (2018)

25 Perera et al. (2016)

26 Ibid.

27 Bouchard MF, Bellinger DC, Weuve J, et al. Blood lead levels and major depressive disorder, panic disorder, and generalized anxiety disorder in US young adults. Arch Gen Psychiatry. 2009;66(12):1313-1319. doi:10.1001/archgenpsychiatry.2009.164

28 CDC (2021)

29 Bouchard et al. (2009)

30 Shute N. Lead exposure may cause depression and anxiety in children. National Public Radio (NPR) Web site. https://www.npr.org/sections/health-shots/2014/06/30/326940022/lead-exposure-causes-anxiety-and-depression-in-chinese-children. Updated 2014. Accessed March 15, 2023.

31 Mozes A. Https://Www.webmd.com/mental-health/news/20190123/childhood-lead-exposure-raies-mental-rises-later. Web MD Web site. https://www.webmd.com/mental-health/news/20190123/childhood-lead-exposure-raies-mental-rises-later. Updated 2019. Accessed March 15, 2023.

32 Harvard. Study finds link between childhood lead exposure and mental illness. News Web site. https://www.hsph.harvard.edu/news/hsph-in-the-news/childhood-lead-exposure-mental-illness/. Updated 2019. Accessed Mar 28, 2023.

33 Mozes (2019)

34 Cybulska AM, Grochans S, Kamińska MS, Bosiacki M, Skonieczna-Żydecka K, Grochans E. Are cadmium and lead levels linked to the development of anxiety and depression? - A systematic review of observational studies. Ecotoxicol Environ Saf. 2021;216:112211. https://www.sciencedirect.com/science/article/pii/S0147651321003225. doi: 10.1016/j.ecoenv.2021.112211.

35 Gaum PM, Gube M, Esser A, Schettgen T, Quinete N, Bertram J, Putschögl FM, Kraus T, Lang J. Depressive Symptoms After PCB Exposure: Hypotheses for Underlying Pathomechanisms via the Thyroid and Dopamine System. International Journal of Environmental Research and Public Health. 2019; 16(6):950. https://doi.org/10.3390/ijerph16060950

36 United States Environmental Protection Agency (EPA). Learn about polychlorinated biphenyls (PCBs). https://www.epa.gov/pcbs/learn-about-polychlorinated-biphenyls-pcbs. Updated 2022. Accessed Mar 28, 2023.

37 Gaum et al. (2019)

38 EPA (2022)

39 Saraei M, Golshan M, Aminian O. Association between solvent exposure and depression among industrial workers | SpringerLink. Journal of Public Health. 2022;30:953-958. https://link.springer.com/article/10.1007/s10389-020-01376-y#citeas. Accessed Mar 17, 2023. doi: https://doi.org/10.1007/s10389-020-01376-y.

40 Gaum et al. (2019)

41 Ibid.

42 Ibid.

43 EPA (2022)

44  Brown Jr. JS. Psychiatric effects of organic chemical exposure. In: Effects of persistent and bioactive organic pollutants on human health. ; 2013:514-531. https://doi.org/10.1002/9781118679654.ch19. 10.1002/9781118679654.ch19.

45 Brown (2013)

46 Saraei et al. (2022)

47 Ibid.

48 Brown (2013)

49 O’Mary L. Air pollution linked to depression in older adults: Study. WebMD Web site. https://www.webmd.com/depression/news/20230213/air-pollution-linked-depression-older-adults-study. Accessed Mar 28, 2023.

50 Qiu X, Shi L, Kubzansky LD, et al. Association of Long-term Exposure to Air Pollution With Late-Life Depression in Older Adults in the US. JAMA Netw Open. 2023;6(2):e2253668. doi:10.1001/jamanetworkopen.2022.53668

51 Ibid.

52 Ali NA, Khoja A. Growing Evidence for the Impact of Air Pollution on Depression. Ochsner J. 2019;19(1):4. doi:10.31486/toj.19.0011

53 Petkus AJ, Younan D, Widaman K, et al. Exposure to fine particulate matter and temporal dynamics of episodic memory and depressive symptoms in older women. Environ Int. 2020;135:105196. https://www.sciencedirect.com/science/article/pii/S0160412019313613. doi: 10.1016/j.envint.2019.105196.

54 Ibid.

55 American Psychological Association (APA). Air pollution linked to depressive symptoms in adolescents. American Psychological Association (APA) Web site. https://www.apa.org/news/press/releases/2022/03/air-pollution-adolescents. Updated 2022. Accessed Mar 28, 2023.

56 Manczak E, Miller J, Gotlib IH. Census tract ambient ozone predicts trajectories of depressive symptoms in adolescents. American Psychological Association. 2022. https://www.apa.org/pubs/journals/releases/dev-dev0001310.pdf. Accessed Mar 28, 2023.

57 APA (2022)

58 Borroni E, Pesatori AC, Bollati V, Buoli M, Carugno M. Air pollution exposure and depression: A comprehensive updated systematic review and meta-analysis. Environmental Pollution. 2022;292:118245. https://www.sciencedirect.com/science/article/pii/S0269749121018273. doi: 10.1016/j.envpol.2021.118245.

59 Ibid.

60 Szyszkowicz, M., Rowe, B. H., & Colman, I. (2009). Air pollution and daily emergency department visits for depression. International journal of occupational medicine and environmental health, 22(4), 355–362. https://doi.org/10.2478/v10001-009-0031-6

61 Ali & Khoja (2019)

62 van den Bosch & Meyer-Lindenberg (2019)

63 Ibid.

64  National Institute of Mental Health (NIMH). Depression. National Institute of Mental Health (NIMH) Web site. https://www.nimh.nih.gov/health/topics/depression. Updated 2022. Accessed Mar 28, 2023.