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Pesticides and Mental Health
Bibliography
Amr, M.M, Halim, Z.S. & Moussa, S.S. (1997). Psychiatric
disorders among Eqyption pesticide applicators and formulators. Environmental
Research. 73, 193-199.
Two hundred eight pesticide formulators, 172 pesticide applicators,
and 223 control subjects (72 from an urban region matching the
pesticide formulators and 151 from a rural area matching the
pesticide applicators) underwent psychiatric assessment. The study
aimed to screen for psychiatric morbidity using a standardized
screening tool, the General Health Questionnaire, and a widely
recognized system of diagnosis and classification, the revised third
edition of the Diagnostic and Statistical Manual of Psychiatric
Disorders (DSM-III-R). Significantly higher frequencies of
psychiatric disorders were found in the exposed groups. The
predominant diagnosis was depressive neurosis; the most frequent
symptoms were irritability and erectile dysfunction. Theoretical and
practical implications of these findings are discussed.
Link: http://www.unc.edu/~eckerman/Amr.pdf
Beseler, C.L. & Stallones, L. (2008). A Cohort Study of Pesticide
Poisoning and Depression in Colorado Farm Residents. Ann Epidemiol.
2008 Aug 8. [Epub ahead of print]
PURPOSE: Depressive symptoms have been associated with pesticide
poisoning among farmers in cross-sectional studies, but no
longitudinal studies have assessed the long-term influence of
poisoning on depressive symptoms. The purpose of this study was to
describe the associations between pesticide poisoning and depressive
symptoms in a cohort of farm residents. METHODS: Farm operators and
their spouses were recruited in 1993 from farm truck registrations
using stratified probability sampling. The Center for Epidemiologic
Studies-Depression scale was used to evaluate depression in
participants using generalized estimating equations. Baseline
self-reported pesticide poisoning was the exposure of interest in
longitudinal analyses. RESULTS: Pesticide poisoning was significantly
associated with depression in three years of follow-up after
adjusting for age, gender, and marital status (odds ratio [OR] 2.59;
95% confidence interval [CI] 1.20-5.58). Depression remained elevated
after adjusting for health, decreased income, and increased debt (OR
2.00; CI 0.91-4.39) and was primarily due to significant associations
with the symptoms being bothered by things (OR 3.29; CI 1.95-5.55)
and feeling everything was an effort (OR 1.93; CI 1.14-3.27).
CONCLUSIONS: Feeling bothered and that everything was an effort were
persistently associated with a history of pesticide poisoning,
supportive of the hypothesis that prolonged irritability may result
from pesticide poisoning.
Beseler, C., Stallones, L., Hoppin, J.A., Alavanja, M.C.R., Blair,
A., Keefe, T., & Kamel, F. (2008). Depression and pesticide
exposures among privatel pesticide applicators enrolled in the
Agricultural Health Study. Environmental Health
Perspectives. 116(12), 1713-1719.
Background: We evaluated the relationship between diagnosed
depression and pesticide exposure using information from private
pesticide applicators enrolled in the Agricultural Health Study
between 1993 and 1997 in Iowa and North Carolina.
Methods: There were 534 cases who self-reported a physician-diagnosed
depression and 17,051 controls who reported never having been
diagnosed with depression and did not feel depressed more than once a
week in the past year. Lifetime pesticide exposure was categorized in
three mutually exclusive groups: low (< 226 days, the reference
group), intermediate (226-752 days), and high (> 752 days). Two
additional measures represented acute high-intensity pesticide
exposures: an unusually high pesticide exposure event (HPEE) and
physician-diagnosed pesticide poisoning. Logistic regression analyses
were performed relating pesticide exposure to depression.
Results: After adjusting for state, age, education, marital status,
doctor visits, alcohol use, smoking, solvent exposure, not currently
having crops or animals, and ever working a job off the farm,
pesticide poisoning was more strongly associated with depression
[odds ratio (OR) = 2.57 ; 95% confidence interval (CI), 1.74-3.79]
than intermediate (OR = 1.07 ; 95% CI, 0.87-1.31) or high (OR = 1.11
; 95% CI, 0.87-1.42) cumulative exposure or an HPEE (OR = 1.65 ; 95%
CI, 1.33-2.05). In analysis of a subgroup without a history of acute
poisoning, high cumulative exposure was significantly associated with
depression (OR = 1.54 ; 95% CI, 1.16-2.04).
Conclusion: These findings suggest that both acute high-intensity and
cumulative pesticide exposure may contribute to depression in
pesticide applicators. Our study is unique in reporting that
depression is also associated with chronic pesticide exposure in the
absence of a physician-diagnosed poisoning.
Link: http://www.medscape.com/viewarticle/586331
or http://www.medscape.com/viewarticle/586331_print
Beseler, C., Stallones, L., Hoppin, J.A., Alavanja, M.C.R., Blair,
A., Keefe, T., & Kamel, F. (2006). Depression and pesticide
exposures in female spouses of licensed pesticide applicators in the
Agricultural Health Study cohort. J. Occup. Environ Med, 48(10),
1005-1013..
Objective
This nested case control study evaluated the association between
depression and pesticide exposure among women.
Methods
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.
Results
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.
Conclusion
Pesticide poisoning may contribute to risk of depression.
Link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1626656
or http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1626656&blobtype=pdf
Biskind, M. & Bieber, I. (1949). DDT poisoning: A new syndrome
with neuropsychiatric manifestations. American Journal of Psychotherapy,
, 261- .
Link: http://www.whale.to/a/biskind11.html
Colosio, C., Tiramani, M., & Maroni, M. (2003).
Neurobehavioral effects of pesticides: State of the art. NeuroToxicology
24, 577-591.
The authors have reviewed the literature on neurobehavioral toxicity
of pesticides to assess the status of knowledge on this matter. Some
data suggest that exposure to DDT and fumigants may be associated
with permanent decline in neurobehavioral functioning and increase in
psychiatric symptoms, but, due to the limited number of studies
available and the scarce knowledge on exposure levels, no firm
conclusion can be drawn. Data on subjects acutely poisoned with
organophosphorous compounds suggest that an impairment in
neurobehavioral performance and, in some cases, emotional status may
be observed as a long-term sequela, but the possibility still remains
that these effects were only an aspecific expression of damage and
not of direct neurotoxicity. Studies carried out on subjects
chronically exposed to organophosphates, but never acutely poisoned,
do not provide univocal results but the slight changes consistently
observed in sheep dippers suggest the need of focusing on activities
characterized by relatively higher exposure levels. In general, the
main limits of existing knowledge are the variability of the testing
methods used, which makes it difficult to compare the results of
single studies, and the scarce knowledge on exposure levels. A
promising approach may be the conduction of prospective longitudinal
or cohort studies, where exposure and dose assessment can be more
easily controlled, or the evaluation of cohorts of workers a priori
selected for the availability of environmental and biological
monitoring data. The follow up of the populations under study may
give an answer at the problem of the prognostic significance of the
observed changes. Also the protocols used to assess neurobehavioral
functioning need to be standardized.
Conyers, R.A. & Goldsmith, L.E. (1971). A case of
organophosphorus-induced psychosis. Med J Aust. 1(1), 27-9.
Davies, R., Ahmed, G., & Freer, T. (2000). Chronic exposure to
organophosphates: background and clinical picture. Advances
in Psychiatric Treatment. 6, 187-192.
[Does not have an Abstract. Starts with a section called Case Study.]
A male farmer in his forties from the Irish Republic was referred for
an opinion on his mood swings and their possible relationship with
organophosphate exposure. He had been regularly exposed to
organophosphorus sheep dips for around 15 years prior to the assessment.
His personal history until he became ill, four years prior to
assessment, was unremarkable. There was no previous psychiatric
history or any of substance misuse. He was happily married and,
although not well-off, had no financial difficulties. There was no
family psychiatric history.
Approxiamtely 10 years prior to assessment, he began to develop
flu-like symptoms following each dipping lasting 2–3 days but
these were not in any sense incapacitating. Four years prior to
interview he developed a particularly severe bout of this lasting
4–5 days, characterised by disorientation, sweating, excessive
salivation and diarrhoea and followed by a two-week period of apathy,
depression, muscular aches and pains and fasciculation. Subsequently,
there were two further such episodes and during this time the
following symptom pattern developed.
His mood became markedly unstable with brief swings into both tearful
depression and extreme irritability. These periods generally lasted
for hours only, although against a background from time to time of
more protracted periods of low-grade depression of mood. He also
experienced several episodes of impulsive suicidal thinking and on
one occasion ‘came to’ in his yard holding a loaded shotgun
to his mouth. A variety of antidepressants were tried, but with no,
or only transient benefit. Adverse effects were prominent at
relatively low dose.
His short-term memory and attention became impaired, with him
frequently getting lost and forgetting what he intended to do. He
stopped reading completely, a pastime which he previously enjoyed,
because of his inability to concentrate and retain the plot. His wife
was obliged to take on most of the farm paperwork.
He became profoundly sensitive to the presence of perfumes and
similar substances and also very sensitive to the effects of alcohol.
Prior to becoming ill, he was a social drinker only, but subsequently
small quantities of alcohol had such a great effect on him that his
frequent state of inebriation led to his admission for
detoxification. It was a very brief stay indeed since it became
rapidly clear to the treating psychiatrist that there was no alcohol
dependence problem. Subsequent to his discharge, he stopped drinking
alcohol. He also became highly sensitive to the presence of low
concentrations of organophosphates to the point that he was unable to
go to sheep sales. He described one episode of muscular twitching,
excessive salivation, headache and abdominal cramps when in the
vicinity of a passing flock of newly-dipped sheep.
His handwriting deteriorated markedly in legibility, with numerous
spelling mistakes that previously he would not have made. He
subsequently developed a significant word-finding disorder. His
ability to sustain muscular activity became seriously impaired, to
the point that he was barely able to carry out the most basic chores
on the farm.
On this basis, he was diagnosed as suffering from the
neuropsychiatric effects of organophosphate exposure (Ahmed &
Davies, 1997).
Approximately six months after assessment he shot himself.
At post-mortem, evidence of extensive peripheral neuropathy
compatible with an organophosphate aetiology but unlike the picture
of alcoholic polyneuropathy was found.
Link: http://apt.rcpsych.org/cgi/reprint/6/3/187.pdf
Eskenazi, B., Rosas, L.G., Marks, A.R., Bradman, A., Harley, K.,
Holland, N., et al. (2008). Pesticide toxicity and the developing
brain. Basic and Clinical Pharmacology and Toxicology, 102, 228-236.
Abstract:
Organochlorine pesticides are used in some countries for malaria
control and organophosphate pesticides are widely used in agriculture
and in homes. Previous literature documents children’s exposure
to these chemicals both in utero and during development. Animal
studies suggest that many of these chemicals are neurodevelopmental
toxicants even in moderate doses, but there are few studies in human
beings. Associations of children’s pesticide exposure with
neurodevelopment from studies being conducted worldwide are
summarized. In addition, we present the work of the CHAMACOS study, a
longitudinal birth cohort study of Mexican-American children living
in the Salinas Valley of California. In this study, we investigated
the relationship of children’s neurodevelopment with maternal
dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene
serum levels, as well as prenatal and child organophosphate urinary
metabolite levels. We have examined the association with
children’s performance on the Brazelton Neonatal Assessment
Scales and at 6, 12 and 24 months on the Bayley Scales of Infant
Development (mental development and psychomotor development) and
mothers report on the Child Behaviour Checklist. We observed a
negative association of prenatal dichlorodiphenyltrichloroethane
exposure and child mental development. We also observed adverse
associations of prenatal but not postnatal organophosphate pesticide
exposure with mental development and pervasive developmental disorder
at 24 months.
Grigoryan, H., Schopfer, L.M., Thompson, C.M., Terry, A.V., Masson,
P. & Lockridge, O. (2008). Mass spectrometry identifies
covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl
fluorophosphate, and FP-biotin to tyrosines on tubulin: A potential
mechanism of long term toxicity by organophosphorus agents. Chemico-Biological
Interactions, 175, 180-186
Chronic low dose exposure to organophosphorus poisons (OP) results in
cognitive impairment. Studies in rats have shown that OP interfere
with microtubule polymerization. Since microtubules are required for
transport of nutrients from the nerve cell body to the nerve synapse,
it has been suggested that disruption of microtubule function could
explain the learning and memory deficits associated with OP exposure.
Tubulin is a major constituent of microtubules. We tested the
hypothesis that OP bind to tubulin by treating purified bovine
tubulin with sarin, soman, chlorpyrifos oxon,
diisopropylfluorophosphate, and 10-fluoroethoxyphosphinyl-N-biotinamidopentyldecanamide
(FP-biotin). Tryptic peptides were isolated and analyzed by mass
spectrometry. It was found that OP bound to tyrosine 83 of alpha
tubulin in peptide TGTYR, tyrosine 59 in beta tubulin peptide YVPR,
tyrosine 281 in beta tubulin peptide GSQQYR, and tyrosine 159 in beta
tubulin peptide EEYPDR. The OP reactive tyrosines are located either
near the GTP binding site or within loops that interact laterally
with protofilaments. It is concluded that OP bind covalently to
tubulin, and that this binding could explain cognitive impairment
associated with OP exposure.
Gershon, S. & Shaw, F.H. (1961). Psychiatric sequelae of
chronic exposure to organophosphorus insecticides. Lancet.
1(7191), 1371-4.
Hong, Z.R., Hong, S.Y., Han, M.J., Lee, H.S., Gil, H.O., Yang, J.O.,
Lee, E.Y., & Hong, S.Y. (2008). Clinical observation of 12
farmers who believe themselves to have suffered from chronic
pesticide intoxication. Korean J Intern Med., 23(1), 1-4
BACKGROUND/AIM: We assessed twelve cases of suspected chronic
pesticide intoxication, with medically unexplained physical symptoms.
METHODS: Complete blood cell count (CBC), blood chemistry, routine
urinalysis, chest X-ray, ECG, gastrofiberscopy, abdominal
ultrasonography, neuroselective sensory nerve conduction threshold,
and psychological assessment were performed on 12 farmers who believe
themselves to have suffered from chronic pesticide intoxication.
RESULTS: No specific abnormalities were observed on CBC, routine
urinalysis, chest X-ray, ECG, gastroscopy, abdominal ultrasonography,
or peripheral nerve conduction velocity test. They persistently
manifested helplessness, depression, and anxiety. The results of both
psychological assessment and general physical examination revealed
the following clinical features: depression (8 cases), multiple
chemical hypersensitivity syndrome (2 cases), alcoholism (1 case),
and religious preoccupation (1 case). CONCLUSION: In those living in
the western rural area of South Korea, depression is a prominent
ongoing presentation in pesticide-exposed farmers, in addition to
unexplainable physical symptoms.
Jaga, K. & Dharmani, C. (2007). The interrelation between
organophosphate toxicity and the epidemiology of depression and
suicide. Rev Environ Health, 22(1), 57-73.
The literature on an association between organophosphate (OP)
toxicity and depression or suicide is scarce. An interrelation exists
among populations exposed to OPs, acute OP toxicity, neurobehavioral
effects, depression, suicide, and fatality. Acute OP toxicity is
characterized by the cholinergic syndrome with systemic and central
nervous system effects. Organophosphate-induced neurobehavioral
effects result in depression. A potential risk of depression and
suicide exists in farm workers exposed to OPs. The sociodemographics
of depression include age, gender, race, geographic region, social
factors, economics, psychiatric disorders, medical conditions, and
hereditary factors. Suicide is a major consequence of depression,
with multiple sociodemographic risk factors. Developing countries
have a higher incidence of OP toxicity, with limited information on
the prevalence of depression. In these countries, the incidence of
suicide is high, affecting more females. Suicide is more prevalent in
rural areas, and in farming communities, commonly with ingestion of
OPs. In industrialized countries, the incidence of OP toxicity is
lower, but the prevalence of depression is higher. Suicide rates are
lower in industrialized countries, affecting more males, the urban
population, and farming communities. Other lethal methods of suicide,
such as hanging, firearms, electrocution, and drug overdose are more
common in industrialized countries. A potential risk of depression or
suicide certainly exists from OP toxicity, largely depending on the
epidemiology or sociodemographics of these disorders. Scientific
evidence shows that the association between environmental toxicology
and psychiatry has important public health implications.
Joubert, J. & Joubert, P.H. (1988). Chorea and psychiatric
changes in organophosphate poisoning: A report of 2 further cases. SAMT.
74, 32-34.
The acute muscarinic and nicotinic side-effects of organophosphate
poisoning are well known. Less commonly encountered are neurological
symptoms such as chorea and psychiatric disturbances such as
psychoses and depression. Two patients with organophosphate poisoning
are described, both exhibiting marked choreiform dyskinesias and one
experiencing severe depression and emotional lability. Both responded
well to the appropriate treatment. Because of the widespread use of
organophosphate insecticides in agriculture, the neurological and
psychiatric effects of chronic lowdose exposure to organophosphates
in farmers and their employees deserves attention.
Link: http://196.33.159.102/1988%20VOL%20LXXIV%20Jul-Dec/Articles/07%20July/1.13%20CHOREA%20AND%20PSYCHIATRIC%20CHANGES%20IN%20ORGANOPHOSPHATE%20POISONING%20-%20A%20REPORT%20OF%202%20FURTHER%20CASES.%20J.pdf
Leo, R.J., Del Regno, P.A., Gregory, C., & Clark, K.L. (2001).
Insect repellant toxicity associated with psychosis. Psychosomtics,
42, 78-80.
Acute onset of atypical psychotic symptoms in a patient with no prior
psychiatric history necessitates evaluation for possible organic
etiologies. Clarification of the cause of an organic psychosis can be
quite puzzling in the absence of definitive neurologic symptoms,
metabolic abnormalities, sepsis, or obvious medication toxicity. We
report an unusual case of psychosis related to excess use of insect
repellents. Only two cases of comparable psychosis associated with
insect repellent use have been reported previously in the literature.
Link: http://psy.psychiatryonline.org/cgi/content/full/42/1/78
or http://psy.psychiatryonline.org/cgi/reprint/42/1/78.pdf
Levin, H.S., Rodnitzky, R.L., & Mick, D.L. (1976). Anxiety
associated with exposure to organophosphate compounds. Archives
of General Psychiatry, 33(2) 225-228.
Acute organophosphate poisoning is known to result in substantial
behavioral abnormalities. We assessed psychiatric manifestations of
exposure in workers less substantially exposed to organophosphate
compounds and showing no obvious signs of toxicity. Commercial
pesticide sprayers and farmers recently exposed to organophosphate
agents were compared to control subjects on personality tests, a
structured interview, and cholinesterase level.
The commercial sprayers but not the exposed farmers showed elevated
levels of anxiety and lower plasma cholinesterase than control
subjects. Assessment of other behavioral manifestations and red blood
cell cholinesterase failed to disclose other group differences. These
findings are viewed as tentative until confirmed by additional study,
but they point to the possibility that organophosphate compounds may
produce subtle defects in workers who are not obviously toxic. The
findings do not justify public alarm but do suggest an area
warranting more systematic and definitive investigation.
Roldan-Tapia, L., Leyva, A., Laynez, F., & Sanchez Santed, F.
(2005). Chronic neuropsychological sequelae of cholinesterase
inhibitors in the absence of structural brain damage: Two cases
of acute poisoning. Environmental Health Perspectives,
113, 762-766.
Here we describe two cases of carbamate poisoning. Patients AMF and
PVM were accidentally poisoned by cholinesterase inhibitors. The
medical diagnosis in both cases was overcholinergic syndrome, as
demonstrated by exposure to cholinesterase inhibitors. The widespread
use of cholinesterase inhibitors, especially as pesticides, produces
a great number of human poisoning events annually. The main known
neurotoxic effect of these substances is cholinesterase inhibition,
which causes cholinergic overstimulation. Once AMF and PVM had
recovered from acute intoxication, they were subjected to extensive
neuropsychological evaluation 3 and 12 months after the poisoning
event. These assessments point to a cognitive deficit in attention,
memory, perceptual, and motor domains 3 months after intoxication.
One year later these sequelae remained, even though the brain
magnetic resonance imaging (MRI) and computed tomography (CT) scans
were interpreted as being within normal limits. We present these
cases as examples of neuropsychological profiles of long-term
sequelae related to acute poisoning by cholinesterase inhibitor
pesticides and show the usefulness of neuropsychological assessment
in detecting central nervous system dysfunction in the absence of
biochemical or structural markers.
Link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1257603
or http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1257603&blobtype=pdf
Roldan-Tapia, L., Nieto-Escamez, F.A., Aguila, E.M., Laynez, F.,
Parron, T. & Sanchez-Santed, F. (2006). Neuropsychological
sequelae from acute poisoning and long-term exposure to carbamate and
organophosphate pesticides. Neurotoxicology and Teratology,
28, 694-703.
Abstract
This research examines the effects of different degrees of pesticide
exposure on neuropsychological performance. Exposures varied from
acute poisoning coupled with chronic exposure to low or high levels
of chronic exposure (defined by years of exposure). A cross-sectional
neuropsychological and biochemical study was conducted in greenhouse
farmers from southern Spain: data from 24 acutely poisoned workers
and 40 non-poisoned but chronically (low or high) exposed sprayers
were compared to 26 controls. We examined performance on 21
neuropsychological tests that assessed attention, memory, praxis,
gnosis, motor coordination, naming and reasoning and also examined
values of plasmatic cholinesterase. Results indicated statistically
significant neuropsychological deficits in the acute poisoning and
high chronic exposure groups after controlling for confounds, whereas
similar performance was seen in the low chronic exposed subjects and
controls. Subjects who were acutely poisoned performed worse than the
other groups on perceptual, visuomotor, visual memory and mood state
domains. Both the acutely poisoned and the chronically high exposed
subjects obtained significantly lower scores in the perceptual,
verbal memory and visuomotor domains. Levels of butyrylcholinesterase
were related to the seasonal sprayer activity except in the case of
acutely poisoned subjects. Conclusions: Both acutely poisoned
long-term workers and chronically high (N10 years) exposed workers
exhibited similar disturbances in perception and visuo-motor
processing, in the absence of any related acute effect of
butyrylcholinesterase inhibition. In the case of acutely poisoned
subjects, verbal and perceptive learning and recall and constructive
abilities were also impaired. These results point to the need for
follow-up studies to assess the possible sequelae of chronic and
acute exposure to pesticides and their interactions.
Rosenstock, L., Daniell, W., Barnhart, S., Schwartz, D., &
Demers, P.A. (1990/ published online 2007). Chronic
neuropsychological sequelae of occupational exposure to
organophosphate insecticides. American Journal of Industrial Medicine,
18 (3), 321-325.
The early (immediate and delayed) neurotoxic effects of acute
organophosphate intoxication are well documented in the scientific
literature; lack of recognition and inappropriate treatment of
occupational poisonings continue. Less well understood is the
potential development of chronic neuropsychological sequelae from
exposures to insecticides. We undertook two cohort studies to assess
chronic neuropsychologic effects of insecticide poisoning. Based, in
part, on our clinical evaluation of several patients, these studies
included: 1) a retrospective cohort study assessing function at least
1 year following moderate to severe poisonings among farm workers;
and 2) a prospective cohort study assessing neuropsychological
function before and after a season of organophosphate exposures among
pesticide applicators. A typical case description, the study design,
methodologic problems, and preliminary findings of these ongoing
studies are presented.
Salvi, R.M., Lara, D.R., Ghisolfi, E.S., Portela, L.V., Dias, R.D.,
& Souza, D.O. (2003). Neuropsychiatric evaluation in subjects
chronically exposed to organophosphate pesticides. Toxicological
Sciences, 72, 267-271.
Long-term exposure to low levels of organophosphate pesticides (OP)
may produce neuropsychiatric symptoms. We performed clinical,
neuropsychiatric, and laboratory evaluations of 37 workers involved
in family agriculture of tobacco from southern Brazil who had been
exposed to OP for 3 months, and in 25 of these workers, after 3
months without exposure to OP. Plasma acetylcholinesterase activity
levels of all subjects were within the normal range (3.2 to 9.0 U/l)
and were not different between on- and off-exposure periods (4.7
± 0.9 and 4.5 ± 1.1 U/l, respectively). Clinically
significant extrapyramidal symptoms were present in 12 of 25
subjects, which is unexpected in such a population. There was a
significant reduction of extrapyramidal symptoms after 3 months
without exposure to OP, but 10 subjects still had significant
parkinsonism. Mini-mental and word span scores were within the
expected range for this population and were not influenced by
exposure to OP. Eighteen of the 37 subjects (48%) had current
psychiatric diagnoses in the first interview (13 with generalized
anxiety disorder and 8 with major depression). Among the 25 subjects
who completed both evaluations, the total number of current
psychiatric diagnoses, after 3 months without using OP, dropped from
24 to 13 and the number of affected individuals with any psychiatric
diagnosis dropped from 11 to 7. In conclusion, this study reinforces
the need for parameters other than acetylcholinesterase activity to
monitor for chronic consequences of chronic low-dose OP exposure, and
it suggests that subjects have not only transient motor and
psychiatric consequences while exposed, but may also develop enduring
extrapyramidal symptoms.
Link: http://toxsci.oxfordjournals.org/cgi/content/full/72/2/267
or http://toxsci.oxfordjournals.org/cgi/reprint/72/2/267
Sanchez-Amate, M.C., Flores, P., & Sanchez-Santed, F. (2001).
Effects of chlorpyrifos in the plus maze model of anxiety. Behavoural
Pharmacology, 12(4), 285-292.
Abstract
The purpose of the present study was to determine the effect of two
different doses of the organophosphate insecticide O, O?-diethyl-O -3,5,6-trichloro-2-pyridylphosphorothionate
[chlorpyrifos (CPF)], a cholinesterase (ChE) inhibitor, in the
plus-maze test of anxiety in the rat, as well as on
acetylcholinesterase (AChE) activity in the brain. In a first
experiment, the behavioural methodology was validated by showing the
anxiolytic and anxiogenic effects of diazepam and pentylenetetrazole
(PTZ), respectively. Acute exposure to CPF (166?mg/kg and 250?mg/kg,
s.c.) produced significant dose-dependent inhibition (54% and 71%,
respectively) of whole-brain AChE 48 hours after treatment. Neither
dose produced signs of acute cholinergic toxicity at any time
following treatment, as was verified by a functional observational
battery. Both doses of CPF were injected 48?h before testing in the
plus-maze and were shown to have anxiogenic effects as demonstrated
by the significant decrease in the percentage of time spent and
percentage of entries into open arms. This report thus shows clear
behavioural alteration as an acute effect of an organophosphate in
the absence of any classic sign of cholinergic toxicity. Our results
are relevant to the understanding of both the pharmacology of anxiety
and the behavioural toxicology of cholinesterase inhibitors.
Slotkin, T.A., Ryde, I.T., Levin, E.D. & Seidler, F.J. (2008).
Developmental neurotoxicity of low dose diazinon exposure of neonatal
rates: Effects on serotonin systems in adolescence and
adulthood. Brain Research Bulletin, 75(5), 640-647.
Abstract
The developmental neurotoxicity of organophosphate pesticides targets
serotonin (5HT) systems, which are involved in emotional and
appetitive behaviors. We exposed neonatal rats to daily doses of
diazinon on postnatal days 1–4, using doses (0.5 or 2 mg/kg)
spanning the threshold for barely-detectable cholinesterase
inhibition. We then evaluated the effects on 5HT1A and 5HT2
receptors, and on the 5HT transporter in cerebral cortical regions
and the brainstem in adolescence through adulthood. Diazinon evoked a
lasting deficit in 5HT1A receptors in males only, whereas it caused a
small but significant increase in 5HT transporters in females;
neither effect showed a significant regional selectivity. This
pattern differed substantially from that seen in earlier work with
another organophosphate, chlorpyrifos, which at pharmacodynamically
similar doses spanning the threshold for cholinesterase inhibition,
evoked a much more substantial, global upregulation of 5HT receptor
expression; with chlorpyrifos, effects on receptors were seen in
females, albeit to a lesser extent than in males, and were also
regionally distinct. The effects of diazinon were nonmonotonic,
showing larger alterations at the lower dose, likely reflecting
positive trophic effects of cholinergic stimulation once the
threshold for cholinesterase inhibition is exceeded. Our results
reinforce the idea that different organophosphates have fundamentally
distinct effects on the developmental trajectories of specific
neurotransmitter systems, unrelated to their shared action as
cholinesterase inhibitors. The effects on 5HT circuits expand the
scope of behavioral endpoints that need to be considered in
evaluating the developmental neurotoxicity of organophosphates
[PDF available]
Stallones, L. & Beseler, C. (2002). Pesticide poisoning and
depressive symptoms among farm residents. Ann Epidemiol. 12, 389-394.
PURPOSE:
The purpose of the study presented is to evaluate the association
between pesticides and depressive symptoms among a population exposed
to chemicals as a result of agricultural use. Chronic sequelae of
acute pesticide poisoning from organophosphate compounds may include
anxiety and depression. In some states, farmers have been reported to
have higher rates of depression than other population groups. Little
work has been done to describe the effects of exposure to
organophosphate compounds and depressive symptoms among the farming population.
METHODS:
Data for this study came from a cross sectional survey of farmers and
their spouses conducted in an eight county area in northeastern
Colorado. Personal interviews were conducted with the study
participants. Depressive symptoms were assessed using the Center for
Epidemiologic Studies-Depression (CES-D) scale. Pesticides applied on
the farms were assessed using self-reported questionnaires.
Conditional logistic regression was used to model the relationship
between depression and pesticide-related illness in a stratified analysis.
RESULTS:
Between 1992-1997, 761 individuals were enrolled in this cross
sectional survey. Adjusting for a number of potential confounders,
the odds ratio for depression associated with pesticide-related
illness was 5.87 [95% confidence interval (CI) _2.56-13.44].
CONCLUSIONS:
Exposure to pesticides at a high enough concentration to cause self
reported poisoning symptoms was associated with high depressive s
symptoms independently of other known risk factors for depression
among farm residents.
Stoller, A., Krupinski, J., Christophers, A.J. & Blanks, G.K.
(1965). Organophosphorus insecticides and major mental illness: An
epidemiological investigation. Lancet. 285(7400), 1387-1388.
Timofeeva, O.A., Sanders, D., Seemann, K., Yang, L., Hermanson, D.,
Regenbogen, S., Agoos, S., Kallepalli, A., Rastogi, A., Braddy, D.,
Wells, C., Perraut, C., Seidler, F.J., Slotkin, T.A., & Levin, E.
(2008). Persistent behavioral alterations in rats neonatally exposed
to low doses of organophosphate pesticide, parathion. Brain
Research Bulletin, 77, 404-411.
Abrstract
Although developmental exposures of rats to low levels of the
organophosphate pesticides (OPs), chlorpyrifos (CPF) or diazinon
(DZN), both cause persistent neurobehavioral effects, there are
important differences in their neurotoxicity. The current study
extended investigation to parathion (PTN), an OP that has higher
systemic toxicity than either CPF or DZN. We gave PTN on postnatal
days (PND) 1–4 at doses spanning the threshold for systemic
toxicity (0, 0.1 or 0.2 mg/kg/day, s.c.) and performed a battery of
emotional and cognitive behavioral tests in adolescence through
adulthood. The higher PTN dose increased time spent on the open arms
and the number of center crossings in the plus maze, indicating
greater risktaking and overall activity. This group also showed a
decrease in tactile startle response without altering prepulse
inhibition, indicating a blunted acute sensorimotor reaction without
alteration in sensorimotor plasticity. T-maze spontaneous
alternation, novelty-suppressed feeding, preference for sweetened
chocolate milk, and locomotor activity were not significantly
affected by neonatal PTN exposure. During radial-arm maze
acquisition, rats given the lower PTN dose committed fewer errors
compared to controls and displayed lower sensitivity to the amnestic
effects of the NMDA receptor blocker, dizocilpine. No PTN effects
were observed with regard to the sensitivity to blockade of
muscarinic and nicotinic cholinergic receptors, or serotonin 5HT2
receptors. This study shows that neonatal PTN exposure evokes
long-term changes in behavior, but the effects are less severe, and
in some incidences opposite in nature, to those seen earlier for CPF
or DZN, findings consistent with our neurochemical studies showing
different patterns of effects and less neurotoxic damage with PTN.
Our results reinforce the conclusion that low dose exposure to
different OPs can have quite different neurotoxic effects, obviously
unconnected to their shared property as cholinesterase inhibitors.
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