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Is Toxoplasma Gondii Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-Representative Birth Cohort


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Background: Toxoplasma gondii (T. gondii) is a protozoan parasite present in around a third of the human population. Infected individuals are commonly asymptomatic, though recent reports have suggested that infection might influence aspects of the host's behavior. In particular, Toxoplasma infection has been linked to schizophrenia, suicide attempt, differences in aspects of personality and poorer neurocognitive performance. However, these studies are often conducted in clinical samples or convenience samples. Methods/results: In a population-representative birth-cohort of individuals tested for presence of antibodies to T. gondii (N = 837) we investigated the association between infection and four facets of human behavior: neuropsychiatric disorder (schizophrenia and major depression), poor impulse control (suicidal behavior and criminality), personality, and neurocognitive performance. Suicide attempt was marginally more frequent among individuals with T. gondii seropositivity (p = .06). Seropositive individuals also performed worse on one out of 14 measures of neuropsychological function. Conclusion: On the whole, there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment.
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Is Toxoplasma Gondii Infection Related to
Brain and Behavior Impairments in Humans?
Evidence from a Population-Representative
Birth Cohort
Karen Sugden
*, Terrie E. Moffitt
, Lauriane Pinto
, Richie Poulton
, Benjamin
S. Williams
, Avshalom Caspi
1Department of Psychology & Neuroscience, Duke University, Durham, North Carolina, United States of
America, 2Duke Center for Genomic & Computational Biology, Duke University, Durham, North Carolina,
United States of America, 3Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke
University, Durham, North Carolina, United States of America, 4Social, Genetic, and Developmental
Psychiatry Centre, Institute of Psychiatry, Kings College London, London, United Kingdom, 5Department of
Psychology, University of Otago, Dunedin, New Zealand
Toxoplasma gondii (T.gondii) is a protozoan parasite present in around a third of the human
population. Infected individuals are commonly asymptomatic, though recent reports have
suggested that infection might influence aspects of the hosts behavior. In particular, Toxo-
plasma infection has been linked to schizophrenia, suicide attempt, differences in aspects
of personality and poorer neurocognitive performance. However, these studies are often
conducted in clinical samples or convenience samples.
In a population-representative birth-cohort of individuals tested for presence of antibodies to
T.gondii (N = 837) we investigated the association between infection and four facets of
human behavior: neuropsychiatric disorder (schizophrenia and major depression), poor
impulse control (suicidal behavior and criminality), personality, and neurocognitive perfor-
mance. Suicide attempt was marginally more frequent among individuals with T.gondii
seropositivity (p= .06). Seropositive individuals also performed worse on one out of 14 mea-
sures of neuropsychological function.
On the whole, there was little evidence that T.gondii was related to increased risk of psychi-
atric disorder, poor impulse control, personality aberrations or neurocognitive impairment.
PLOS ONE | DOI:10.1371/journal.pone.0148435 February 17, 2016 1/14
Citation: Sugden K, Moffitt TE, Pinto L, Poulton R,
Williams BS, Caspi A (2016) Is Toxoplasma Gondii
Infection Related to Brain and Behavior Impairments
in Humans? Evidence from a Population-
Representative Birth Cohort. PLoS ONE 11(2):
e0148435. doi:10.1371/journal.pone.0148435
Editor: Herbert B. Tanowitz, Albert Einstein College
of Medicine, UNITED STATES
Received: June 17, 2015
Accepted: January 18, 2016
Published: February 17, 2016
Copyright: © 2016 Sugden et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
Data Availability Statement: Due to restrictions set
by the University of Otago IRB, data are available
upon request. Requests for the data may be made to
the corresponding author (
Funding: The Dunedin Multidisciplinary Health and
Development Research Unit is supported by the New
Zealand Health Research Council (http://www.hrc.; RP). This research received support from
US National Institute on Aging (NIA: https://www.nia. grants AG032282, AG048895 (AC and
TEM), and UK Medical Research Council (http://www. grant MR/K00381X (AC and TEM).
Toxoplasma gondii (T.gondii) is an obligate protozoan parasite of all warm-blooded mammals
including humans, where infection has been linked to schizophrenia, suicide attempt, differ-
ences in aspects of personality and poorer neurocognitive performance. In humans, the pri-
mary source of infection is through contact with the feces of infected animals, especially
domestic cats, the definitive host in which the T.gondii protozoan completes its life cycle.
Alternate sources of infection occur through contact and ingestion of infected meat (especially
pork), maternal-fetal transmission and exposure to soil and water contaminated with oocytes.
T.gondii is geographically omnipresent, and it is estimated that age-adjusted country-level
seroprevalence ranges from around 3% in South Korea to 76% in Costa Rica [1].
In rare cases, Toxoplasmosis can present with severe pathological symptoms, including reti-
nochoroiditis, myocarditis and meningoencephalitis, potentially leading to death [2]. However,
most infected humans are asymptomatic, exhibiting few or no physiological symptoms. Because
of this asymptomatic nature, it was long thought that latent T.gondii infection was of little pub-
lic health significance except in cases of concurrent immunosuppression, such as HIV infection.
However, recent reports have suggested that infection with T.gondii might have previously
unrecognized consequences in humans.
One such consequence concerns host behavioral manipulation. In terms of the relationship
between the intermediate and the definitive host, modifying normal interactions between the
two would be advantageous to the parasitestransmission and reproduction. In other words,
modification of a rodents normal aversive reaction to felines would be advantageous to the
parasite, since it would generate a higher chance of it being consumed by the cat, the organism
in which the parasites life cycle is completed [3]. Indeed, evidence exists that infection of mice
by T.gondii predicts innate loss of fear of cat urine [4] and impaired working memory [5].
These observations have led to the hypothesis that such manipulations might not be unique to
rodent hosts. As such, extrapolations of these phenomena to correlates of human behavior are
gaining attention.
In line with observed effects of infection on rodentsbehavior, most human research has
focused on behavioral domains involving psychiatric illness, impulsivity and aberrant neuro-
cognitive processes. The most heavily researched correlate of T.gondii infection is schizophre-
nia. Interestingly, some acute cases of T.gondii infection result in hallucinations, a key feature
of schizophrenia, and reports of inflated numbers of T.gondii positive individuals in samples
of psychiatric inpatients were made as early as the 1950s[
6]. The culmination of these findings
is a recent meta-analysis of 38 studies, which suggests that T.gondii infection increases the
odds of developing schizophrenia 2.7 times (OR, 2.71, 95%CI 1.933.80) [7]. In addition, links
with T.gondii have also been suggested with major depressive disorder; however, these sugges-
tions have been more hyperbolic. One case report demonstrated alleviation of depressive symp-
toms upon successful T.gondii treatment [8], whilst another reported a correlation between cat
bites and depression in women [9]. However, association studies of T.gondii infection with
depression have been inconsistent [10,11].
Poor impulse regulation, including violent and risk-taking behavior, is another potential
consequence of infection. Latent T.gondii infection has been associated with increased human
trait aggression in females and increased impulsivity in males [12]. Other studies have reported
links between T.gondii antibody titer and suicide attempt [1315]. Complementing these indi-
vidual-level studies, cross-national comparisons have documented that national seroprevalence
rates of T.gondii antibodies titers are positively correlated with higher nation-wide rates of
both suicide and homicide [1,16,17]. Yet another study has reported higher incidence in sero-
positivity amongst prison inmates compared to controls [18]. Further reports show that T.
Toxoplasma Gondii and Neuropsychological Outcomes
PLOS ONE | DOI:10.1371/journal.pone.0148435 February 17, 2016 2/14
Additional support was provided by the Jacobs
Foundation ( Jacobs
Prize 2010 (AC and TEM). The funders had no role in
study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Competing Interests: The authors have declared
that no competing interests exist.
gondii seropositivity is related to both fatal and non-fatal traffic road accidents [19,20], pre-
sumably reflecting poor impulse regulation.
Finally, there is some evidence that neurocognitive and personality differences exist between
seropositive and seronegative individuals. In particular, slower reaction times [21,22] and
poor attention [23] appear to be associated with T.gondii seropositivity, along with lower
scores of Novelty Seeking [24].
This study tested the hypothesis that T.gondii infection is related to impairment in brain
and behavior, as measured by a range of phenotypes encompassing neuropsychiatric disorders,
poor impulse control, personality and neurocognitive deficits. We tested the hypothesis in a
population-representative birth cohort of adults enrolled in the Dunedin Longitudinal Study.
We drew on data derived from psychiatric interviews, neuropsychological testing, and a search
of administrative records to conduct, to our knowledge, the most comprehensive evaluation to
date of the link between T.Gondii infection and the full panoply of presumptive impairments.
Materials and Methods
Participants are members of the Dunedin Multidisciplinary Health and Development Study, a
longitudinal investigation of health and behavior in a population-representative birth cohort
[25]. Study members (N = 1,037; 91% of eligible births; 52% male, 48% female) were all individ-
uals born between April 1972 and March 1973 in Dunedin, New Zealand, who were eligible for
the longitudinal study based on residence in the province at age 3 and who participated in the
first follow-up assessment at age 3. The cohort represents the full range of socioeconomic status
in the general population of New Zealands South Island and matches the NZ National Health
and Nutrition Survey on adult health indicators (e.g. BMI, smoking, GP visits)[26]. The major-
ity of cohort members are White. Assessments were carried out at ages 3, 5, 7, 9, 11, 13, 15, 18,
21, 26, 32, and most recently, 38 years, when we assessed 95% of the 1,007 study members who
were still alive. At each assessment wave, Study members (including emigrants and prisoners)
were brought to the Dunedin Multidisciplinary Health and Development Research Unit for a
full day of interviews and examinations. These data are supplemented by searches of official
records, and by questionnaires that were mailed to informants nominated by the Study mem-
bers themselves. Written informed consent was obtained from all Study members. The Univer-
sity of Otago Ethics Committee approved each phase of the Study and the consent procedure.
Blood collection and processing
Venous blood samples were collected from Study members at age 38 by a trained phlebotomist
using standard blood collection apparatus. Blood was collected into 10ml K
EDTA Vacutainer
tubes (BD, Franklin Lakes, NJ). After the necessary initial inversion, tubes were processed by
centrifugation at 2,000g for 10 minutes (K
EDTA) and the plasma fraction was transferred
into 2ml cryovials. All plasma was stored at -80°C until analysis.
T.gondii IgG level measurement
Levels of IgG antibodies to T.gondii were determined using a Toxoplasma IgG Immunosimpli-
city EIA kit (Diamedix, FL., USA). Briefly, plasma was diluted 1 in 100 in sample diluent prior
to assaying, and 100μL of diluted samples, standards (0 IU/ml, 50 IU/ml and 250IU/ml), con-
trols (high positive, low positive and negative) and blank (sample diluent only) were placed in
the reaction plate. Reactions were performed following the manufacturers instructions. All
EIA reactions were performed in duplicate. Upon completion of the reactions, OD readings at
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450nm (correcting for background at 600nm) were read using a Spectramax-384 spectropho-
tometer (Molecular Devices, Sunnydale, CA) and data acquired using SoftMax Pro software
(Molecular Devices). Raw OD units were transformed by subtracting the mean OD value of the
sample blank, and a standard curve was calculated using a point-point curve fit of the stan-
dards. The resulting equation was used to extrapolate sample OD values into IU/ml units.
These values were multiplied by the initial dilution factor (1 in 100) to derive an estimate of
plasma IU/ml. Duplicate values were then averaged to derive a mean IU/ml per sample. The
manufacturer-recommended cut-off value for seropositivity for anti-Toxoplasma IgG using
this EIA assay was 50 IU/ml, based on the WHO 3rd International Standard for Anti-Toxo-
plasma; Values above 50 IU/ml were designated positive for anti-Toxoplasma IgG; all other
values were designated negative. The mean within-assay coefficient of variation (%CV) was
Outcome measures
The measures used as outcome variables in this study are described in Table 1. Briefly, we
assessed four facets of human behavior: neuropsychiatric disorder (DSM diagnosis of schizo-
phrenia and depression), indicators of poor impulse control (non-suicidal self-injury,
attempted suicide, criminal convictions, and accident claims), Big-five personality traits
(Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism),
and neurocognitive performance (e.g., general intelligence, executive functions, memory, and
processing speed).
Statistical analysis
The association between T.gondii infection status and the various phenotypes were tested
using SPSS version 22 (IBM, New York, NY) and SAS (SAS Institute Inc., Cary, NC). We tested
associations between T.gondii infection and outcomes in a regression of the form: A=a+b1
(T.gondii)+b2(sex) + e, where Ais one of the 27 outcome measures. The form of regression
varied depending on whether the outcome under consideration represented binary or continu-
ous data.
Plasma samples were available for 837 individuals at age 38 (423 male, 50.4%). Of these indi-
viduals, 236 (28.2%) had T.gondii IgG antibodies above 50 UI/ml, indicating a positive T.
gondii infection status. This is similar to seroprevalence rates in other developed Western
countries [1]. Males (32.6%) were significantly more likely to test positive for T.gondii than
females (23.7%) (χ2(df) = 8.28(1), p<0.01). All subsequent inferential tests included a statisti-
cal control for sex. T.gondii infection status was not related to socioeconomic status (SES); pro-
portions of individuals testing positive for T.gondii IgG in low, medium and high SES groups
were 32.2%, 29.4% and 23.4%, respectively (χ2(df) = 4.41(1), p= 0.11). We compared people
with missing (N = 200) versus non-missing (N = 837) T.gondii seroprevalence data at age 38.
Seroprevalence data were missing because a) for cultural reasons, Maori-ancestry cohort mem-
bersblood was not studied (7% of cohort), b) Study members either did not consent to phle-
botomy (2%), did not take part at age-38 assessment (5%), or died before age 38 (3%), or c)
immunoassay data did not pass quality control (2%). Across all 27 outcome variables tested in
our analysis, we found only three differences: Study members with missing T.gondii data were
more likely to meet a diagnosis of schizophrenia (N = 13, 10.7%; OR (95% CI) = 4.07 (2.01
8.24), p<.01), a diagnosis of major depression (N = 28, 24.1%; OR (95% CI) = 1.77 (1.11
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Table 1. Brief description of neuropsychiatric, impulse control, personality and neurocognitive outcome measures used in the study.
Outcome measure Description
Neuropsychiatric disorders
Schizophrenia Our assessment of schizophrenia has been previously described [27]. Briey, schizophrenia was assessed with
the Diagnostic Interview Schedule (DIS) following the Diagnostic and Statistical Manual of Mental Disorders
(DSM). Diagnoses required hallucinations (which are not substance use-related) in addition to at least two other
positive symptoms. In addition, objective evidence of impairment resulting from psychosis was required, as
reported by informants and as recorded in the Studys life-history calendars.
Major depression Depression was diagnosed at age 38 using the DIS following diagnostic criteria for the DSM-IV. The reporting
period was the past year.
Indicators of Poor Impulse Control
Non-suicidal self-injury Self-reported engagement in self-injury behaviors (e.g., cutting wrists, burning self) since assessment at age 32
were ascertained at age 38 during standardized clinical interviews as well as via the Life History Calendar [28].
Behaviors only counted as non-suicidal self-injury if not accompanied by the intent to die.
Attempted suicide Self-reported suicide attempt(s) since assessment at age 32 were ascertained during standardized clinical
interviews at age 38 as well as via the Life History Calendar [28]. Examples of behaviors considered attempted
suicide include cutting or stabbing oneself, overdosing on pills, attempting to hang or strangle oneself, or
attempting to drown. Behaviors counted as attempted suicide only if accompanied by self-reported intent to die.
Criminal conviction Linked New Zealand (NZ) government records (via the New Zealand Police) were used to determine whether
Study members were convicted of any crime in adulthood, including property (e.g., theft of property of value
greater than $500, receipt of stolen property, burglary, breaking and entering, shoplifting, credit car theft), court
order violations (e.g., obstructing or resisting police, breaching parole, escaping prison, misleading welfare
ofcer, failing to pay nes, failing to answer summons), drugs (e.g., possessing drug paraphernalia, supplying or
procuring hard drugs or prescription medications, selling cannabis), violence (e.g., aggravated cruelty to animal,
common assault, assault with intent to injure with weapon, assault of police ofcer, robbery, robbery aggravated
with rearm, manslaughter, rape, common assault domestic) and driving convictions (including excess blood
alcohol, speeding, driving without a license, causing injury, hit and run, but not including trafc infringements).
Accident claims The number of accepted accident claims per Study member from ages 21 to 38 were determined via the New
Zealand Accident Compensation Corporation (ACC). The ACC provides comprehensive, no-fault personal injury
coverage for all residents and visitors in New Zealand.
Personality at age 38
At age 38, Study members nominated people "who knew them well." These informants were mailed
questionnaires and asked to describe each Study member using a 25-item version of the Big Five Inventory
measuring the personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and
Openness to Experience.
Description of a Typical High Scorer Description of a Typical Low Scorer
Openness to experience Imaginative, creative, aesthetically sensitive,
quick to learn, clever, insightful, attentive and
aware of feelings
Resistant to change, conventional, prefers the plain,
straightforward, and routine over the complex, subtle, and
Conscientiousness Responsible, attentive, careful, persistent,
orderly, planful, and future-oriented
Irresponsible, unreliable, careless, distractible, and
Extraversion Outgoing, expressive, energetic, dominant Quiet, lethargic, content to follow otherslead
Agreeableness Cooperative, considerate, empathic, generous,
polite, and kind
Aggressive, rude, spiteful, stubborn, cynical, and
Neuroticism Anxious, vulnerable to stress, guilt-prone,
lacking in condence, moody, angry, easily
frustrated, and insecure in relationships
Emotionally stable, adaptable, and sturdy
Neurocognition at age 38
Domain Tested Description
Wechsler Adult Intelligence Scale
The WAIS-IV [29] was administered to Study members
individually according to standard protocol at age 38 years.
IQ at 38 General Intelligence Derived from ten subtests using the method recommended
in the test manual.
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Table 1. (Continued)
Verbal comprehension Verbal Comprehension Verbal Comprehension Index comprises the Information,
Similarities, and Vocabulary subtests. The Information
subtest is a test of general knowledge and reects the ability
to acquire and store knowledge in long-term memory, to
access it, and to express it verbally. The Similarities subtest
is a test of verbal concept formation, abstraction, and
reasoning. It captures the ability to categorize and
conceptualize information available in long-term memory.
The Vocabulary subset is a test of language skills and
includes questions about the meaning of words (e.g., What
does winter mean?). It captures language processes such
as the ability to acquire word meaning, recall it, and
effectively express it.
Perceptual reasoning Perceptual reasoning Perceptual Reasoning Index comprises the Block Design,
Picture Completion, and Matrix Reasoning subtests. The
Block Design subtest is a test of visual-spatial organization,
executive planning, and problem solving skills. The test
requires putting together two, four, or nine red and white
blocks in a pattern according to specic designs being
displayed. The Picture Completion subtest is a test of visual
discrimination and reasoning. The test involves looking at an
incomplete picture of common objects or scenes and
determining which part is missing. Test items are arranged
in order of difculty and have time limits. The Matrix
Reasoning subtest is a test of visual-perceptual organization
and reasoning ability. The test requires viewing design
patterns with a missing part and selecting, from a set of ve
options, the part that completes the design.
Working memory Working memory Working Memory Index comprises the Arithmetic and Digit
Span subtests. The Arithmetic subtest is a test that requires
working memory processes to be applied to orally-presented
verbal information. It involves numerical knowledge, short-
term memory, attention, and concentration. Arithmetic
problems are presented in story format (e.g., Four men can
nish a job in eight hours. How many men will be needed to
nish it in one-half hour?). Performance requires holding
information in short-term memory, accessing long-term
memory to retrieve numerical rules of mathematical
operation, and using the rules to manipulate the stored data.
The Digit Span subtest is a test of memory span, attention/
concentration, and ability to mentally manipulate information.
The test requires listening to a sequence of digits read aloud
and repeating them in forward, backward, and ascending
Processing speed Processing speed Processing Speed Index comprises the Digit Symbol Coding
and Symbol Search subtests. The Digit Symbol Coding
subtest is a test of processing speed, psychomotor speed
and coordination, and attention/concentration. Better
performance also depends on incidental learning. A key that
pairs symbols and numbers is presented. The test requires
lling in rows containing blank squares (each with a
randomly assigned number above it) using the key. The
Symbol Search subtest is a test of visual processing speed,
psychomotor speed and attention/ concentration. Better
performance also depends on incidental learning. The test
requires determining whether target symbols appear in a
row of symbols.
Trail Making Test B time Executive Functions Test of scanning and tracking, divided attention, and mental
exibility [30]. The test involves drawing lines to connect
consecutively numbered and lettered circles, alternating
between numbers and letters. Scores represent the time, in
seconds, to complete the test.
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Table 1. (Continued)
The Cambridge
Neuropsychological Test Automated
Battery (CANTAB)
The CANTAB [31] is a computerized test battery of
neuropsychological functioning that uses touch-screen
technology. The tests for the CANTAB have been selected
based on validation in primate/rodent models and/or
neuroimaging paradigms.
Rapid Visual Information
Processing: A Prime
Executive Functions Measure of sustained attention and vigilance. A white
box appears in the center of the computer screen, inside
which digits, from 2 to 9, appear in a pseudo-random order,
at the rate of 100 digits per minute. Subjects are requested
to detect target sequences of digits (for example, 2-4-6, 3-5-
7, 4-6-8) and to register responses using the press pad. The
signal detection measure of sensitivity to the target,
regardless of response tendency (range 0.00 to 1.00; bad to
good), is a measure of how good the subject is at detecting
target sequences using "Probability of Hit" and "Probability
of False Alarm."
Reaction Time: 5-choice Reaction
Motor Test Test of processing speed. The task is divided into ve
stages, which require increasingly complex chains of
responses. In each case, the subject must react as soon as
a yellow dot appears. The subject must respond by lifting
their nger from the press-pad and touching the yellow dot
on the screen. In some stages the dot may appear in one of
ve locations. The speed with which the subject releases the
press pad button in response to a stimulus in any one of ve
randomly presented locations. Choice reaction time latency,
averaged across all correct trials, is measured in
milliseconds and tends toward a positive skew.
Visual Paired Associates Learning:
Total errors, adjusted
Memory Test of visual memory and new learning. Boxes are
displayed on the screen and are opened in a random order.
One or more of them will contain a pattern. The patterns are
then displayed in the middle of the screen, one at a time,
and the subject must touch the box where the pattern was
originally located. If the subject makes an error, the patterns
are re -presented to remind the subject of their locations.
The difculty level increases through the test. The number of
patterns increases across eight stages (i.e., two 1 -pattern
stage s, two 2 -pattern stages, two 3 -pattern stages, one 6
-pattern stage, one 8 -pattern stage), which challenges even
very able subjects. For each stage, up to 10 trials are
presented until all the patterns are located correctly. Score is
the total number of errors (with an adjustment for each stage
not attempted due to previous failure).
Rey Auditory Verbal Learning Test Test of verbal learning and memory [32]. The test involves a
ve-trial presentation of a 15- word list and a one-time
presentation of an interference list.
Total Recall Memory The total number of words (060) recalled over four trials
(the sum of words recalled across trials 14).
Delayed recall Memory The total number of words (015) recalled after a 2530
minute delay.
Wechsler Memory Scale-III
The WMS-III [33] was administered individually according to
standard protocol.
Mental Control Executive Functions Test of attention and tracking. It requires reciting the months
of the year in backwards order, starting with December.
Responses were scored according to the instructions in the
WMS-III manual. Scores ranged from 1 (poor performance)
to 5 (good performance) and reect both accuracy and
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2.83), p= .02), and were more likely to have an adult criminal conviction (N = 54, 39.1%; OR
(95% CI) = 1.60 (1.042.46), p= .03).
1. Is T.gondii infection status related to neuropsychiatric conditions?
We tested whether T.gondii seropositivity was associated with increased prevalence of two
neuropsychiatric disorders; schizophrenia and major depression. T.gondii seropositivity was
not significantly associated to either of these conditions (Table 2).
2. Is T.gondii infection status related to poor impulse control?
We tested whether T.gondii seropositivity was associated with poor impulse control, as
reflected in four phenotypes: non-suicidal self-injury, suicide attempt, criminal convictions,
and traffic-related offences and accidents. T.gondii was not significantly associated with non-
suicidal self-injury, but there was a suggestive link between latent infection and suicide attempt
(Table 2). In regards to criminal behavior, there was no significant association between T.gon-
dii seropositivity and criminal convictions, as reflected in official conviction records (Table 2).
We further probed this non-significant association by testing whether T.gondii seropositivity
was linked to certain types of criminal offenses (e.g., violence, driving) that have been previ-
ously examined in studies of T.gondii infection. T.gondii seropositivity was not significantly
associated with increased risk of any type of criminal offending (Table 2).
3. Is T.gondii infection status related to personality differences?
In order to summarize the possible psychological differences that are associated with infection
by T.gondii, we examined the personality profiles of individuals who tested positive versus neg-
ative for T.gondii antibodies. To do this, we measured the Five-Factor Model of personality.
The past two decades have led to a consensus among psychologists that personality differences
can be organized along five broad dimensions: Openness to Experience, Conscientiousness,
Extraversion, Agreeableness, and Neuroticism [34]. Table 2 describes the mean scores across
all traits for seropositive and seronegative individuals. The personality profiles of individuals
who tested positive for T.gondii antibodies were indistinguishable from the personality profiles
of individuals who tested negative.
4. Is T.gondii infection status related to poorer neurocognitive
Lastly, we assessed the relationship between T.gondii seropositivity and a comprehensive
range of neurocognitive functions at age 38 (Table 3). We tested whether performance on the
WAIS-IV test of general intelligence at age 38 was associated with T.gondii seropositivity.
Table 1. (Continued)
Paired associates: Total Recall Memory Test of verbal learning and memory. Eight pairs of unrelated
words (e.g., truck-arrow) are read aloud and followed by a
recall task (one of the words from each word pair is given,
and the associated word must be recalled). Four trials of the
eight word-pairs are presented. Presentation of the word-
pairs is randomized across trials. The total recall score
represents the total number of words (032) recalled across
four trials.
Paired associates: Delayed Recall Memory The delayed recall score represents the total number of
words (08) recalled after a 2535 minute delay.
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There were no significant IQ differences between seropositive versus seronegative individuals.
We then tested whether T.gondii seropositivity was associated with poorer performance on a
range of functions encompassing verbal comprehension, perceptual reasoning, working mem-
ory, processing speed, executive functioning, motor functions and memory. T.gondii infection
status was associated with poorer memory performance on the Rey Auditory Verbal Learning
test. Associations between T.gondii infection status and all other tests of neurocognitive func-
tions were not significant.
Our results suggest that a positive test for T.gondii antibodies does not result in increased sus-
ceptibility to neuropsychiatric disorders, poor impulse control or impaired neurocognitive
ability. Moreover, we found no association between seropositivity and aberrant personality
Some traits which have been linked previously to T.gondii seropositivity were marginally
associated in our cohort. For example, we found that recently-attempted suicide was more
common in seropositive individuals. This trend is consistent with previous studies, where his-
tory of suicide attempt, but not completion, has been related to both antibody titer [13] and
seropositivity [15]. Similarly, our seropositive individuals performed more poorly on one test
Table 2. The association between T.gondii infection status and the range of neuropsychiatric disorders, indicators of poor impulse control and
Outcome measure T.gondii positive T.gondii negative Test statistic pvalue Effect Size (Cohensd
(N = 236) (N = 601) (V
N (%) N (%) Odds Ratio (95% CI)
Neuropsychiatric disorders
Schizophrenia 8 (3.4) 16 (2.7) 1.31 (0.553.12) .54 .06 (0.01)
Major depression 35 (14.8) 92 (15.4) 1.01 (0.661.54) .98 .00 (0.00)
Impulsive behavior
Non-suicidal self-injury 10 (4.3) 19 (3.2) 1.44 (0.663.16) .36 .09 (0.01)
Suicide attempt 8 (3.4) 8 (1.3) 2.63 (0.977.14) .06 .23 (0.01)
Crime and accidents*
Criminal conviction 70 (29.7) 136 (22.7) 1.19 (0.821.71) .36 .04 (0.00)
Violent criminal conviction 28 (11.9) 46 (7.7) 1.36 (0.812.29) .25 .07 (0.00)
Driving conviction 51 (21.6) 89 (14.9) 1.30 (0.861.96) .22 .06 (0.00)
M (SD) M (SD) est
Number of Accident claims** 7.01 (6.73) 6.46 (7.59) 0.00 .99
Personality,assessed at age 38 EMM (95% CI) EMM (95% CI) F.00 (0.00)
Openness to experience -0.04 (-0.170.09) 0.02 (-0.060.10) 0.62 .43 .06 (0.01)
Conscientiousness 0.01 (-0.120.14) 0.03 (-0.050.11) 0.07 .79 .02 (0.01)
Extroversion 0.00 (-0.130.13) 0.04 (-0.040.12) 0.31 .58 .04 (0.01)
Agreeableness -0.03 (-0.160.09) 0.04 (-0.040.12) 0.82 .36 .07 (0.01)
Neuroticism -0.01 (-0.140.16) -0.01 (-0.080.08) 0.01 .93 .01 (0.01)
All tests are controlled for sex. N (%) represents the number and percent of individuals within each seropositivity group presenting with each phenotype.
Personality scores are standardized to Mean = 0 and Standard Deviation = 1.
*Criminal conviction and accident claim data are controlled for amount of time spent in New Zealand.
**Differences tested using a zero-inated negative binomial model;
M (SD) = mean number (standard deviation) of accepted claims. EMM = Estimated Marginal Mean. 95% CI = 95% Condence Interval. V
= Variance of
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PLOS ONE | DOI:10.1371/journal.pone.0148435 February 17, 2016 9/14
of verbal learning and memory (the Rey Auditory Verbal Learning Test), but this finding was
the only significant difference among 14 tests and may have emerged by chance, since it was
not evident on other tests of memory (the CANTAB visual paired associates and the Wechsler
Memory Scale Paired Associates).
In contrast to previous studies, we did not observe a significant association between T.gon-
dii seropositivity and schizophrenia. Approximately 40 reports have now been published show-
ing links between schizophrenia and/or psychotic symptoms and infection status, leading to
the suggestion that psychosis-spectrum conditions are a consequence of infection. Biological
pathways have been proposed and pursued, centering on the schizophrenia-linked candidate
neurotransmitter dopamine; in rodents, infection with T.gondii leads to aberrant dopamine
signaling [35] and reduced expression of genes within the dopamine pathway, such as DRD1,
Table 3. The association between T.gondii infection status and neurocognitive function.
Outcome measure Domain T.gondii positive T.gondii negative Test
pvalue Effect Size
EMM (95% CI) EMM (95% CI) F
IQ at 38 General
2.40 .12 .12
Verbal comprehension Verbal
1.50 .22 .09
Perceptual reasoning Perceptual
2.16 .14 .11
Working memory Working memory 98.97
2.00 .16 .11
Processing speed Processing speed 99.43
1.03 .31 .08
Trail Making Test B time Executive
64.73 (62.0367.43) 63.96 (62.3065.62) 0.23 .63 .04
Mental Control Executive
2.97 (2.803.15) 3.12 (3.013.23) 2.02 .16 .11
Rapid Visual Information Processing:
A Prime
0.91 (0.900.92) 0.91 (0.910.92) 0.92 .34 .07
Reaction Time: 5-choice Reaction
Motor Test 327.72
0.35 .55 .05
Visual Paired Associates Learning:
Total errors, adjusted
Memory 11.85 (9.4614.25) 12.93 (11.4614.41) 0.57 .45 .06
Rey Auditory Verbal Learning Test
Total Recall Memory 36.76 (35.7637.76) 37.90 (37.2938.52) 3.64 .06 .15
Delayed recall Memory 8.83 (8.439.23) 9.33 (9.089.58) 4.38 .04 .16
Paired associates: Total Recall Memory 15.63 (14.5316.74) 16.32 (15.6417.01) 1.07 .30 .08
Paired associates: Delayed Recall Memory 5.09 (4.765.42) 5.28 (5.075.48) 0.89 .35 .07
All tests are controlled for sex. WAIS-IV tests are standardized to Mean = 100 and Standard Deviation = 15. EMM = Estimated Marginal Mean. 95%
CI = 95% Condence Interval.
= 0.01
Toxoplasma Gondii and Neuropsychological Outcomes
PLOS ONE | DOI:10.1371/journal.pone.0148435 February 17, 2016 10 / 14
DRD5 and MAOA [36]. However, we found no link to schizophrenia or its associated neuro-
psychological deficits in our cohort.
One explanation is that our failure to detect statistically significant associations between
T.gondii infection and brain and behavior impairments represents a false negative in an accu-
mulating evidence base. False negative findings arise for a number of reasons, including low
statistical power to detect associations due to small sample sizes (especially in relation to
schizophrenia). In our case, the possibility of false negatives needs to be evaluated against sev-
eral strengths of our study design. First, this is, to our knowledge, the most comprehensive
assessment of the possible link between T.gondii infection and a variety of impairments in a
single cohort. Previous positive associations have been reported across different studies, often
in selected or clinical samples; for example, one study will examine the link to violence, another
the link to schizophrenia, and yet another the link to self-injury, and so forth. Given that many
of these impairments are correlated in the population and are characterized by comorbid pre-
sentation, it would be expected that they should be detectable through deep and comprehensive
phenotyping of the same individuals drawn from a single birth cohort. Second, although our
cohort is of only modest size, it is adequately powered to detect small effect sizes (r= 0.1).
Moreover, we have previously published positive findings in this cohort using these same brain
and behavior phenotypes [27,28,37,38]. Third, our phenotypic assessment encompasses mul-
tiple sources including administrative records, reliable clinical interviews, well-established
personality measures and standardized neurocognitive assessments, and failure to detect asso-
ciations cannot be attributable to unreliable or idiosyncratic measurement practices. Fourth,
we have minimized unwanted heterogeneity by studying participants who are the same chro-
nological age. It is generally accepted that rates of infection increase as individuals age, proba-
bly due to cumulative increases in exposure opportunities [39]. By testing our hypotheses in a
cohort of same-aged individuals, we were able to reduce the chance of spurious associations
deriving from age-related exposure differences.
We do note two disadvantages of our study. First, T.gondii antibody status was assessed at
age 38 only. We were unable to correlate the timing of acquisition of infection with subsequent
changes in behavior. This is a limitation of all studies restricted to analysis of behavioral corre-
lates post-infection, the current study included. Since infection might have influences on brain
development (e.g. [40,41]) there might developmentally-sensitive periods where effects of
infection are magnified. It would be of great interest to conduct a similar investigation in a
cohort of younger individuals who can be tracked longitudinally in order to determine cause
and effect of the infection-behavior relationship. Disproportionate sample attrition can be a
confounder in association studies, although often study design limits the ability to test and doc-
ument missingness. We found evidence of selective missing data for three of our 27 outcome
variables; although this observation would be expected by chance, it is still a consideration. A
further consideration for all studies of T.gondii and behavioral outcomes, the present study
included, is variation of both the parasite and host and the relationship to pathogenicity. There
are a number of different T.gondii strains which differ in both virulence and prevalence across
populations [1]. Human genetic variation, especially within the major histocompatibility com-
plex, appears to be involved in pathogenicity of T.gondii [42]. Given these observations, some
potentially interesting future directions for studies of T.gondii infection correlates are inclusion
of measures of T.gondii strain and host response to infection (for example, magnitude of
response to parasite antigens). This addition is necessary in order to determine whether dis-
crepancies between reports can be ascribed to population-specific human and/or T.gondii
A second explanation of our null findings is that earlier reports of links between T.gondii
infection and behavioral impairments are exaggerated. Interest in the role of external organisms
Toxoplasma Gondii and Neuropsychological Outcomes
PLOS ONE | DOI:10.1371/journal.pone.0148435 February 17, 2016 11 / 14
influencing human psychiatric and cognitive health is currently high. This is, in part, due to an
increasing recognition of the role that inflammatory processes play in brain integrity [4345],
and in part due to the frustrating scientific search for biological causes with large effects in com-
mon mental disorders and processes (e.g. [46,47]). Interest in T.gondii in particular has not
only captured the imagination of researchers, but also the lay public. T.gondii is a microorgan-
ism whose source of transmission is common and relatable, as evidenced by numerous recent
popular opinion pieces (e.g., How Your Cat Is Making You Crazy,[
48]). It has been observed
that the hotterthe topic and as more studies are reported and accumulate, replication becomes
more difficult [49]. If we accept that the findings reported in the present article represent sce-
nario two, then views of the link between T.gondii and aberrant behavior may need to be tem-
pered accordingly.
In conclusion, our data do not support the hypothesis that infection by T.gondii is related to
negative behavioral outcomes in a population-representative cohort of early middle-aged indi-
viduals. In the presence of conflicting reports, better research designs are needed to fully estab-
lish the extent to which T.gondii influences impairments in brain and behavior phenotypes.
We thank the Dunedin Study members, Dunedin Unit research staff, and Study founder Phil
Author Contributions
Conceived and designed the experiments: KS TEM AC. Performed the experiments: KS LP
BSW. Analyzed the data: KS. Contributed reagents/materials/analysis tools: TEM RP AC.
Wrote the paper: KS AC.
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Toxoplasma Gondii and Neuropsychological Outcomes
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... When sporulated oocytes are ingested by the intermediate host, tissue cysts containing hundreds of bradyzoites can be formed in the various organs, including skeletal muscle, brain, and heart (Weiss and Kim, 2014;Armand et al., 2016). Complications of Toxoplasmosis in humans include abortion, eye problems, hydrocephalus, mental retardation, neurological problems, and, schizophrenia (Robert-Gangneux and Dard, 2012;Sugden et al., 2016). Consumption of raw or undercooked meat is a significant risk factor for T. gondii infection in humans (Jones et al., 2009). ...
Full-text available
Toxoplasma gondii is one of the most common zoonotic parasites worldwide. Among livestock, sheep have a higher prevalence of T. gondii infection. Toxoplasmosis causes abortion in sheep and has a high economic impact on sheep breeding. Human infection mainly occurs by eating undercooked or raw meat containing tissue cysts. The present study was conducted to determine the prevalence of T. gondii in the sheep slaughtered at the Malekan slaughterhouse. Of 300 sheep, 63 (21%) were serologically positive for anti-Toxoplasma antibodies. Of 133 male and 167 female sheep, the infection rates were determined as 17.29% and 23.95%, respectively. The sheep were divided into three age groups: 1-2, 2-3, and over three years old, with infection rates of 23.26%, 19.02%, and 26.66%, respectively. There was no significant relationship between the age and sex of sheep with the prevalence of T. gondii. This study shows that sheep are an important source of T. gondii. Since sheep are an important animal to produce livestock production such as meat in the region, it is suggested to consume meat after it is fully cooked to prevent and reduce infection. It is recommended that more studies should be conducted to compare the results obtained with the method used in this study with other serological and molecular methods.
... Brazilian Journal of Health Review, Curitiba, v. 6, n. 5, p. 25933-25945, sep./oct., 2023 infecção adquirida durante a internação hospitalar (ou seja, após 48 horas de internação) ou então relacionada a algum procedimento realizado no hospital (por exemplo, cirurgias), podendo manifestar-se inclusive após a alta17,21 .No final do ano de 2019 o mundo foi surpreendido por uma pandemia causada pelo vírus SARS-CoV-2 na cidade de Wuhan, na China. A infecção causada por este vírus denominou-se Covid-19 a qual atingiu mais de 27 milhões de pessoas em todo mundo até o momento, tornando-se assim um dos maiores desafios sanitários da atualidade 18 . ...
As infecções adquiridas dentro do ambiente hospitalar são consideradas as mais importantes complicações ocorridas em pacientes hospitalizados. Fazer um relato de caso de um paciente que convive com o vírus do HIV coinfectado por toxoplasmose neural e Covid-19 em ambiente de internação. Trata-se de uma pesquisa retrospectiva de caráter descritivo com abordagem quantitativa. Deu entrada W.C.L.F, 38 anos, masculino, com história de cefaleia halo craniana, náuseas e vômitos, evoluindo com confusão mental e desorientação. Tomografia computadorizada de crâneo mostrou lesão hipodensa subcortical em ambos os hemisférios cerebrais com edema compatível com infecção por toxoplasmose. Nos dias subsequentes a internação apresentou febre, dispneia e tosse. Realizado teste rápido e PCR para Covid 19 com resultados positivos. Colocado em isolamento para pacientes de SARS COV2. Horas depois, paciente apresentou melena franca e dispneia. Transferido para a UTI com quadro de sonolência, desorientação, pouco colaborativo, com tiragem intercostal. Paciente evoluindo com piora do quadro respiratório e após 24h de cuidados intensivos entrou em parada cardiorrespiratória-PCR. Realizado manobras de reanimação, mas sem sucesso. Paciente evoluiu para óbito. A prática do controle das infecções hospitalares são disciplinas dinâmicas que estão sofrendo evolução constante pois a prevenção das infecções hospitalares deve constituir o objetivo de todos os profissionais de saúde.
... In the past years, studies have been suggesting a possible connection between chronic T. gondii infection identified by positive serology with development of neuropsychiatric conditions (Flegr and Horácek 2020;Pastolache et al., 2021), such as suicidal attempts (Bak et al., 2018;Alvarado-Esquivel et al., 2021a), anxiety (Bay-Richter et al., 2019), depression (Shiadeh et al., 2016;Nasirpour et al., 2020;Alvarado-Esquivel et al., 2021b) and schizophrenia (Al-Hussainy et al., 2015;Esshili et al., 2016;Contopoulos-Ioannidis et al., 2022). However, conflicting studies highlight the absence of significant connections between chronic infection and the occurrence of these behavioural and/or neurological disorders (Gale et al., 2014;Sugden et al., 2016;Chegeni et al., 2019;Bles et al., 2021;Ademe et al., 2022). ...
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Toxoplasma gondii chronic infection is characterized by the establishment of tissue cysts in the brain and increased levels of IFN-γ, which can lead to brain circuitry interference and consequently abnormal behaviour in mice. In this sense, the study presented here sought to investigate the impact of chronic infection by two T. gondii strains in the brain of infection-resistant mice, as a model for studying the involvement of chronic neuroinflammation with the development of behavioural alterations. For that, male BALB/c mice were divided into three groups: non-infected (Ni), infected with T. gondii ME49 clonal strain (ME49), and infected with TgCkBrRN2 atypical strain (CK2). Mice were monitored for 60 days to establish the chronic infection and then submitted to behavioural assessment. The enzyme-linked immunosorbent assay was used for measurement of specific IgG in the blood and levels of inflammatory cytokines and neurotrophic factors in the brain, and the cell's immunophenotype was determined by multiparametric flow cytometry. Mice infected with ME49 clonal strain displayed hyperlocomotor activity and memory deficit, although no signs of depressive- and/or anxiety-like behaviour were detected; on the other hand, chronic infection with CK2 atypical strain induced anxiety- and depressive-like behaviour. During chronic infection by CK2 atypical strain, mice displayed a higher number of T. gondii brain tissue cysts and inflammatory infiltrate, composed mainly of CD3+ T lymphocytes and Ly6Chi inflammatory monocytes, compared to mice infected with the ME49 clonal strain. Infected mice presented a marked decrease of microglia population compared to non-infected group. Chronic infection with CK2 strain produced elevated levels of IFN-γ and TNF-ɑ in the brain, decreased NGF levels in the prefrontal cortex and striatum, and altered levels of fractalkine (CX3CL1) in the prefrontal cortex and hippocampus. The persistent inflammation and the disturbance in the cerebral homeostasis may contribute to altered behaviour in mice, as the levels of IFN-γ were shown to be correlated with the behavioural parameters assessed here. Considering the high incidence and life-long persistence of T. gondii infection, this approach can be considered a suitable model for studying the impact of chronic infections in the brain and how it impacts in behavioural responses.
... A 2016 study on a birth cohort of 1000 individuals found no evidence supporting the theory linking toxoplasmosis to an increased risk of psychiatric disorder, poor impulse control, personality aberrations, or neurocognitive impairment. Although the authors did not investigate cats' influence, they mentioned a popular opinion piece called "Your cat is driving you crazy!" and suggested that the theory may have originated from researchers' desire to find external explanations for the lack of biological causes that explain common mental disorders and processes [49]. In any case, the only notifiable form of the disease is congenital toxoplasmosis. ...
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Simple Summary Homeless cats pose a significant problem in Europe as they tend to congregate in urban areas where they can find food and shelter. Over time, they may then spread out into natural habitats. Animal welfare organizations provide care to these free-roaming cats, but some stakeholders call for capturing or sacrificing them, which is often illegal and ineffective. Spanish veterinarians urge for a sustainable approach to decrease the population of free-roaming cats through trap–neuter–return (TNR) programs and social awareness, rejecting lethal control and removal methods. A comprehensive study is required to evaluate their actual impact, and effective control programs should focus on non-lethal methods such as TNR and adoption. Public education on sterilization and identification is also needed to prevent abandonment. Abstract Homeless cats are a major problem in Europe, with hundreds of thousands abandoned every year. While many die, others can adapt to a lifestyle of roaming freely and establish community cat populations that tend to cluster together in groups. These groups of cats are typically found in urban areas that offer food and shelter to the cats. Animal welfare organizations often care for these cats, providing them with food, shelter, and medical attention. Despite this, conflicts can arise due to the presence of free-roaming cats, with some individuals advocating for drastic measures such as trapping and killing the cats to reduce their populations. However, it is essential to note that such methods are frequently illegal, inhumane, and ultimately ineffective in most situations. A thorough assessment of the impact of cats on a particular natural area requires a comprehensive cat census, a detailed study of the species being preyed upon, and an investigation into the prevalence of zoonotic or epizootic diseases. Moreover, veterinary experts assert that the public health risks associated with cats are often overstated. This article aims to provide a nuanced perspective on the impact of cats on biodiversity in natural areas, while also discussing their role in transmitting the main zoonotic diseases identified in European countries in recent years, with a particular focus on Spain. Effective cat control programs should focus on non-lethal methods such as trap–neuter–return (TNR) and adoption. TNR has proven to be the most effective and humane method of controlling the free-roaming cat population, but its effectiveness is influenced by several factors, including adoption programs and public education on responsible pet ownership. According to Spanish veterinarians, sustainable and science-based solutions such as TNR programs are the best way to achieve population control of free-roaming cats. The veterinary profession should raise awareness regarding sterilization, vaccination, and identification of cats and the consequences of abandonment. They oppose lethal control and removal of cats from the environment, which are ineffective and unethical methods. To promote animal welfare, veterinary professionals must collaborate with public administrations to implement long-term, sustainable solutions to the problem of cat overpopulation. Greater social awareness regarding the importance of sterilization and identification to prevent abandonment and reduce the number of free-roaming cats is also needed. Despite the challenges presented by homeless cat populations in Spain and the rest of Europe, there are many reasons for optimism. Animal welfare organizations and veterinary professionals are actively collaborating to develop humane and effective solutions to manage community cats, including programs such as TNR and adoption. Furthermore, these initiatives are gaining momentum and support from emerging laws and regulations, such as the recent Spanish animal welfare law. Through these efforts, we can reduce the number of free-roaming cats and improve their quality of life.
... 10 In addition, infection with T. gondii is increasingly being recognized as a problem in non-pregnant, immunocompetent adults, where acute infection may lead to impaired eyesight. 11 Cats are reservoirs for several parasites, some of which are responsible for serious zoonotic diseases. They are the only definitive host of T. gondii and excrete environmentally-resistant oocysts in their feces. ...
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Background: The incidence of toxoplasmosis in humans in Syria indicates an increase in the number of infections with this disease. Cats are the only definitive host of Toxoplasma gondii and excrete environmentally resistant oocysts in their feces. Objectives: Estimate the prevalence of T. gondii-like oocyst shedding in the cat population in Damascus, Syria. Animals: One-hundred domestic cats. Methods: One-hundred fecal samples from cats (68 feral cats and 32 owned cats) were collected in Damascus between October and December 2017 and examined for T. gondii-like oocysts by direct microscopic examination using Sheather's sugar flotation procedure. Results: Examination of the samples showed that 36% (36/100) of the cats were shedding T. gondii-like oocysts. Sporulated or unsporulated oocysts morphologically consistent with T. gondii were detected in 38.2% (26/68) of the samples collected from feral cats and in 31.3% (10/32) of the samples collected from client-owned cats. Conclusion: The clinical importance of Toxoplasmosis in humans lies in the transmission of Toxoplasma to the fetus especially in the first trimester, resulting in severe clinical symptoms in the infant and leading to spontaneous abortion, stillbirth or other serious health problems and severe sequelae (e.g., mental retardation, blindness, hearing, and neurological disorders). Our results showed higher prevalence in Syria than in Lebanon. High amounts of T. gondii-like oocyst shedding were detected in both feral and client-owned cats in Damascus, emphasizing the importance of further research to understand T. gondii infection in people and animals in this region.
... Recent studies have suggested that latent T. gondii infection is not entirely asymptomatic, with evidence of behavioral alterations in both rodents and humans infected with T. gondii such as increased impulsivity, aggression, risky behavior, and suicidal behavior [5,6,7]. Furthermore, many studies have found higher incidence of T. gondii infection in schizophrenia patients as well as anxiety, depression, and other mental health illnesses [8,9]. However, T. gondii infection in the context of drug dependence and the development of substance use disorder (SUD) remain to be elucidated. ...
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Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.
... Toxoplasma gondii (T. gondii) is an obligate intracellular cyst forming apicomplexan parasite, infecting all warmblooded animals including humans, with a cosmopolitan distribution (Rouatbi et al., 2019;Sharif et al., 2009) and is a causative agent of the geographically omnipresent infection known as toxoplasmosis (Rahimi et al., 2015;Sugden et al., 2016). The lactating animals are the significant hosts of T. gondii and thus considered most important transmission route of T. gondii infection. ...
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Toxoplasma gondii is an intracellular zoonotic protozoan parasite usually infects human and animal worldwide. This study aimed to analyze the sero-prevalence of T. gondii in blood of lactating animals and human living in close proximity and also to detect Toxoplasma DNA in unpasteurized milk of the studied animals. A total of 233 blood and milk samples were collected from lactating animals, and 735 blood samples were taken from humans in District Upper Dir, Khyber Pakhtunkhwa, Pakistan. The blood samples were analyzed through ELISA while the milk samples were analyzed by PCR for the presence of T. gondii DNA. A standard questionnaire was introduced to collect the data from the participants. In animals, the reported sero-prevalence was 32.18% for IgM, 17.16% for IgG, and 6.4% for both IgM and IgG. The reported positivity for T. gondii DNA in milk was 14.44%, 34.8%, 20%, and 26% in sheep, goats, cows, and buffaloes, respectively. In the human blood samples, 9.8% were found positive for IgM and 11.2% for IgG while none of the samples was found positive for both IgM and IgG. Overall sero-prevalence reported in females was significantly higher than the male (p<0.05) poor hygiene condition (p < 0.0001) were the significant risk factors associated with T. gondii infections in animals. In conclusion, T. gondii infection is prevalent in lactating animals and humans using their raw milk in the study area. It is suggested that raw milk should be considered as a vehicle for the transmission of T. gondii to humans. Proper pasteurization of milk is very useful in limiting the transmission of infection. Awareness and control programs should be implemented to prevent the infection.
Background: Infectious agents are considered as a possible cause of schizophrenia. The aim of this study was to evaluate the serum levels of cytomegalovirus (CMV), Toxoplasma gondii and Brucella antibodies in schizophrenia patients compared with the control group. Methods: This cross-sectional study was performed on 75 patients with schizophrenia who were clinically diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by two independent psychiatrists. As the controls, 75 sex and age-matched individuals were selected from orthopedic and surgical wards, who were admitted because of trauma. Anti-Toxoplasma gondii IgG antibody was detected by Abbott's company diagnostic kit. To detect anti-Brucella IgG antibodies, the enzyme-linked immunosorbent assay (ELISA) test with Vircell diagnostic kit was used. Quantitative luminescence (CLIA) method using Abbott diagnostic kit was also used to detect anti-cytomegalovirus IgG antibody (CMV IgG avidity). Results: There was not any clinically significant differences in the mean value of Toxoplasma, CMV and Brucella IgG antibodies between schizophrenia and control group. However, considering cut-off point for these tests and further analysis with non-parametric tests showed clinically significant difference between two groups at cut-off point 1.1 for anti-Brucella IgG antibody which indicated more positive samples in schizophrenia group (24 out of 75) than control group (12 out of 75) with a p-value less than 0.05 (0.046). Conclusion: The results of the present study showed no association between toxoplasmosis infection and CMV and schizophrenia. However, there might be a positive correlation between anti-Brucella IgG antibody and schizophrenia.
Background: Cardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. Methods: Using data from 38,803 adults (aged 40-70 years) and followed-up for 5-15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life's Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer's Disease polygenic risk score for all outcomes, among potential confounders. Results: In fully adjusted models, hospital-treated infections were inversely related to GM (β ± SE: -1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (β ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (β ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. Conclusions: Hospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.
Strong evidence exists based on metanalysis of the relationship between toxoplasmosis and many psychiatric diseases: schizophrenia, bipolar disorder, and suicidal behavior. Herein, we estimate the number of cases based on the attributable fraction due to toxoplasmosis on these diseases. The population attributable fraction of mental disease associated with toxoplasmosis was 20,4% for schizophrenia; 27,3% for bipolar disorder; and 0,29% for suicidal behavior (self-harm). The lower and upper estimated number of people with mental disease associated with toxoplasmosis was 4'816.491 and 5'564.407 for schizophrenia; 6'348.946 and 7'510.118,82 for bipolar disorder; and 24.310 and 28.151 for self-harm; for a global total lower estimated number of 11'189.748 and global total upper estimated number of 13'102.678 people with mental disease associated with toxoplasmosis for the year 2019. According to the prediction through the Bayesian model of risk factors for toxoplasmosis associated with mental disease, these varied in importance geographically; thus, in Africa, the most important risk factor was water contamination and in the European region, the cooking conditions of meats. Toxoplasmosis and mental health should be a research priority given the enormous potential impact of reducing this parasite in the general population.
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The Dunedin Multidisciplinary Health and Development Study began more than four decades ago. Unusual at the time, it was founded as a multidisciplinary research enterprise, and was strongly supported by the Dunedin community, both professional and lay, in its early years. Seven research themes have evolved over the past 40 years focusing on mental health and neuro-cognition, cardiovascular risk, respiratory health, oral health, sexual and reproductive health, and psychosocial functioning. A seventh, more applied theme, seeks to maximise the value of the Study findings for New Zealand's indigenous people-Māori (or tangata whenua transl people of the land). The study has published over 1200 papers and reports to date, with almost 2/3 of these being in peer-reviewed journals. Here we provide an overview of the study, its history, leadership structure, scientific approach, operational foci, and some recent examples of work that illustrate the following: (a) the value of multidisciplinary data; (b) how the study is well positioned to address contemporary issues; and (c) how research can simultaneously address multiple audiences-from researchers and theoreticians to policy makers and practitioners. Near-future research plans are described, and we end by reflecting upon the core aspects of the study that portend future useful contributions.
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Neurogenesis is an important process in the regulation of brain function and behaviour, highly active in early development and continuing throughout life. Recent studies have shown that neurogenesis is modulated by inflammatory cytokines in response to an activated immune system. To disentangle the effects of the different cytokines on neurogenesis, here we summarise and discuss in vitro studies on individual cytokines. We show that inflammatory cytokines have both a positive and negative role on proliferation and neuronal differentiation. Hence, this strengthens the notion that inflammation is involved in molecular and cellular mechanisms associated with complex cognitive processes and, therefore, that alterations in brain-immune communication are relevant to the development of neuropsychiatric disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Background: About 30% of people on Earth have latent toxoplasmosis. Infected subjects do not express any clinical symptoms, however, they carry dormant stages of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is mostly considered harmless, however, recent studies showed its specific effects on physiology, behaviour and its associations with various diseases, including psychiatric disorders such as schizophrenia. Individuals who suffer from schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity than controls, which suggests that some traits characteristic of schizophrenic patients, including the sex difference in schizophrenia onset, decrease of grey matter density in specific brain areas and modification of prepulse inhibition of startle reaction could in fact be caused by toxoplasmosis for those patients who are Toxoplasma-seropositive. Methodology/principal findings: We measured the effect of prepulse inhibition/facilitation of the startle reaction on reaction times. The students, 170 women and 66 men, were asked to react as quickly as possible to a startling acoustic signal by pressing a computer mouse button. Some of the startling signals were without the prepulse, some were 20 msec. preceded by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive subjects had longer reaction times than the controls. Acoustic prepulse shorted the reaction times in all subjects. This effect of prepulse on reaction times was stronger in male subjects and increased with the duration of infection, suggesting that it represented a cumulative effect of latent toxoplasmosis, rather than a fading out after effect of past acute toxoplasmosis. Conclusions: Different sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse interaction) suggested, but of course did not prove, that the alternations of prepulse inhibition of startle reaction observed in schizophrenia patients probably joined the list of schizophrenia symptoms that are in fact caused by latent toxoplasmosis.
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Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.
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Background: Neuroinflammation and white matter pathology have each been independently associated with schizophrenia, and experimental studies have revealed mechanisms by which the two can interact in vitro, but whether these abnormalities simultaneously co-occur in people with schizophrenia remains unclear. Method: We searched MEDLINE, EMBASE, PsycINFO and Web of Science from inception through 12 January 2014 for studies reporting human data on the relationship between microglial or astroglial activation, or cytokines and white matter pathology in schizophrenia. Results: Fifteen studies totaling 792 subjects (350 with schizophrenia, 346 controls, 49 with bipolar disorder, 37 with major depressive disorder and 10 with Alzheimer's disease) met all eligibility criteria. Five neuropathological and two neuroimaging studies collectively yielded consistent evidence of an association between schizophrenia and microglial activation, particularly in white rather than gray matter regions. Ultrastructural analysis revealed activated microglia near dystrophic and apoptotic oligodendroglia, demyelinating and dysmyelinating axons and swollen and vacuolated astroglia in subjects with schizophrenia but not controls. Two neuroimaging studies found an association between carrier status for a functional single nucleotide polymorphism in the interleukin-1β gene and abnormal white as well as gray matter volumes in schizophrenia but not controls. A neuropathological study found that orbitofrontal white matter neuronal density was increased in schizophrenia cases exhibiting high transcription levels of pro-inflammatory cytokines relative to those exhibiting low transcription levels and to controls. Schizophrenia was associated with decreased astroglial density specifically in subgenual cingulate white matter and anterior corpus callosum, but not other gray or white matter areas. Astrogliosis was consistently absent. Data on astroglial gene expression, mRNA expression and protein concentration were inconsistent. Conclusion: Neuroinflammation is associated with white matter pathology in people with schizophrenia, and may contribute to structural and functional disconnectivity, even at the first episode of psychosis.
Complex interactions between the immune system and the brain might have important aetiological and therapeutic implications for neuropsychiatric brain disorders. A possible association between schizophrenia and the immune system was postulated over a century ago, and is supported by epidemiological and genetic studies pointing to links with infection and inflammation. Contrary to the traditional view that the brain is an immunologically privileged site shielded behind the blood-brain barrier, studies in the past 20 years have noted complex interactions between the immune system, systemic inflammation, and the brain, which can lead to changes in mood, cognition, and behaviour. In this Review, we describe some of the important areas of research regarding innate and adaptive immune response in schizophrenia and related psychotic disorders that, we think, will be of interest to psychiatric clinicians and researchers. We discuss potential mechanisms and therapeutic implications of these findings, including studies of anti-inflammatory drugs in schizophrenia, describe areas for development, and offer testable hypotheses for future investigations.
Infection with Toxoplasma gondii can cause severe illness when the organism is contracted congenitally or when it is reactivated in immune-suppressed persons. To determine the prevalence of T gondii infection in a representative sample of the US population, the authors tested sera from participants in the Third National Health and Nutrition Examination Survey (1988-1994) for immunoglobulin G antibodies to T. gondii. Of 27,145 persons aged ≥12 years, 17,658 (65%) had sera tested. The overall age-adjusted seroprevalence was 22.5% (95% confidence interval (Cl): 21.1, 23.9); among women aged 15-44 years, seroprevalence was 15.0% (95% Cl: 13.2, 17.0). Age-adjusted seroprevalence was higher in the Northeast (29.2%) than in the South (22.8%), Midwest (20.5%), or West (17.5%) (p < 0.05). In multivariate analysis, risk for T gondii infection increased with age and was higher among persons who were foreign-born, persons with a lower educational level, those who lived in crowded conditions, and those who worked in soil-related occupations, although in subset analyses risk categories varied by race/ethnicity. Nearly one quarter of adults and adolescents in the United States have been infected with T. gondii. Most women of childbearing age in the United States are susceptible to acute infection and should be educated about ways to minimize exposure to T gondii.
The zoonotic pathogen Toxoplasma gondii infects over 1/3 of the human population. The intracellular parasite can persist lifelong in the CNS within neurons modifying their function and structure, thus leading to specific behavioral changes of the host. In recent years, several in vitro studies and murine models have focused on the elucidation of these modifications. Furthermore, investigations of the human population have correlated Toxoplasma seropositivity with changes in neurological functions; however, the complex underlying mechanisms of the subtle behavioral alteration are still not fully understood. The parasites are able to induce direct modifications in the infected cells for example by altering dopamine metabolism, by functionally silencing neurons as well as by hindering apoptosis. Moreover, indirect effects of the peripheral immune system and alterations of the immune status of the CNS, observed during chronic infection, might also contribute to changes in neuronal connectivity and synaptic plasticity. In this review we will provide an overview and highlight recent advances, which describe changes in the neuronal function and morphology upon T. gondii infection.This article is protected by copyright. All rights reserved.