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Journal of Psychiatric Research 148 (2022) 197–203

Contents lists available at ScienceDirect

Journal of Psychiatric Research


journal homepage: www.elsevier.com/locate/jpsychires

Conditional associations between childhood cat ownership and psychotic


experiences in adulthood: A retrospective study
Vincent Paquin a, b, Guillaume Elgbeili b, Julia Munden a, Norbert Schmitz a, c, Ridha Joober a, b,
Antonio Ciampi c, Suzanne King a, b, *
a
Department of Psychiatry, McGill University, Montreal, Canada
b
Douglas University Mental Health Institute, Montreal, Canada
c
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada

A R T I C L E I N F O A B S T R A C T

Keywords: Ownership of cats in childhood has been inconsistently associated with psychosis in adulthood. Parasitic
Psychotic disorders exposure, the putative mechanism of this association, may be more common with rodent-hunting cats, and its
Toxoplasma association with psychosis may depend on other environmental exposures. We examined the conditional asso­
Machine learning
ciations between childhood cat ownership and the frequency of psychotic experiences in adulthood. Adults (n =
Craniocerebral trauma
2206) were recruited in downtown Montreal to complete a survey about childhood cat ownership (non-hunting
or rodent-hunting), winter birth, residential moves in childhood, head trauma history, and tobacco smoking. The
frequency of psychotic experiences (PE) was measured with the 15-item positive subscale of the Community
Assessment of Psychic Experiences. Associations between exposures and PE were examined in linear regressions
adjusted for age and sex. Interactions among variables were explored using a conditional inference tree. Rodent-
hunting cat ownership was associated with higher PE scores in male participants (vs. non-hunting or no cat
ownership: SMD = 0.57; 95% CI: 0.27, 0.86), but not in female participants (SMD = 0.10; 95% CI: − 0.18, 0.38).
In the conditional inference tree, the highest mean PE score was in the class comprised of non-smokers with >1
residential move, head trauma history, and rodent-hunting cat ownership (n = 22; mean standard score = 0.96).
The interaction between rodent-hunting cat ownership and head trauma history was supported by a post-hoc
linear regression model. Our findings suggest childhood cat ownership has conditional associations with psy­
chotic experiences in adulthood.

1. Introduction association between cat ownership and psychotic experiences in humans


(e.g., Bedwell et al., 2020).
Toxoplasma gondii is a candidate causal risk factor for psychosis. This The association between cat ownership and psychotic experiences
protozoan parasite is typically transmitted to humans by domestic cats may be conditional on other factors. Domestic cats generally become
(Dubey, 1998). A seminal case-control study by Torrey and Yolken infected with the parasite by feeding on rodents, and will only be con­
(1995) showed an association between cat ownership during childhood tagious during the days or weeks that follow (Dubey, 1998). Hence,
and the risk for severe mental illness in adulthood. Subsequently, it was specifying whether the cat was known to hunt rodents might provide a
found that seropositivity for T. gondii is associated with a greater number better proxy for probable exposure to T. gondii compared to cat
of psychotic experiences in the general population (Lindgren et al., ownership alone. Another consideration is that the association between
2018), and with a higher risk for schizophrenia (Sutterland et al., 2015). cat ownership and psychotic experiences may be sexually dimorphic:
Additional evidence comes from animal research showing, for example, studies in humans have identified male-specific associations between
that T. gondii infection is associated with activated microglia and syn­ T. gondii infection and behavior or physiology (Flegr et al., 2008, 2011).
aptic loss (Carrillo et al., 2020), two mechanisms that are thought to be Further, as suggested by the multi-hit model of schizophrenia (Davis
involved in the pathogenesis of schizophrenia in humans (Howes and et al., 2016; Howes and McCutcheon, 2017), the presence or absence of
McCutcheon, 2017). Other studies, however, could not demonstrate an other environmental risk factors may influence the association between

* Corresponding author. Mental Health and Society Division, Douglas Research Centre, 6875, boulevard LaSalle, Montreal, QC, H4H 1R3, Canada.
E-mail address: suzanne.king@mcgill.ca (S. King).

https://doi.org/10.1016/j.jpsychires.2022.01.058
Received 2 May 2021; Received in revised form 16 November 2021; Accepted 26 January 2022
Available online 30 January 2022
0022-3956/© 2022 Elsevier Ltd. All rights reserved.
V. Paquin et al. Journal of Psychiatric Research 148 (2022) 197–203

cat ownership and psychosis expression. ownership, and rodent-hunting (i.e., rodent-catching) cat ownership.
Identifying interactions among environmental exposures is an Participants were also asked about their date and place of birth and their
analytical challenge. Environmental risk factors for psychosis are largely level of education. Winter birth was defined as birth in the northern
interconnected (Guloksuz et al., 2018; Paquin et al., 2020). The ability hemisphere between December and March.
of common statistical models, such as linear regressions, to detect in­
teractions will depend on the data analyst’s decisions of which covari­ 2.3. Statistical analysis
ables to include, and which interactions to test for (Guloksuz et al.,
2018; Venkatasubramaniam et al., 2017). Decision tree learning is a Analyses were performed in R version 3.6.1 (R Foundation for Sta­
statistical approach that allows data-driven exploration of interactions tistical Computing). P-values below .05 (two-tailed) were considered
among predictor variables, which are selected by means of an algorithm. significant. Participants with missing data on any of the modeled vari­
This approach generates tree-shaped models of the outcome’s distribu­ ables were removed from the analyses. We conducted descriptive ana­
tion according to the status of selected predictor variables (Hothorn lyses of all participants and compared those included and excluded from
et al., 2006; Venkatasubramaniam et al., 2017). This simple approach to primary analyses due to missingness. For linear regression and decision
machine learning can uncover potential interactions among predictors tree models, we standardized PE scores (i.e., mean = 0, standard devi­
and identify subgroups of participants who share homogeneous expo­ ation [SD] = 1) to facilitate the interpretation of between-individual
sure profiles and symptom levels. differences.
Using retrospective assessments of environmental exposures in a We used linear regression models to examine the associations be­
community sample, we first aimed to examine the association between tween cat ownership and PE standard scores. For exploratory purposes,
rodent-hunting cat ownership in childhood and psychotic experiences in we also reported linear regression models of PE on the other variables:
adulthood. Second, we evaluated whether this association was sexually sex, age, winter birth, residential moves, head trauma history, and
dimorphic. Third, using decision tree learning, we explored potential smoking. Each exposure variable was examined in a separate model
interactions between cat ownership and other risk factors for psychotic adjusted for sex and age. We tested the two-way interaction between sex
experiences. and cat ownership; standardized mean differences (SMD) in PE
depending on cat ownership-by-sex were adjusted for multiple com­
2. Methods parisons using the Tukey method (Lenth, 2020). SMD were interpreted
as small (0.2), medium (0.5) and large (0.8) (Cohen, 1988).
2.1. Participants As a sensitivity analysis for missingness, the aforementioned re­
gressions were fitted on the total sample (n = 2206) imputed with a 5-
This retrospective study was conducted as part of the EnviroGen nearest neighbor algorithm (Kowarik and Templ, 2016). As a sensi­
project, the aim of which was to characterize environmental and genetic tivity analysis for generalizability, the regressions were fitted using
risk factors for psychosis (King et al., 2005). Adults were approached in sample weights derived from Montreal census data (Table S1). Raking
public places in downtown Montreal, Canada to complete a question­ ratio estimation (Kalton and Flores-Cervantes, 2003; Lumley, 2020) was
naire about “unusual psychic experiences”. Participants were required applied to calibrate weights to sex, migration status and educational
to be between 18 and 40 years of age and to live in the greater Montreal attainment.
area. Participants were offered a 1:25 chance of winning $50 if they We used decision tree learning to explore for other interactions
provided contact information. Questionnaires were completed on site among the exposure variables (Venkatasubramaniam et al., 2017). This
and were available in both French and English. Written informed con­ type of machine learning involves recursive partitioning of the data,
sent was given by all participants. This study was approved by the whereby the source dataset is split into multiple subsets based on sta­
Research Ethics Board of the Douglas Research Center. tistical rules. Here, we generated decision trees to predict PE standard
scores based on the status of the exposure variables. We first compared
2.2. Assessments the performance of three decision tree algorithms: conditional inference
trees with Bonferroni corrections, conditional inference trees with the
Psychotic experiences (PE). Participants completed the 42-item Monte Carlo method, and classification and regression trees. In classi­
Community Assessment of Psychic Experiences (CAPE-42) (Brenner fication and regression trees (Breiman, 1984), predictor variables and
et al., 2007; Stefanis et al., 2002). From this scale, the 15-item positive their cutoffs are selected to minimize the relative sum square of errors.
subscale (CAPE-P15) (Capra et al., 2013) was extracted. Its items In contrast, conditional inference trees (Hothorn et al., 2006) select
examine the lifetime occurrence of hallucinatory-like (e.g., hearing predictor variables and their cutoffs according to permutation tests,
voices when alone), delusional-like (e.g., feeling persecuted) and other which are non-parametric and unbiased for predictor selection. We also
unusual experiences (e.g., feeling as though one’s thoughts have been tested linear regressions comprising all the exposure variables, as well as
withdrawn from self). The frequency of each item is self-reported on a generalized linear models using least absolute shrinkage and selection
4-point scale, from “never” (1) to “nearly always” (4). The global score is operator (LASSO) (Friedman et al., 2021) with α = 1. We trained our
the mean weighted frequency of all items. The CAPE-P15 has been models on 75% of the total dataset and cross-validated their perfor­
shown to have good internal consistency, test-retest reliability, construct mances on the remaining 25% of data. We compared the average per­
validity and clinical validity (Bukenaite et al., 2017; Capra et al., 2013; formances of the different models by running 10 iterations of each on
Sun et al., 2020). randomly split datasets.
Risk factors. Participants also completed an ad-hoc questionnaire (see
Supplementary Material) evaluating the presence or absence of the 3. Results
following putative risk factors for psychosis: cat ownership at any time
between birth and age 13, number of residential moves between birth 3.1. Descriptive statistics and correlations
and age 15 (Paksarian et al., 2020), winter birth (Tochigi et al., 2013),
lifetime history of head trauma (Orlovska et al., 2014), and daily to­ Of 3208 participants deemed eligible, 2470 agreed to complete the
bacco smoking (Bhavsar et al., 2018). Participants who had cats in questionnaire (77.0% acceptance), and of those, 2206 were confirmed to
childhood were asked if their cats were known to catch rodents. Cat be eligible. In the total sample (n = 2206), there was no missing data on
hunting behaviors as reported by cat owners were previously shown to PE but 7–26% missing data on the exposure variables. Participants
be associated with T. gondii seroprevalence in the cats (Opsteegh et al., included in primary analyses were those with complete data (n = 1986;
2012). We created a 3-factor cat variable: no cat, non-hunting cat 90.0% of the sample).

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Descriptive analyses are presented in Table 1. The mean PE score was 3.2. Associations between risk factors and psychotic experiences
1.46 (SD = 0.30). Based on the descriptive statistics and predictive
models (see below), we dichotomized age as 0: >21 years, and 1: ≤21 Rodent-hunting cat ownership, but not non-hunting cat ownership,
years. Compared with participants excluded due to missing data, was associated with higher PE scores compared to no cat ownership
included participants had lower PE scores and were more likely to have (Table 2). Winter birth and 1–2 residential moves (relative to none) did
high school education or less and to be born during winter. Compared not display significant associations with the outcome. Age ≤21 years,
with the general population of Montreal, included participants were less having had 3–5 or 6+ residential moves, as well as head trauma history
likely to be immigrants and to have lower educational attainment and smoking, were associated with higher PE scores. Results were
(Table S1). similar in regression models using age as a continuous variable
(Table S2). Sensitivity analyses with sample weights (Table S3) and with
the full, imputed dataset (n = 2206; Table S4) also yielded consistent
results.
There was a significant interaction between rodent-hunting cat
Table 1 ownership and male sex: coefficient = 0.23, standard error (SE) = 0.11, t
Description of included and excluded participants on psychotic experiences, (1979) = 2.23, p = .03. In male participants, rodent-hunting cat
demographic characteristics and environmental exposures.
ownership was associated with higher PE scores (medium effect size)
Included Excluded % missing in excluded compared to non-hunting cat or no cat ownership: SMD = 0.57; 95%
participants
N = 1986 N = 220 confidence interval (CI): 0.27, 0.86. In female participants, this differ­
PE, Mean (SD) 1.45 (0.29) 1.50 0
ence was not significant: SMD = 0.10; 95% CI: − 0.18, 0.38. Alterna­
(0.34) tively, male sex was associated with more PE compared to female sex,
Age group, N (%): 0 but only in participants who owned a rodent-hunting cat: SMD = 0.30;
18–21 years 394 40 95% CI: 0.13, 0.47.
(19.8%) (18.2%)
22–27 years 1008 107
(50.8%) (48.6%) 3.3. Decision tree selection and interaction exploration
28–33 years 386 42
(19.4%) (19.1%)
34–40 years 198 31
Performance analyses and variable importance lists of the decision
(9.97%) (14.1%) trees and regression models can be viewed interactively here: https://vi
Sex, N (%): <1 ncepaquin.shinyapps.io/Cats_and_Rats/. Predictive performances aver­
Female 1030 101 aged over 10 iterations were similar for all three decision tree models
(51.9%) (46.1%)
(conditional inference trees with Bonferroni corrections: mean R2 =
Male 956 118
(48.1%) (53.9%) 3.0%; 95% CI: 2.1, 3.9%; with Monte Carlo method: mean R2 = 3.1%;
Lower educational 0 95% CI: 2.3, 3.8%; classification and regression trees: mean R2 = 3.3%;
attainment, N (%): 95% CI: 2.4, 4.1%). Decision trees underperformed linear regressions
No 1784 207 (mean R2 = 5.5%; 95% CI: 4.5, 6.5%) for prediction. LASSO regressions
(89.8%) (94.1%)
(mean R2 = 5.5%; 95% CI: 4.4, 6.5%) performed similarly to linear
Yes 202 13
(10.2%) (5.91%) regression models comprising all the predictor variables. Of note, in 8 of
Winter birth, N (%): 25.9 the 10 linear regression models comprising all the predictor variables,
No 1601 143 rodent-hunting cat ownership (reference category: no or non-hunting
(80.6%) (87.7%)
cat ownership) was significantly associated with PE scores.
Yes 385 20
(19.4%) (12.3%) We chose the conditional inference tree algorithm with Bonferroni
Cat ownership, N (%): 13.2 corrections for its statistical interpretability and methodological
No cat 995 98 robustness. Across iterations of this algorithm, cutoff for age was set
(50.1%) (51.3%) between 19 and 22 years; for easier interpretability, we refitted the
Non-hunting cat 447 41
models with age dichotomized at 21 years and obtained similar per­
(22.5%) (21.5%)
Rodent-hunting cat 544 52 formances (mean R2 = 3.1%; 95% CI: 2.2, 4.0%).
(27.4%) (27.2%) Among the 10 iterations of conditional inference trees with Bonfer­
Residential moves, N (%): 11.4 roni corrections and dichotomous age, we selected the fourth iteration
0 518 56
(Fig. 1) because it provided the best performance on cross-validation: R2
(26.1%) (28.7%)
1–2 738 68
(37.2%) (34.9%) Table 2
3–5 509 41 Linear regressions of psychotic experience (PE) standard scores on exposures.
(25.6%) (21.0%)
6+ 221 30 Risk factor Coefficient 95% CI Standard error t p
(11.1%) (15.4%) Male sex 0.13 0.04, 0.21 0.04 2.82 .005
Head trauma, N (%): 7.3 Age ≤21 years 0.35 0.24, 0.46 0.06 6.23 <.0001
No 1672 178 Winter birth 0.07 − 0.05, 0.18 0.06 1.16 .25
(84.2%) (87.3%) Cat ownership (reference: no cat)
Yes 314 26 Non-hunting 0.03 − 0.08, 0.14 0.06 0.50 .61
(15.8%) (12.7%) Rodent- 0.17 0.23, 0.28 0.05 3.28 .001
Smoking, N (%): 10.0 hunting
No 1262 113 Residential moves (reference: 0 move)
(63.5%) (57.1%) 1–2 0.07 − 0.04, 0.18 0.06 1.20 .23
Yes 724 85 3–5 0.26 0.14, 0.38 0.06 4.31 <.0001
(36.5%) (42.9%) 6+ 0.42 0.27, 0.58 0.08 5.39 <.0001
Head trauma 0.33 0.21, 0.45 0.06 5.47
Note: Included participants had complete data (i.e., 0% missing data). Lower <.0001
Smoking 0.31 0.22, 0.40 0.05 6.79 <.0001
educational attainment: completed high school or less. PE: psychotic experi­
ences (untransformed score, Community Assessment of Psychic Experiences, 15- Note: Each exposure variable is modeled in a separate linear regression model
item positive subscale, range: 1 to 4). SD: standard deviation. adjusted for age (≤21 years) and sex. CI: confidence interval.

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Journal of Psychiatric Research 148 (2022) 197–203


Fig. 1. Conditional inference tree modeling psychotic experiences (standard scores) according to the number of residential moves before age 15 (“house moves”), history of head trauma, age (younger: ≤ 21 years; older:
> 21 years), smoking, and rodent-hunting cat ownership (versus non-hunting cat or no cat ownership) before age 13.
V. Paquin et al. Journal of Psychiatric Research 148 (2022) 197–203

= 5.8%. Predictors in this tree included rodent-hunting cat ownership, psychotic disorders in adulthood (Paksarian et al., 2020); we showed an
age, residential moves, head trauma, and smoking. The subset of par­ association with PE scores, which appeared to be dose responsive.
ticipants with the highest PE scores was classified as follows: more than Paksarian et al. (2020) similarly identified dose-response patterns of
one residential move, non-smoking, rodent-hunting cat ownership, and associations with residential moves, and showed that these associations
head trauma history (n = 22, mean PE standard score = 0.96). were not explained by genetic factors. As for our finding that male sex is
In 7 of the 10 conditional inference trees with Bonferroni corrections, associated with higher PE scores, other studies do not agree on sex or
there was a similar interplay of non-smoking, head trauma and rodent- gender differences (e.g., McGrath et al., 2015). This inconsistency may
hunting cat ownership associated with higher PE scores. In post-hoc be due to sex or gender differences among specific subtypes of PE
linear regressions adjusted for sex and age, we explored two-way and (Unterrassner et al., 2017), which are captured varyingly by the
three-way interactions between cat ownership and smoking or head different PE measures employed across studies. We could not replicate a
trauma. Only the interaction between rodent-hunting cat ownership and previously observed association between winter birth and PE (Tochigi
head trauma was significant: coefficient = 0.10; SE = 0.04; t(1978) = et al., 2013).
2.61; p = .009. In presence of head trauma history, rodent-hunting cat We found that the association between rodent-hunting cat ownership
ownership was associated with higher PE scores compared to non- and PE was specific to male participants, with a medium effect size
hunting cat or no cat ownership: SMD = 1.06; 95% CI: 0.58, 1.54. compared to non-hunting or no cat ownership. However, this interaction
Also, in presence of head trauma history, non-hunting cat ownership with sex was not identified in the conditional inference tree model,
was reciprocally associated with lower PE scores compared to rodent- indicating sex was not a statistically significant predictor after the
hunting or no cat ownership: SMD = − 0.74; 95% CI: − 1.29, − 0.20. In dataset was partitioned according to other predictors. This suggests that
absence of head trauma, cat ownership had no significant association the other predictors such as head trauma or smoking were more salient
with PE scores. Alternatively, head trauma history was associated with predictors of PE than sex. Evidence for sexually dimorphic effects of
higher PE scores compared to no head trauma history in participants T. gondii exposure is mixed. In a study by Flegr et al. (2008), men but not
who did not own a cat (SMD = 0.25; 95% CI: 0.07, 0.43), and in par­ women who were seropositive for the parasite were shown to have
ticipants who owned rodent-hunting cats (SMD = 0.62; 95% CI: 0.41, higher levels of testosterone compared with controls of the same gender.
0.83), but had no association with PE scores in non-hunting cat owners In another study (Flegr et al., 2011), seropositive men reported greater
(SMD = 0.05; 95% CI: − 0.21, 0.32). attraction for cat urine smell compared with controls, while seropositive
women rated the smell as less pleasant; all participants were blinded to
4. Discussion their infectious status and smell sample identity. A meta-analysis by
Sutterland et al. (2015) did not identify gender as a moderator of the
Cat ownership in childhood was associated with greater psychosis association between T. gondii seropositivity and the risk for schizo­
expression in adulthood, but only in presence of certain factors. Rodent- phrenia, but substantial heterogeneity among included studies may
hunting cat ownership was associated with higher PE scores compared explain the null finding. There is a growing body of evidence that im­
to non-hunting or no cat ownership, which is consistent with our hy­ mune activation early in life has sexually dimorphic effects on
pothesis based on the life cycle of T. gondii as the putative mechanism of psychosis-related phenotypes (Ardalan et al., 2019; Karlsson and Dal­
this association. By using a more granular proxy for parasitic exposure, man, 2020), but these associations may be modified by other genetic or
our study brings a new perspective on previously mixed associations environmental factors.
between cat ownership and psychosis-related phenotypes. Finally, we compared three decision tree learning algorithms which,
Cat ownership does not guarantee exposure to T. gondii, nor is it the in keeping with the literature (Hothorn et al., 2006; Venkatasu­
only source of exposure. For example, ingestion of undercooked meat is bramaniam et al., 2017), had similar performances but underperformed
another major pathway of infection (Dubey, 1998). There are two im­ linear and LASSO regressions. Our final conditional inference tree model
plications of this non-specificity: (1) any association between cat pointed to an interaction between head trauma and rodent-hunting cats,
ownership and psychosis expression does not necessarily demonstrate a which was stable across iterations of the machine learning algorithm
role for parasitic exposure, but (2) if parasitic exposure is indeed the and was supported by an exploratory post-hoc linear regression.
underlying mechanism, then accounting for other risk-enhancing factors Rodent-hunting cat ownership in childhood and head trauma history
may improve the capacity to detect a statistical association. In the pre­ appeared to have synergistic associations with PE in adulthood. One
sent study, we showed that measuring the rodent-hunting behaviors of possible explanation for this is a shared mechanistic pathway impli­
cats provided better risk stratification for PE, possibly because cating glial cells and synaptic loss (Donat et al., 2017; Howes and
rodent-hunting cat ownership is more likely to implicate parasitic McCutcheon, 2017).
exposure than any cat ownership. Other factors related to cat exposure Convenience sampling limits the generalizability of our findings,
may be relevant for identifying proneness to psychosis. For example, although our regression estimates were robust to sample weight ad­
Bedwell et al. (2020) found that cat bites in childhood, but not cat justments. Our study relied on a brief survey targeting a small number of
ownership, were associated with higher PE scores. Considering previous risk factors. The timing and intensity of exposure to cats and head in­
evidence of a high prevalence of T. gondii seropositivity in persons bitten juries were not known. Prior studies suggested that cat exposure in
by their own cats (Westling et al., 2010), the findings from Bedwell et al. childhood, but not during the prenatal period (Torrey and Yolken, 1995)
(2020) may further illustrate the relevance of proxies for parasitic or in adolescence (Bedwell et al., 2020), is associated with psychosis.
exposure that are more precise than cat ownership alone. Exposure to indoor vs. outdoor cats, their hunting other animals, and
Of note, we also modeled the main associations between other ex­ humans’ contacts with other domestic animals (e.g., dogs; Yolken et al.,
posures and PE scores. We replicated evidence that younger age (Sulli­ 2019) may also influence associations with psychosis. As for head
van et al., 2020) and smoking (Bhavsar et al., 2018) are associated with trauma, psychosis may precede and predispose to it (David and Prince,
higher PE scores. Previous studies have supported an association be­ 2005). The association we found might, therefore, represent reverse
tween head trauma and the risk for schizophrenia (David and Prince, causality; however, in a register-based study, it was demonstrated that
2005; Orlovska et al., 2014). Like T. gondii (Carrillo et al., 2020) and accident proneness did not fully explain the prospective association
other risk factors for schizophrenia (Howes and McCutcheon, 2017), between head injury and schizophrenia (Orlovska et al., 2014). Impor­
traumatic brain injury can activate microglial cells and trigger synaptic tant confounders for the associations between exposures and PE were
losses (Donat et al., 2017). Here, we provide evidence of an association not available. For example, cannabis use, parental smoking and genetic
between head trauma and higher PE scores. Residential moves in factors likely confounded the association between smoking and PE to
childhood or adolescence have been associated with a greater risk of some extent. As a result of these unmeasured factors, the decision trees

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