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PubMed2026

Does Toxoplasma gondii infection have a causal impact on human psychopathology? A Mendelian randomization analysis.

Toxoplasma gondii (T. gondii) is a prevalent zoonotic parasite that has been implicated in influencing human psychiatric disorders and risk-taking behaviors. Using genome-wide association study (GWAS) data, we selected 25 and 76 single-nucleotide polymorphisms as instrumental variables for anti-T. gondii IgG seropositivity and anti-T. gondii IgG levels, respectively, and conducted two-sample Mendelian randomization (MR) analyses across 18 GWAS datasets to investigate potential causal effects on addiction, bipolar disorder, obsessive-compulsive disorder, schizophrenia, and risk-taking behavior in European populations. Contrary to previous epidemiological evidence, our MR analyses do not support a significant causal association between T. gondii infection and any of the studied psychiatric disorders or risk-taking behavior. Collectively, these results establish that any true causal effect of genetic liability to T. gondii infection is likely to be small (OR < 1.18 for schizophrenia, < 1.29 for bipolar disorder) and below the effect sizes typically reported in observational seroepidemiological studies, although small or infection-phase-specific effects cannot be excluded.

Humans↗

PubMed2006

Mixed predictability and cross-validation to assess non-linear Granger causality in short cardiovascular variability series.

A method to evaluate the direction and strength of causal interactions in bivariate cardiovascular and cardiorespiratory series is presented. The method is based on quantifying self and mixed predictability of the two series using nearest-neighbour local linear approximation. It returns two causal coupling indexes measuring the relative improvement in predictability along direct and reverse directions, and a directionality index indicating the preferential direction of interaction. The method was implemented through a cross-validation approach that allowed quantification of directionality without constraining the embedding of the series, and fully exploited the available data to maximise the prediction accuracy. Validation on short simulated bivariate time series demonstrated the ability of the method to capture different degrees of unidirectional and bidirectional interaction. Moreover, application to representative examples of heart rate, systolic arterial pressure and respiration series allowed the inference of causal relationships related to known physiological mechanisms and experimental conditions.

Adult↗

PubMed1998

Moral reasoning and the meaning of cancer: causal explanations of oncologists and patients in southern Mexico.

Moral themes were a striking feature of the causal explanations for female cancers discussed by oncologists and patients in an ethnographic study of hospital-based cancer care in southern Mexico. These explanations integrate general biomedical explanations with everyday expectations and experiences, giving meaning to otherwise arbitrary events. Analysis of case examples shows that causal models incorporate local constructs about what constitutes a virtuous life, especially in terms of class-and gender-based values. Although patients and physicians draw on similar concepts of moral order, they apply these constructs in distinct ways. Because physicians' explanations are necessarily framed in terms of object, their causal stories employ generalized presumptions about how categories of persons behave (e.g., women, the lower class). In contrast, patients' explanations are framed in terms of subject; they are based on the specific details of their personal history. The article examines the distinct perspectives of physicians and patients, and provides an illustration of how biomedical culture articulates with the local moral constructs of a particular community.

Adult↗

PubMed2006

Testing causal mechanisms of nonsyndromic craniosynostosis using path analysis of cranial contents in rabbits with uncorrected craniosynostosis.

OBJECTIVE: Various causal mechanisms of familial nonsyndromic craniosynostosis have been presented. One hypothesis suggests that overproduction of bone at the suture is the primary origin of craniosynostosis, which affects brain and cranial growth secondarily through altered intracranial pressure (Primary Suture Fusion Model). Other hypotheses suggest that decreased cranial base growth or abnormal brain growth are the primary cause of craniosynostosis (Cranial Base, Brain Parenchyma Models, respectively). This study was designed to investigate which model best describes neurocranial changes associated with craniosynostosis in a rabbit model through multivariate path analysis. DESIGN: Serial magnetic resonance imaging scans and intracranial pressure measurements were obtained at 10, 25, and 42 days of age from 18 rabbits: six controls, six with delayed-onset synostosis, and six with early-onset synostosis. Five variables were collected from each rabbit: calvarial thickness at the affected suture, cranial base length, brain volume, cerebrospinal fluid volume, and intracranial pressure. This data set was used to test causal pathway relationships generated by the proposed models. Goodness of fit was measured by experimental group for each model. RESULTS: Primary Suture Fusion Model best explained the variables in both delayed-onset and early-onset synostotic rabbits (Goodness of fit = 93%, 97%, respectively). Cranial Base Model (Goodness of fit = 94%) best explained the data in control rabbits. CONCLUSION: Results suggest that the primary site of craniosynostosis in craniosynostotic rabbits is most likely the synostosed suture. Other cranial vault anomalies are most likely secondary compensatory changes. Results of the present study may provide insight regarding the causal pathway of craniosynostosis.

Animals↗

PubMed2023

Pervasive correlations between causal disease effects of proximal SNPs vary with functional annotations and implicate stabilizing selection.

The genetic architecture of human diseases and complex traits has been extensively studied, but little is known about the relationship of causal disease effect sizes between proximal SNPs, which have largely been assumed to be independent. We introduce a new method, LD SNP-pair effect correlation regression (LDSPEC), to estimate the correlation of causal disease effect sizes of derived alleles between proximal SNPs, depending on their allele frequencies, LD, and functional annotations; LDSPEC produced robust estimates in simulations across various genetic architectures. We applied LDSPEC to 70 diseases and complex traits from the UK Biobank (average N=306K), meta-analyzing results across diseases/traits. We detected significantly nonzero effect correlations for proximal SNP pairs (e.g., -0.37±0.09 for low-frequency positive-LD 0-100bp SNP pairs) that decayed with distance (e.g., -0.07±0.01 for low-frequency positive-LD 1-10kb), varied with allele frequency (e.g., -0.15±0.04 for common positive-LD 0-100bp), and varied with LD between SNPs (e.g., +0.12±0.05 for common negative-LD 0-100bp) (because we consider derived alleles, positive-LD and negative-LD SNP pairs may yield very different results). We further determined that SNP pairs with shared functions had stronger effect correlations that spanned longer genomic distances, e.g., -0.37±0.08 for low-frequency positive-LD same-gene promoter SNP pairs (average genomic distance of 47kb (due to alternative splicing)) and -0.32±0.04 for low-frequency positive-LD H3K27ac 0-1kb SNP pairs. Consequently, SNP-heritability estimates were substantially smaller than estimates of the sum of causal effect size variances across all SNPs (ratio of 0.87±0.02 across diseases/traits), particularly for certain functional annotations (e.g., 0.78±0.01 for common Super enhancer SNPs)-even though these quantities are widely assumed to be equal. We recapitulated our findings via forward simulations with an evolutionary model involving stabilizing selection, implicating the action of linkage masking, whereby haplotypes containing linked SNPs with opposite effects on disease have reduced effects on fitness and escape negative selection.

Journal Article↗

PubMed2026

Causal Relationships Between Modifiable Risk Factors and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder, yet the causal roles of modifiable risk factors remain unclear. This study aims to investigate the causal relationships between 28 modifiable risk factors (including obesity traits, mental health disorders, sleep traits, metabolic comorbidities, and serum parameters) and GERD using two-sample Mendelian randomization (MR). Gastroesophageal reflux disease (GERD). Our findings aim to inform targeted prevention and treatment strategies for GERD. METHODS: This study obtained data from extensive genome-wide association studies (GWAS). Pooled data associated with gastroesophageal reflux associations were obtained from the 23andMe Research team's research, which included a total of 129,080 cases of gastroesophageal reflux and 473,524 controls of European ancestry. We conducted a univariable Mendelian randomization (MR) analysis to ascertain whether genetic evidence of exposure demonstrated a statistically significant association with the risk of GERD. Subsequently, a multivariable MR analysis was carried out to estimate the independent effects of the exposures on GERD. RESULTS: Univariable MR analysis utilizing extensive GWAS data suggested that genetic factors such as BMI, Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), Attention Deficit and Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Schizophrenia, Negative emotions (including nervousness, anxiety, tension, or depression), Insomnia, Sleep apnea syndrome, Sleep duration, and Snoring, as well as Total cholesterol levels and Apolipoprotein B levels, are associated with the development of GERD. Multivariate Mendelian randomization of BMI and Negative emotion as correction factors showed that Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), ADHD, Insomnia, Sleep apnea syndrome, and Snoring were associated with an increased risk of GERD (p< 0.05). Conversely, longer sleep duration was associated with a reduced risk of GERD (p< 0.05). DISCUSSION: This MR study reveals novel causal mechanisms in GERD pathogenesis: (1) Peripheral adiposity (arm/leg fat mass) exerts independent effects beyond central obesity, indicating site-specific fat distribution significance; (2) ADHD emerges as a distinct psychiatric risk factor independent of mental disorders; (3) Sleep apnea operates through BMI-independent pathways. Collectively, these findings redefine GERD pathophysiology, highlighting fat depot specificity and brain-gut interactions as critical mechanistic drivers. CONCLUSION: Overall, our findings suggest that multiple risk factors are associated with the risk of GERD. These results provide a theoretical basis for controlling body weight and plasticity, improving sleep habits, and preventing and timely seeking medical attention to reduce the occurrence of psychiatric disorders, which will be important strategies to prevent and alleviate GERD.

Humans↗

PubMed1990

Causal attributions of physical education majors and mentally retarded adults.

This exploratory study examined the causal attributions and expectancies of 51 physical education majors and 25 mentally retarded adults. The majors completed a written questionnaire concerning their causal attributions and expectancies for motor performance of the adults. The adults responded through an interview procedure regarding causal attributions and expectancies for their own motor performance. Analysis did not support the hypothesis that people make stable attributions about the performance of mentally retarded populations and subsequently maintain low expectancies. Previous experiences of failure did not diminish the expectancies of the adults for their own future success.

Achievement↗

PubMed1991

Therapists' causal attributions of clients' problems and selection of intervention strategies.

Therapists' choices of intervention strategies are influenced by many factors, including judgments about the bases of clients' problems. To assess the relationships between such causal attributions and the selection of intervention strategies, 196 counselors, psychologists, and social workers responded to the written transcript of a client's interview by answering two questionnaires, a 1982 scale (Causal Dimension Scale by Russell) which measured causal attribution of the client's problem, and another which measured preference for emotional, rational, and active intervention strategies in dealing with the client, based on the 1979 E-R-A taxonomy of Frey and Raming. A significant relationship was found between the two sets of variables, with internal attributions linked to rational intervention strategies and stable attributions linked to active strategies. The results support Halleck's 1978 hypothesis that theories of psychotherapy tie interventions to etiological considerations.

Adult↗

PubMedDate not supplied

Child overdose: the value of the French pharmacovigilance causality assessment method.

BACKGROUND: In France, the regional pharmacovigilance centres manage drug overdose as adverse drug reactions (ADRs) using the French ADR causality assessment method, and some poison control centres (e.g. in Paris) do likewise for the most serious cases. AIM: The aim of the study was to analyse and compare the chronological and semiological scores calculated with this method, in cases of drug overdose and ADRs in children recorded in the French pharmacovigilance ADR database. RESULTS: In total, 7963 cases were analysed. The distribution of semiological criteria in drug overdose and ADR cases differed significantly (G-test), with a similar result for chronological criteria (but to a lesser degree). CONCLUSION: The distinction of two types of criteria in the French ADR causality assessment method appears useful for analysing cases of drug overdose in children. This finding triggers a renewed interest in the use of this method of causality assessment of drug overdose in children, and possibly in adults.

Age Factors↗

PubMed2005

What affects self-esteem of persons with psychiatric disabilities: the role of causal attributions of mental illnesses.

This study addresses the factors which affect the self-esteem of persons with psychiatric disabilities, with a specific focus on the role of causal attributions of mental illnesses. It is based on data collected from 461 persons with psychiatric disabilities (consumers) served through psychiatric rehabilitation agencies. The results of regression analyses revealed that household income, diagnosis, psychiatric symptoms, service satisfaction, perceived stigma, and perceptions of social roles were all related to self-esteem. Consumers' causal attributions did not have direct effects on self-esteem, but the effects of causal attributions on self-esteem were moderated by psychiatric symptoms and by perceptions of social roles, suggesting that self-esteem enhancement strategies should be tailored to consumers' psychiatric and cognitive characteristics.

Adult↗

PubMed2005

Accessing causal relations in semantic memory.

Most studies investigating semantic memory have focused on taxonomic or associative relations. Little is known about how other relations, such as causal relations, are represented and accessed. In three experiments, we presented participants with pairs of words one after another, describing events that referred to either a cause (e.g., spark) or an effect (e.g., fire). We manipulated the temporal order of word presentation and the question participants had to respond to. The results revealed that questions referring to the existence of a causal relation are answered faster when the first word refers to a cause and the second word refers to its effect than vice versa. However, no such asymmetry was observed with questions referring to the associative relation. People appear to distinguish the roles of cause and effect when queried specifically about a causal relation, but not when the same information is evaluated for the presence of an associative relation.

Humans↗

PubMed2002

Momentary and integrative response strategies in causal judgment.

Associative models of causal learning predict recency effects. Judgments at the end of a trial series should be strongly biased by recently presented information. Prior research, however, presents a contrasting picture of human performance. López, Shanks, Almaraz, and Fernández (1998) observed recency, whereas Dennis and Ahn (2001) found the opposite, primacy. Here we replicate both of these effects and provide an explanation for this paradox. Four experiments show that the effect of trial order on judgments is a function of judgment frequency, where incremental judgments lead to recency while single final judgments abolish recency and lead instead to integration of information across trials (i.e., primacy). These results challenge almost all existing accounts of causal judgment. We propose a modified associative account in which participants can base their causal judgments either on current associative strength (momentary strategy) or on the cumulative change in associative strength since the previous judgment (integrative strategy).

Adolescent↗

PubMed2005

Contrasting predictive and causal values of predictors and of causes.

Three experiments examined human processing of stimuli as predictors and causes. In Experiments 1A and 1B, two serial events that both preceded a third were assessed as predictors and as causes of the third event. Instructions successfully provided scenarios in which one of the serial (target) stimuli was viewed as a strong predictor but as a weak cause of the third event. In Experiment 2, participants' preexperimental knowledge was drawn upon in such a way that two simultaneous antecedent events were processed as predictors or causes, which strongly influenced the occurrence of overshadowing between the antecedent events. Although a tendency toward overshadowing was found between predictors, reliable overshadowing was observed only between causes, and then only when the test question was causal. Together with other evidence in the human learning literature, the present results suggest that predictive and causal learning obey similar laws, but there is a greater susceptibility to cue competition in causal than predictive attribution.

Adult↗

PubMed2003

Forward and backward blocking of causal judgment is enhanced by additivity of effect magnitude.

When two causes for a given effect are simultaneously presented, it is natural to expect an effect of greater magnitude. However many laboratory tasks preclude such an additivity rule by imposing a ceiling on effect magnitude-for example, by using a binary outcome. Under these conditions, a compound of two causal cues cannot be distinguished from a compound of one causal cue and one noncausal cue. Two experiments tested the effect of additivity on cue competition. Significant but weak forward blocking and no backward blocking were observed in a conventional "allergy" causal judgment task. Explicit pretraining of magnitude additivity produced strong and significant forward and backward blocking. Additivity pretraining was found to be unnecessary for another cue competition effect, release from overshadowing, which does not logically depend on additivity. The results confirm that blocking is constrained when effect magnitude is constrained and provide support for an inferential account of cue competition.

Adult↗

PubMed1996

Causal order does not affect cue selection in human associative learning.

Waldmann and Holyoak (1992) presented evidence in support of the claim that cue selection does not emerge in "diagnostic" human learning tasks in which the cues are interpretable as effects and the outcomes as the causes of those effects. Waldmann and Holyoak argued that this evidence presents a major difficulty for associationist theories of learning and instead supports a "causal model" theory. We identify a number of flaws in Waldmann and Holyoak's experimental procedures and report three new experiments designed to test their claim. In Experiment 1, cue selection was observed regardless of causal order and regardless of whether the cues were abstractly or concretely specified. In Experiments 2 and 3, cue selection was again observed when subjects predicted causes from effects. We conclude that our results are consistent with simple associationist theories of learning but contradict Waldmann and Holyoak's causal model theory.

Adult↗

PubMed1993

Causal prophylactic and radical curative activity of WR182393 (a guanylhydrazone) against Plasmodium cynomolgi in Macaca mulatta.

Primaquine is the only currently available drug effective against persistent tissue stages of relapsing malaria in humans. Causal prophylactic and radical curative properties of WR182393 (a guanylhydrazone) were investigated as part of an effort to evaluate alternatives to primaquine in the rhesus monkey (Macaca mulatta)/Plasmodium cynomolgi test model. The drug was suspended in dimethylsulfoxide for intramuscular (im) injection. A pilot study indicated causal prophylactic activity in a regimen of 40 mg base/kg/day im for three days beginning the day before intravenous challenge with 1 x 10(6) P. cynomolgi sporozoites. Regimens of 31, 10, 3.1, and 0 mg base/kg/day im for three days were then tested in groups of two monkeys given a similar challenge. The two animals given 31 mg base/kg/day remained parasite-free. Average time to parasitemia for the lower dosage groups was 38, 18, and 8 days respectively. Groups of two monkeys with sporozoite-induced P. cynomolgi infections were also treated for seven days with 31, 10, 3.1, and 0 mg base/kg/day im in combination with 10 mg base/kg/day of chloroquine orally. Both monkeys given 31 mg base/kg/day did not relapse. The average time to relapse following treatment was 48, 29, and 8 days, respectively, for the lower dosage groups. Compound WR182393 is the first non-8-aminoquinoline class of drug to exhibit both causal prophylactic and radical curative properties against a relapsing primate, vivax-like malaria.

Animals↗

PubMed2005

Effect of the lactoperoxidase system against three major causal agents of disease in mangoes.

The antibacterial activity of the lactoperoxidase system (LPS) on the growth of Xanthomonas campestris, the causal agent of bacterial black spot in mangoes, Botryodiplodia theobromae, the causal agent of stem-end rot disease in mangoes, and Colletotrichum gloeosporioides, the causal agent of anthracnose disease in mangoes, was determined during culture at 30 degrees C and at several pH values (4.5, 5.5, and 6.5). When the results of using the LPS were compared with those from control cultures without the LPS reagents, the growth of the three microorganisms was totally inhibited in all of the conditions tested. Viability tests enumerating cultivable cells of X. campestris showed that the LPS had a bactericidal effect, whatever the pH value. This effect is faster at pH 5.5, corroborating the results reported in the literature (optimal pH for the LPS efficiency). Further, we proved that hydrogen peroxide alone had little inhibition effect on the growth of the microorganisms studied. This compound is essentially used to convert thiocyanate into hypothiocyanate during the lactoperoxidase reaction. The potential of the LPS for the postharvest treatment of the fruits for controlling microbial diseases was thus demonstrated. Nevertheless, further studies are needed on fresh fruits before envisaging any application.

Anti-Bacterial Agents↗

PubMed2004

[Examining the causal model of depression: the relation between depressogenic schemata and depression].

This study examines the causal relation between depressogenic schemata and depression. Three structural equation models were tested two times among 149 students during five months: (1) one-way causal relation from depressogenic schemata to depression, (2) one-way causal relation from depression to depressogenic schemata, (3) reciprocal relation between depressogenic schemata and depression. Results showed the third model is the most adequate among three models. It is possible that depressogenic schemata influences depression and depression also has some effects on depressogenic schemata. As a result of reviewing previous studies, it is thought that there is a continuity is between clinical and non-clinical groups. Therefore, the findings of this study is useful in understanding the clinical image of depression.

Adolescent↗