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PubMed1993

Generating and testing a causal explanation of the gender difference in age at first onset of schizophrenia.

Motivated by the lack of knowledge of the pathophysiological processes underlying the manifestation of symptoms in schizophrenia, we have worked out a systematic search strategy. Since epidemiological distribution patterns consistently deviating from expected values provide valuable indications of causal relationships, we chose the higher age of females at first admission for schizophrenia, first reported by Kraepelin and since then confirmed in over 50 studies, as the basis for our study. This unexplained epidemiological finding was replicated on Danish and Mannheim case-register data by systematically controlling for selection and diagnostic artefacts and by testing alternative explanations at the individual stage of the study. To check whether the difference in age at first admission was determined by a difference in age at onset, a representative sample of 267 first-admitted patients with non-affective functional psychosis was examined by using an interview for the retrospective assessment of the onset of schizophrenia (IRAOS) designed for this purpose. Any of the definitions of first-ever onset applied--first sign of mental disorder, first psychotic symptom, first acute episode--led to a significant age difference of 3.2 to 4.1 years between the sexes. The distribution of onsets across the life cycle showed a later increase and a second, lower peak between the ages of 45 and 54 years among females compared with males. The lifetime risk for schizophrenia was equal for males and females. After testing the plausibility of psychosocial versus biological explanations we hypothesized that due to the effect of oestrogens the vulnerability threshold for schizophrenia is elevated in females until the menopause. Animal experiments and post mortem analyses showed that chronic oestrogen applications significantly shortened dopamine-induced behaviour and reduced D2 receptor sensitivity in the brain. The applicability of this pathophysiological mechanism to human schizophrenia was tested on acutely schizophrenic females with normal menstrual cycles. A significant negative correlation was found between measures of symptomatology and plasma oestrogen levels. The manifestation of symptoms in schizophrenia appears to be influenced by a sufficiently sensitive D2 receptor system in the brain, blocked by neuroleptics and modulated by oestrogens.

Age Factors↗

PubMed1996

Causal attributions about common somatic sensations among frequent general practice attenders.

The causal attributions that people make about bodily symptoms or sensations are likely to influence their decisions whether or not to consult a doctor. Previous research has supported the model that people tend initially to look for external or environmental explanations for bodily sensations (normalizing attributions) and only if this process fails do they search for attributions internal to themselves (somatic or psychological attributions). This study tested two hypotheses about frequent general practice attenders: (1) compared with others, they are more likely to make somatic attributions and less likely to make normalizing ones; and (2) given a bodily symptom together with a somatic explanation, frequent attenders will have greater difficulty than others in finding reasons why the given (pathological) explanation is untrue. The frequent attenders' group had themselves initiated an average of 12 general practice visits in the 12 months before assessment, while a control group of infrequent attenders had not made appointments to see their general practitioner for an average of 24 months. The results provide partial support for the hypotheses. Frequent attenders generated significantly fewer normalizing explanations for a series of common bodily sensations than the comparison group, although the two groups did not differ in their somatic attributions. Given a common bodily sensation and an accompanying pathological explanation, the frequent attenders were less able than the control group to generate reasons why the given explanation might be untrue. Some associations were found between these measures and anxiety.

Adult↗

PubMed2001

Causal attributions for somatic sensations in patients with chronic fatigue syndrome and their partners.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) often make somatic attributions for their illness which has been associated with poor outcome. A tendency to make somatic attributions in general may be a vulnerability factor for the development of CFS. METHODS: This cross-sectional study based on self-report questionnaire data aimed to investigate the type of attributions for symptoms made by patients with CFS and to compare this to attributions made by their partners. It was hypothesized that patients with CFS would make more somatic attributions for their own symptoms than control subjects and that partners of patients with CFS would make more somatic attributions for their ill relative's symptoms but would be similar to controls regarding their own symptoms. Fifty patients with CFS were compared to 50 controls from a fracture clinic in the same hospital and 46 relatives living with the patients with CFS. A modified Symptom Interpretation Questionnaire was used to assess causal attributions. RESULTS: CFS patients were more likely to make somatic attributions for their symptoms. The relatives of patients with CFS made significantly more somatic attributions for symptoms in their ill relative. However, they were like the fracture clinic controls in terms of making predominantly normalizing attributions for their own symptoms. CONCLUSIONS: The data support modification of existing cognitive behavioural treatments for CFS to investigate whether addressing partners' attributions for patients' symptoms improves recovery in the patient. Furthermore, a tendency to make somatic attributions for symptoms may be a vulnerability factor for the development of CFS.

Adolescent↗

PubMed2005

Exposure-pathway models explain causality in whole sediment toxicity tests.

Measurements of lethal effect concentrations (LC50) and bioaccumulation following water-only and whole-sediment exposures of the amphipod, Melita plumulosa, and the bivalve, Tellina deltoidalis, to copper, were combined with bioenergetic-based kinetic models of exposure pathways to explain causality in whole-sediment toxicity tests. For both organisms, lethal body concentrations (LBCs) were greater for water-only exposures than for sediment exposures and indicated that the rate of copper accumulation and/or the mode of toxicity of copper assimilated were different for dissolved and particulate phases. The net assimilation of copper, expressed as a lethal exposure concentration (LEC) that was independent of the postexposure copper efflux, was shown to better explain the observed toxicity. The LEC of copper was the same for both water-only and whole-sediment toxicity tests. It is predicted that, for each species, a large range of effect concentrations may be measured for sediments having the same total copper concentration. These are conditional effect concentrations, as their value will be determined by total copper concentrations, partitioning (Kd) relationships (sediment properties), organism physiology (uptake rates from waters, assimilation efficiencies from solids), and organism feeding behavior (feeding selectivity). The importance of these factors to the development of sediment quality guidelines for metals based on species sensitivity distributions is discussed.

Amphipoda↗

PubMed2005

Inhibiting effects of resveratrol and its glucoside piceid against Venturia inaequalis, the causal agent of apple scab.

Resveratrol is a phytoalexin produced in different unrelated plant species such as grapevine and peanut. The effect of resveratrol and its glucoside trans-resveratrol-3-O-beta-D-glycopyranosid (piceid) against Venturia inaequalis, the causal agent of apple scab, was evaluated using a newly established test based on enzymatically isolated cuticular membranes (CMs) from apple (Malus domestica Borkh.) leaves. The test substances resveratrol and piceid were either sorbed to CMs before inoculation with spores or were applied simultaneously with the Venturia inaequalis spores to the CMs, and their effect on germination, appressoria formation, and penetration was examined. Resveratrol had no influence on spore germination but a significant inhibiting effect on penetration when applied simultaneously as well as before. A percentage inhibition of 89.7 +/- 11.5 and 61.8 +/- 35.1 was observed for simultaneous and preapplication, respectively. The resveratrol glucoside piceid had a significant inhibitory effect on germination and completely inhibited penetration of the fungus at concentrations between 200 and 400 microg mL(-1) when applied simultaneously with the spores to the CMs. On piceid-enriched CM (preapplication), spores germinated but penetration was inhibited nearly completely (96.1 +/- 5.1%). Thus, in vitro experiments showed that resveratrol and its glucoside in fact could contribute to improving the pathogen resistance of apple leaves.

Ascomycota↗

PubMed1999

Why do cohabiting couples marry? An example of a causal event history approach to interdependent systems.

The purpose of this paper is to demonstrate a causal approach to interdependent systems based on two empirical investigations. These examples demonstrate 1) the study of two highly interdependent processes: entry into first marriage as the dependent process and the process of first birth/first pregnancy as the explaining one; 2) an interdependence occurring mainly in a very specific phase of individuals' lives (i.e., during the period of first family formation); 3) the involvement of time lags between cause and its effect (e.g., time until detection of conception); and 4) the highly dynamic character of an unfolding effect over time (i.e., the effect of first pregnancy/first birth on first marriage strongly depends on the progress of pregnancy and the time since the birth has taken place).

Birth Intervals↗

PubMed1998

Mammographic breast density and risk of breast cancer: masking bias or causality?

Masking bias is hypothesized to explain associations between breast density and breast cancer risk. Tumours in dense breasts may be concealed at the initial examination, but manifest themselves in later years, suggesting an increase in breast cancer incidence. We studied the association between breast density and breast cancer risk in 0, 1-2, 3-4 and 5-6 year periods between initial examination and diagnosis. We studied 359 cases and 922 referents, identified in a breast cancer screening programme in Nijmegen, The Netherlands. Breast density was assessed at the initial examination and classified as 'dense' (if > 25% of the breast was composed of density) or 'lucent' (< or = 25% density). In women examined with mid-1970s film screen mammography, we found that at time 0 the odds ratio (OR) for women with dense breasts compared to those with lucent breasts was 1.4 (95% confidence interval (CI): 0.7-6.2). After a 3-4 year period the risk was increased to 3.3 (95% CI: 1.5-7.1). Then, the risk decreased again (OR: 1.2, 95% CI: 0.6-2.7). This rise and decline in risk are in accordance with the masking hypothesis. The observation, however, that the risk at time 0 does not appear to be lower for women with dense breasts than for those with lucent breasts, seems to be inconsistent with the masking hypothesis and may be indicative of causality. The same analysis were performed in women whose initial screening examination was done with current high-quality mammography. Due to the small size of this study group no firm conclusions could be drawn, but it seems as if masking bias could still play a role with high-quality mammography.

Adult↗

PubMed2000

Predictive inference, causal reasoning, and model assessment in nonparametric Bayesian analysis: a case study.

This paper continues our earlier analysis of a data set on acute ear infections in small children, presented in Andreev and Arjas (1998). The main goal here is to provide a method, based on the use of predictive distributions, for assessing the possible causal influence which the type of day care will have on the incidence of ear infections. A closely related technique is used for the assessment of the nonparametric Bayesian intensity model applied in the paper. Two graphical methods, supported by formal tests, are suggested for this purpose.

Algorithms↗

PubMed1998

The notion of "killing". Causality, intention, and motivation in active and passive euthanasia.

As a new approach to the still unsettled problem of a morally significant difference between active and passive euthanasia, the meanings of the notion of killing are distinguished on the levels of causality, intention, and motivation. This distinction allows a thorough analysis and refutation of arguments for the equality of killing and letting die which are often put forward in the euthanasia debate. Moreover, an investigation into the structure of the physician's action on those three levels yields substantial differences between the two ways of acting. As can be demonstrated, only a teleological notion of the organism is able to grasp the characteristic feature of active euthanasia. On this basis it is argued that an action against the organism as a whole must, on the interpersonal level, be at once directed against the patient as a person himself.

Attitude↗

PubMed2001

Possible causal relationships between cerebellar patterns of foliation and hindlimb coordination in laboratory mice: a quantitative trait locus analysis.

The cerebellum is involved in a large set of integrative functions including memory, affect, and motricity. The cerebellar patterns of foliation and their causal relationships with motricity were investigated via a wide genome scan approach and quantitative trait locus (QTL) strategy. QTLs were mapped in an F2 population derived from NZB/B1NJ and C57BL/6By inbred strains of mice for cerebellar fissures in the four vermal lobules (intraculminate, uvula, declival, and intracentral) and for hindpaw slips in a bar crossing test. No linkage was detected for uvula and intracentral fissures. We found five QTLs linked to declival fissure: Cpfd-1q and Cpfd-2q (chromosome 1), Cpfd-3q (chromosome 5), Cpfd-4q (chromosome 9), and Cpfd-5q (chromosome 13). Two QTLs were also mapped for intraculminate fissure Cpfi-1q (chromosome 4) and Cpfi-2q (chromosome 1). Most of the confidence intervals of these QTLs included genes that were previously identified for their implication in the physiological mechanisms underlying cerebellar patterns of foliation. Only one significant QTL was found for the measure of hindpaw coordination (Tne-1q). It was linked with Cpfd-1q and Cpfd-2q on the telomeric part of chromosome 1.

Animals↗

PubMed2001

The hopelessness theory of depression: a test of the diathesis-stress and causal mediation components in third and seventh grade children.

The goal of the current study was to test the diathesis-stress and causal mediation components of the hopelessness theory of depression in third- and seventh-grade children. The procedure involved an initial assessment of depressive symptoms, hopelessness, and the 3 cognitive styles posited as vulnerability factors by hopelessness theory. The procedure also involved a series of 6 weekly follow-up assessments in which depressive symptoms, hopelessness, and the occurrence of negative events were assessed. A depressogenic attributional style interacted with negative events to predict increases in depressive symptoms in seventh-grade children but not in third-grade children. A depressogenic inferential style about consequences interacted with negative events to predict increases in depressive symptoms in both third- and seventh-grade children. Last, a depressogenic inferential style about the self interacted with negative events to predict increases in depressive symptoms in third- and seventh-grade girls but not boys. None of these interactions were mediated by hopelessness.

Adaptation, Psychological↗

PubMed2001

Identification and survival of the causal organism of leaf smut disease of cowpea in Nigeria.

Protomycopsis phaseoli (Ramak and Subram) is the causal agent of the cowpea leaf smut disease in Nigeria and not Entyloma vignae as claimed by some authors. This pathogen formed dark ash-grey to sooty-black lesions of 3-10 mm in diameter, while young lesions had yellow haloes. P. phaseoli produced dark reddish-brown chlamydospores that are globose to oval measured 23.8 microm, thick-walled and rugose. The chlamydospores germinated and produced globose vesicles. The pathogen grew on potato dextrose agar only when the leaf tissue was dipped in acidified water (1% H2SO4). The organism was slowly growing at 24-28 degrees C with snow white colour. Chlamydospores of P. phaseoli in infected cowpea leaves survived longer when buried in the soil for five months than when they were left on the soil surface for the same period at temperatures (26-27 degrees C) and humidity (70-82%) prevailing in Ibadan. Destruction of leaf debris before crop emergence, long period of rotation and no tillage cropping are suggested to prevent the onset and spread of leaf smut disease of cowpea.

Ascomycota↗

PubMed2002

No causal association between inflammation and Chlamydia pneumoniae in patients with chronic ischemic arterial disease.

The C-reactive protein, Chlamydia-specific IgG antibody, and fibrinogen were assayed in the serum of 159 patients with arterial disease (the arterial group) and 203 patients with heart valve prostheses (the valvular group) and no demonstrable coronary disease. In the arterial group, the Chlamydia pneumoniae antibody was > or = 1:32 for 67.3% (107/159) of the patients, the C-reactive protein was elevated in 41.5% (66/159), and the fibrinogen was elevated in 27.7% (44/159). In the valvular group, the C. pneumoniae antibody was > or = 1:32 for 59.1% (120/203) of the patients; the C-reactive protein was elevated in 34.0% (69/203), and the fibrinogen was elevated in 17.2% (35/203). Of 107 patients in the arterial group with C. pneumoniae titers > or = 1:32, only 26 (24.3%) had elevated fibrinogen (426 +/- 29 mg/dL) and 44 (41.1%) had elevated C-reactive protein (1.06 +/- 0.52 mg/dL). Similarly, of the 120 patients in the valvular group with C. pneumoniae titers > or = 1:32, 17 (14.2%) had elevated fibrinogen (409 +/- 29 mg/dL) and 34 had elevated C-reactive protein (0.99 +/- 1.1 mg/dL). Correlated poorly was C. pneumoniae with C-reactive protein and fibrinogen levels. Only the fibrinogen level could be discriminated between the arterial and the valvular group. These results suggest that no causal association exists between inflammation and C. pneumoniae. A highly significant correlation between C-reactive protein and fibrinogen levels was found.

Adolescent↗

PubMed2002

Induced chitinase activity in resistant wheat leaves inoculated with an incompatible race of Puccinia striiformis f. sp. tritici, the causal agent of yellow rust disease.

Chitinase specific activity was measured spectrophotometrically in wheat leaf tissues during the compatible and incompatible interactions with Puccinia striiformis f. sp. tritici, the causal agent of yellow rust disease. The wheat cultivar, Federation* 4/Kavkaz, was inoculated with virulent (134E134A+) or avirulent (4EOA+) races of P. striiformis f. sp. tritici in the first leaf stage. The results showed that chitinase activity pattern was similar in both compatible and incompatible interactions up to 72 hrs after inoculation. However, the specific activity increased rapidly in the incompatible reaction thereafter. In susceptible reaction, chitinase activity gradually declined after 72 hrs post-inoculation reaching a level similar to that in the control plants two weeks after inoculation. Chitinase specific activity in resistance response was at least three times greater than that in the susceptible reaction two weeks following the inoculation. Electrophoresis of native polyacrylamide gel impregnated with 0.1% (w/v) glycol chitin as the substrate revealed the presence of eight chitinase isoforms with relative electrophoretic mobility (Rm) values ranging from 0.11 to 0.64 in the resolving gel.

Basidiomycota↗

PubMed2002

Evidence for the causal role of endogenous interferon-alpha/beta in the regulation of angiogenesis, tumorigenicity, and metastasis of cutaneous neoplasms.

Primary tumor growth and metastasis depend on angiogenesis, which is determined by the balance between proangiogenic and antiangiogenic molecules. Interferon (IFN)-alpha and -beta inhibit angiogenesis through downregulation of interleukin-8, matrix metalloproteinase-9, and basic fibroblast growth factor. To provide evidence for the causal role of IFN-alpha/beta in the induction of neoplasms, their angiogenesis, and hence, progressive growth, we carried out experiments using 129S6 IFN-alpha/beta receptor -/- mice back-crossed to BALB/c nude mice. Subcutaneous angiogenesis was determined following implantation of gelfoam sponges containing 0.4% agarose and several proangiogenic molecules. Tumorigenicity and production of lung metastasis were determined subsequent to subcutaneous and intravenous injections, respectively, of highly metastatic A375SM human melanoma cells. Carcinogenesis was induced by chronic exposure of mice to UVB radiation (5 kJ/m2, 3 times/week). Angiogenesis, tumorigenicity, and production of metastasis, as well as development of autochthonous skin tumors, were all accelerated in IFN-alpha/beta receptor -/- mice as compared to control mice. Collectively, the data show that inability to respond to endogenous IFN-alpha/beta (through a mutation in the IFN-alpha/beta receptor) leads to increased susceptibility to carcinogenesis, enhanced angiogenesis, tumorigenicity, and metastasis.

Angiogenesis Inhibitors↗

PubMed2003

Identifying and validating causal genetic alterations in human breast cancer.

An important mechanism for the activation of proto-oncogenes in human breast and other cancers is gene amplification, which results in gene overexpression at both the message and the protein levels. Recent studies have demonstrated that oncogenes rarely if ever become amplified in isolation, but rather are present on large amplicons that contain multiple genes. More detailed analysis of these amplicons has revealed the presence of many candidate breast cancer oncogenes. The broad goal of this issue of Breast Cancer Research and Treatment is to review the current state of our understanding of the causal role of defined genetic alterations that occur in human breast cancers, and to discuss the case for the mechanistic significance of several candidate oncogenes. As will be seen, these studies have revealed a remarkable genetic complexity and heterogeneity in human breast cancer that must be dissected in order to improve our mechanistic understanding of disease progression, and to develop effective new drugs against relevant molecular targets.

Breast Neoplasms↗

PubMed1998

Teacher discipline and child misbehavior in day care: untangling causality with correlational data.

Day-care centers provide an ideal, underused setting for studying the developmental processes of child psychopathology. The influence of day-care teachers' lax and overreactive discipline on children's behavior problems was examined, as was the influence of children's behavior problems on teachers' discipline. Participants were 145 children and 16 day-care teachers from 8 classrooms in a day-care center for children from low-income families. Two techniques are presented for estimating causal relations based on correlational data gathered from day-care centers: 2-stage least squares and simultaneous structural equation modeling. Across techniques, teachers' laxness strongly influenced child misbehavior, and child misbehavior influenced both teachers' overreactivity and laxness. Teachers' overreactivity did not influence child misbehavior

Adult↗

PubMed1998

The development of bases for trait attribution: children's understanding of traits as causal mechanisms based on desire.

Two studies investigated 4- to 7-year-old children's understanding that traits can be causal mechanisms based on desires, as well as mere summaries of behavioral regularities. In Experiment 1, children made predictions given trait information. Children from 5 years made different emotion predictions about the same situation for actors with different traits, thus appreciating traits as psychological causes. For behavior prediction, children over age 4 generalized across situations. In Experiment 2, accurate emotion prediction by 3- to 7-year-olds was linked to understanding desire as a subjective mental property. The results suggest that children change from viewing traits as behavioral regularities to understanding them as internal mediators, and that advances in understanding desire underlie this change. These changes in understanding traits extend research on theory of mind beyond the basic concepts of desire and belief.

Adult↗